2010-LAB Packet-6101

2010-LAB Packet-6101 - PHCY 6101 Practical Aspects of...

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Unformatted text preview: PHCY 6101 Practical Aspects of Dosage Form Design Fall 2010 LAB Packet School of Pharmacy University of Wyoming Instructor: M. Glaucia Teixeira Dose Form Lab PHCY 6101-2010 Contents Course Schedule.................................................................................................................. iii LABORATORY 1 .................................................................................................................... 1 INTRODUCTION TO LABORATORY .............................................................................. 1 Safety in the laboratory ..................................................................................................... 1 Safety Rules ...................................................................................................................... 1 Weighing and Maintenance of balances and stir/hot plates .............................................. 3 Hand washing test ............................................................................................................. 3 Washing/cleaning supplies................................................................................................ 4 LABORATORY 2 .................................................................................................................... 5 PHARMACEUTICAL MEASUREMENTS ........................................................................ 5 Measurement of Solids ..................................................................................................... 5 Measurement of Liquids ................................................................................................... 9 LAB EXERCISES .......................................................................................................... 11 LABORATORY 3 .................................................................................................................. 14 POWDERS & GRANULES ............................................................................................... 14 Laboratory Exercise 1: Prickly Heat Dusting Powder .................................................... 16 Laboratory Exercise 2: Granules (for tablet preparation) ............................................... 18 LABORATORY 4 .................................................................................................................. 19 CAPSULES & TABLET TESTING (USP) ....................................................................... 19 Instructions for Lab Workflow ....................................................................................... 21 Laboratory Exercises: evaluation of uncoated compressed tablets................................. 22 Laboratory Exercise 1: Glucosamine Capsules .............................................................. 23 (Punch or hand filling method) ....................................................................................... 23 Laboratory Exercise 2: Acetylsalicylic Acid Capsules ............................................... 25 (Hand-operated filling machine) ..................................................................................... 25 LABORATORY 5 .................................................................................................................. 27 OINTMENTS & MEDICATED STICKS .......................................................................... 27 Laboratory Exercise 1: Hydrocortisone ointment – Incorporation method.................... 28 Laboratory Exercise 2: Benzoyl peroxide ointment (for cold sores and lip................ 29 irritations) – Fusion method ............................................................................................ 29 Laboratory Exercise 3: Beeswax lip stick with sunscreen (SPF 15) (lip protectant with sunscreen) – Fusion method ................................................................................... 30 LABORATORY 6 .................................................................................................................. 31 CREAMS, LOTIONS & PASTES ..................................................................................... 31 Laboratory Exercise 1: Cold Cream, USP (w/o emulsion base; fusion method)............ 32 Laboratory Exercise 2: Calamine Lotion, USP.............................................................. 33 Laboratory Exercise 3: Zinc Oxide Paste (astringent and protectant; used for diaper rash and bed sores; incorporation method) ................................................................ 34 LABORATORY 7 .................................................................................................................. 35 GELS & GUMMY LOZENGES ........................................................................................ 35 Laboratory Exercise 1: Piroxicam Alcoholic Gel ...................................................... 37 (topical non-steroidal anti-inflammatory gel) ................................................................. 37 Laboratory Exercise 2: Benzocaine Topical Gel (local anesthetic) ................................ 38 i Dose Form Lab PHCY 6101-2010 Laboratory Exercise 3: Gummy Gel Lozenges (for sore throat) .................................... 39 LABORATORY 8 .................................................................................................................. 41 SUPPOSITORIES .............................................................................................................. 41 Laboratory Exercise 1: Vaginal Progesterone suppositories .......................................... 43 Laboratory Exercise 2: Rectal Acetaminophen suppositories (children size) ................ 44 LABORATORY 9 .................................................................................................................. 45 SOLUTIONS ...................................................................................................................... 45 Laboratory Exercise 1: Mouthwash/Gargle (local antiseptic) ........................................ 47 Laboratory Exercise 2: Phenobarbital 0.4% Oral Solution ............................................. 47 Laboratory Exercise 3: Metoprolol Tartrate 10 mg/mL Oral Liquid .............................. 48 LABORATORY 10 ................................................................................................................ 49 SYRUPS ............................................................................................................................. 49 Laboratory Exercise 1: Promethazine Syrup (compare to Phenergan Syrup™) ........... 50 Laboratory Exercise 2: Acetaminophen Syrup (similar to Children’s Tylenol® suspension, liquid, or elixir)............................................................................................ 51 LABORATORY 11 ................................................................................................................ 53 ELIXIRS & TINCTURES .................................................................................................. 53 Laboratory Exercise 1: Terpin Hydrate and Dextromethorphan Elixir (expectorant & antitussive) .............................................................................................. 54 Laboratory Exercise 2: Hyoscyamine Elixir ................................................................ 55 Laboratory Exercise 3: Iodine Tincture (local anti-infective agent) .............................. 55 LABORATORY 12 ................................................................................................................ 57 SUSPENSIONS .................................................................................................................. 57 Laboratory Exercise 1: Magic Mouth Wash (for stomatitis) ......................................... 58 Laboratory Exercise 2: Ethylaminobenzoate topical suspension (similar benzocaine content as in Anbesol® ointment) ................................................................. 59 LABORATORY 13 ................................................................................................................ 60 EMULSIONS...................................................................................................................... 60 Laboratory Exercise 1: Trimethoprim and Sulfamethoxazole emulsion (compare to Septra® susp.) ............................................................................................... 61 Laboratory Exercise 2: Mineral Oil emulsion, USP (or Liquid Petrolatum emulsion)-employed as lubricating cathartic. ................................................................. 62 LABORATORY 14 ................................................................................................................ 63 Final Exam: ..................................................................................................................... 63 Lab check-out.................................................................................................................. 63 ii Dose Form Lab PHCY 6101-2010 Course Schedule Aug. 24,25, 26 LAB 1: Intro to Lab & Check in Aug.31, Sept. 1, 2 LAB 2: Pharmaceutical measurements Sept. 7,8, 9 LAB 3: Powders & Granules Sept. 14,15, 16 LAB 4: Capsules & Tablet testing (USP) Sept. 21,22, 23 LAB 5: Ointments & sticks Sept. 28,29, 30 LAB 6: Creams & Pastes; QUIZ 1 Oct. 5,6, 7 LAB 7: Gels & Lozenges Oct. 12,13, 14 LAB 8: Suppositories Oct. 19,20, 21 LAB 9: Solutions; QUIZ 2 Oct. 26,27, 28 LAB 10: Syrups Nov. 2,3, 4 LAB 11: Elixirs & Tinctures Nov. 9,10, 11 LAB 12: Suspensions Nov. 16,17, 18 LAB 13: Emulsions; QUIZ 3 Nov.30, Dec. 1,2 LAB 14: FINAL EXAM & Lab check-out Oct.25-29: Nov.24-26: Course schedule Advising Week for Spring 2011 (sign-up list for advising and class schedule forms available at your advisor's office door during previous week) Thanksgiving Break – no classes iii PHCY 6101- Dose Form Lab Fall 2010 LABORATORY 1 INTRODUCTION TO LABORATORY Safety in the laboratory • • • Please take 5 minutes and review the safety rules listed below. The instructor will show the location of and demonstrate the use of safety supplies within the laboratory. Clarification on UW Safety Office requirement for use of lab jacket, goggles, gloves, masks. Safety Rules The School of Pharmacy and the University of Wyoming are committed to provide to all students a safe, clean and efficient environment in which to learn and work. This document describes the hazards to which students might be exposed during laboratory exercises and provides operational procedures to safeguard the students. 1. A copy of the UW Environmental Health & Safety Manual can be obtained through http://www.uwyo.edu/safety/ click on Safety Manual pdf. The Environmental Health and Safety Manual is the official document for dealing with health and safety of students and employees at the University of Wyoming. 2. There will be an official introduction to lab safety rules, use of equipment, and discussion on general techniques that will be used during labs. 3. The laboratory is equipped with all required safety devices (eyewash fountains/bottles, hand wash sink, fire extinguishers and waste disposal containers for glass and sharps). 4. Appropriate disinfectant solutions, paper towels, a dustpan, broom and squeegee are available for spills of non-infectious/non-caustic materials. All clean-up procedures will be performed by instructor or TA. LAB 1: Intro & Check-in 1 PHCY 6101- Dose Form Lab Fall 2010 5. Lab coat (clean!) and eye protection must be used at all times during laboratory exercises. Additionally, whenever necessary, the use of masks and disposable gloves (provided by the School of Pharmacy) will be suggested by the instructor. 6. There is a pre-lab lecture before all laboratory exercises devoted to instruction about safe handling, use and techniques to follow. 7. Chemicals used during the laboratories are mostly salts, weak acids or weak bases, or very dilute solutions of drugs, regularly used in humans and exposition to chemical hazards extremely reduced and contamination very unlikely. Thus, the use of fume hoods is not necessary. However, all chemicals may pose unknown hazards and should be used with caution. Safe handling methods which are in keeping with good laboratory practice are expected. 8. Hand washing is highly recommended and emphasized whenever the hands get in contact with any of these agents. 9. Biologicals, blood and blood products, and infectious materials (human body fluids, human tissue) will not be handled in this lab. 10. According to the concept of universal precautions by OSHA (Occupational Safety and Health Administration), all human blood and body fluids should be assumed to be contaminated with Hepatitis B, HIV and/or other blood-borne pathogens. However, risk of exposure to blood-borne pathogen during this class is basically inexistent. If any accidental cuts or abrasions happen, the student will stop the procedure and, with the help of instructor, clean injured area and use recommended first aid measures. First aid kits for this class are placed nearby all sinks in Rm. 381(these will not be used by this class) and in a cabinet above hand washing sink in Rm. 379. If bleeding is unstoppable, the student will be directed to the Student Health Building. Students should not help with cleanup and first aid measures on another student to avoid contact with anyone else’s blood or blood-contaminated material. Only the instructor is in charge of first aid measures in the lab. 11. Splashing of any materials to face, eyes, mouth, etc, should be immediately washed with tap water and the eyewash if necessary. 12. Containers for glass disposal and puncture-resistant containers for sharps are available in the lab. 13. Eating, drinking, smoking, applying lip balm, handling contact lenses, etc, are prohibited in any room of the Pharmaceutical Care Learning Center, including pre-lab room and conference room. • These safety rules are part of the PHCY 6101 course packet for Dose Form laboratory and the instructor expects all students to follow them accordingly. LAB 1: Intro & Check-in 2 PHCY 6101- Dose Form Lab Fall 2010 Weighing and Maintenance of balances and stir/hot plates • • • • • Each student will be issued a stir/hot plate and a pharmaceutical grade torsion balance (numbered), which must be kept clean at all times. No chemicals should be left on top of pans of balance and top of stir plates to prevent corrosion and smoke. Both pieces of equipment will be shared by two other students registered in other sections of this lab. Numbered boxes of weights (for torsion balance) and small forceps (to handle balance weights) are available in a labeled drawer in the lab center island. Weights must be kept in box to prevent losing. Seven (7) electronic balances, labeled A through F, are available to be used during most labs (determined by instructor) and a list of students responsible to clean them during each lab is posted in the pre-lab room and in the lab-next to the key cabinet. Balance cleaning must be followed and are part of the lab grade for those students assigned. During Lab 2 the instructor will demonstrate basic principles related to the lab’s electronic balances and how to use and clean them. Most weighing will be performed using weighing paper unless weighing boats are recommended by the instructor (e.g. sticky chemicals, large amounts, etc). Hand washing test Hand washing can prevent personnel-transmitted infections. Before compounding, personnel should scrub hands and arms to the elbows with an appropriate cleanser. Hand washing is sometimes incorrectly omitted when gloves are worn, the assumption being that they provide enough protection. In fact, microorganisms multiply rapidly inside warm moist gloves and then can leak through them. The leakage rate is more than 50% when gloves are stressed during use. For this reason, the Centers for Disease Control and Prevention (CDC) and the USP have stated that gloving does not replace hand washing and that hand washing is imperative after gloves are removed. Compliance with hand washing by medical personnel is multifaceted. It is affected by individual motivation, knowledge of hand washing importance, staffing, location of sinks, supply of paper towels/dryers, conditions of employee's hands, and general enforcement policies. Ironically, it is considered the single most important procedure for preventing nosocomial infections (infections originating in a hospital or developing among hospital staff). Hand washing test: the instructor will distribute some drops of GloGerm® product into one hand of each student. The students will be asked to rub it into the other hand including on top of hands. With the help of water, soap and sponge/brush, students will try to remove as best as possible all bright orange color from their hands. Hands must be dried with paper towels before testing the hand washing quality with the UV lamp. LAB 1: Intro & Check-in 3 PHCY 6101- Dose Form Lab Fall 2010 Suggested hand washing procedure for all healthcare personnel and people handling food: 1. 2. 3. 4. Remove all jewelry, such as rings and watches Wet hands and forearms thoroughly Scrub hands vigorously with an antibacterial soap Work soap under the fingernails by rubbing them against the palm of the other hand 5. Interlace the fingers and scrub the spaces between the fingers 6. Wash wrists and arms up to the elbows 7. Thoroughly rinse the soap from hands and arms 8. Dry hands and forearms using a non-shedding paper towel 9. Use a dry paper towel to turn off the water faucet 10. After hands are washed, avoid touching clothes, face, hair, or any other potentially contaminated object in the area. Washing/cleaning supplies • • • • • • Use a piece of colored tape to write your name and apply it to your goggles/eye protector (for return in case you leave it out of your drawer). Using sponge, brush and SOS pad wash well with soap and hot water all beakers, cylinders, glass rod, mortars and pestles, spatulas and evaporation porcelain casserole. Dry with paper towel. Shake cylinders to remove the majority of the water. Wash all glassware also in the same manner after each laboratory exercise so you will be ready for the following lab. Place a piece of “butcher’s” paper as a lining on drawer and locker to keep glassware clean. Keep your eye protector in a zip bag so it doesn’t get scratched. Keep your lab coat clean so you look “presentable” and professional. If you take your coat home to wash and forget it, please let the instructor know before the beginning of the lab so a coat can be provided to you temporarily for that lab. In accordance to UW safety regulations no student will be allowed to participate in lab exercises without appropriate garb (coat and eye protector). LAB 1: Intro & Check-in 4 PHCY 6101- Dose Form Lab Fall 2010 LABORATORY 2 PHARMACEUTICAL MEASUREMENTS Objectives Introduction to the use of prescription balance class III (formerly class A) Learn how to determine the sensitivity requirement of a prescription balance Practice the use of the prescription balance and use of the Aliquot method Practice measurements of liquid chemicals: correct use of graduate cylinders, pipettes, and calibration of a medicine dropper. References: Remington's (18th edition): pp 69-82. Pharmaceutical Dosage Forms and Drug Delivery Systems: H. Ansel, N. Popovich and L. Allen, 8th edition (2005), Appendix C, pp 685-695. Measurement of Solids CHARACTERISTICS OF THE PRESCRIPTION BALANCE Although the mortar and pestle are commonly used as a symbol of pharmacy, the ever-present (required by law) prescription balance could as appropriately represent pharmacy. As the prescription balance is used daily to weigh vital medicinal agents, it is imperative that the pharmacist completely understands its characteristics and correct usage. Prescription balances are termed class III (formerly class A) balances, which meet the prescribed standards of the National Institute of Standards and Technology. The sensitivity of a balance is usually referred to as the sensitivity requirement (SR), which is defined as the maximum change in load that will cause a specified change, one subdivision on the index plate, in the position of rest of the indicating element of the balance. Prescription balances have a SR of 6 mg with no load and with a load of 10 g on each pan. The smaller the weight required moving the indicator one subdivision, the more sensitive is the balance. Most class III prescription balances have a maximum capacity of 120 g and bear a statement to that effect. If no information is given, the nominal capacity of a prescription balance is assumed to be 15.5 g. The prescription balance class III comes with a set of analytical weights, which meet the National Bureau of Standards’ specifications for analytical weights. These weights LAB 2: Pharmaceutical measurements 5 PHCY 6101- Dose Form Lab Fall 2010 consist of one 50-g, one 20-g, two 10-g, one 5-g, two 2-g, one 1-g, one 500-mg, two 200-mg, one 100-mg, two 20-mg, one 10 -mg, and one 5-mg weight. Balances with similar SR of a prescription balance should be used for all weighing operations required in prescription compounding. The USP directs that to avoid weighing errors of 5% or greater, which may be due to the limit of accuracy of the prescription balance, one must weigh a minimum of 120 mg of any substance in each weighing (5% of 120 mg being the 6 mg SR, or error inherent with the balance). If a smaller weight of material is desired, it is directed that the pharmacist mix a larger calculated weight of the ingredient (120 mg or more), dilute it with a known weight of an inert dry diluent (as lactose), mix the two uniformly, and weigh an aliquot portion of the mixture (again 120 mg or more) calculated to contain the desired amount of agent. The class III balance with a capacity of 120 g should be used for all weighing required in prescription compounding. Electronic balances are available in various sensitivities. The one most commonly used in prescription compounding has a readability of 0.001 g; consequently, the least amount that can be weighed is 20 times that, or 20 mg. Electronic balances are much faster and easier to use than prescription balances. The digital readout is easy to read and the balance is quite versatile and easy to clean, and it has a relatively small footprint. LEVELING OF THE BALANCE The prescription balance should always be kept in a well-lighted location, placed on a firm, level counter approximately waist-high to the operator. The area should be as free from dust as possible and in an area that is draft-free. When not in use, the balance should always be kept with the weights off and the beam in the fixed or locked (arrested) position. Before weighing the balance must be made level. This is accomplished with the leveling screws on the bottom of the balance. The arrest knob must be released (unlocked) and the balance adjusted to obtain equal swings of the pointer level to the right and left or up and down (depending on the type of balance) or to obtain stoppage or rest with exact alignment of the pointer. The rider on the graduated beam or the indicator of the dial on the front panel (depending on the type of balance) must be at its zero position at all times during operations. • Arrest knob turned right = locked or arrested position • Arrest knob turned left = unlocked or released position DETERMINATION OF THE SENSITIVITY REQUIREMENT The National Formulary (NF) calls for a sensitivity requirement of 6 mg for a prescription balance. This could be determined by the following procedure: 1. Level the balance and determine the rest point. The balance lid is to be closed to prevent drafts from affecting the oscillations. 2. Place a 6-mg weight on the right pan. The rest point should not shift less than one division on the indicator scale. 3. Level the balance and determine the rest point with a 10-g weight in the center of each pan. 4. Place a 6-mg weight on the right pan. The rest point should not be shifted less than one division. LAB 2: Pharmaceutical measurements 6 PHCY 6101- Dose Form Lab Fall 2010 Since few, if any, set of weights include a mass of less than 10 mg, the following practical procedure is suggested to determine the sensitivity requirement in the laboratory: 1. Level the balance and determine the rest point. The balance lid is to be closed to prevent drafts from affecting the oscillations. 2. Record the number of scale divisions the index pointer is shifted by a 20-mg and a 10-mg weight. In some balances you may have to use a combination of 10, and 5mg weights. 3. Plot the weight against the number of scale divisions shifted by each weight on a graph paper. 4. Draw a straight line through the points, and from the straight line read the weight that will cause a shift of one scale division. 5. Repeat with a 10-g weight on each pan. USE OF THE PRESCRIPTION BALANCE The pharmacist must not only maintain a proper prescription balance, but he must employ the correct weighing technique and be conscious of the limitations of the balance for the particular quantity of drug to be weighed. Medicinal substances are weighed on powder papers or weighing dishes/boats. The paper/dish protects the pans from chemical action and eliminates the need for repeated washing of the pans. A new paper/dish for each item prevents contamination. Another advantage to utilizing a paper/dish is that it serves as a transfer funnel. Weighing papers should have a glazed surface or should be made of aluminum foil so that no appreciable amount of the drug will adhere to the paper. This is especially important when small quantities are to be weighed. A paper should be chosen so it is of reasonable size giving a maximum weighing area without touching any part of the balance except the pan. The papers should be creased diagonally from one corner to the opposite corner or the edges turned up (aluminum foil) before placing on the pans. If desired, tared watch glasses or small beakers may be used on the balance pans instead of papers. WEIGHING TECHNIQUE In using a prescription balance, neither the weights nor the substance to be weighed should be placed on the balance while the beam is free to oscillate. Usual guidelines to weighing technique are: 1. Before weighing, powder papers of equal size should be placed on both pans of the balance and the equilibrium of the balance tested by releasing the arresting knob. If the balance is off because of differences in the weight of the powder papers, small tearings of powder paper must be added to the light pan. Powder papers taken from the same box can vary in weight by as much as 65 mg. If balance equilibrium is not established after the papers are placed on the pans, an error of more than 30% can result in weighing 200 mg of material. 2. When balanced (index pointer is at zero), the balance is placed in the arrested position, the lid is opened and the desired weights added to the right-hand pan and/or the weigh beam. LAB 2: Pharmaceutical measurements 7 PHCY 6101- Dose Form Lab 3. 4. 5. Fall 2010 An amount of substance considered to be approximately the desired weight is carefully placed on the left hand pan with a spatula and the lid closed. The arrest knob should then be slowly released to check the equilibrium. The arresting knob is most conveniently operated by the left hand. If the substance is in excess, the balance is arrested again and a small portion of the substance removed with the spatula. The same procedure is used if more substance is needed. A pharmacist should always remember that when a stated quantity of a substance was weighed, this includes not only the true weight but also the possible excessive or deficient weight by virtue of the sensitivity of the balance. Knowing the sensitivity of the balance, one may calculate the percent of possible error for a given amount to be weighed. For example, assume that 5 mg produce a change of one index plate division in the rest point and 200 mg of drug is to be weighed, the actual weight could be between 195-205 mg. The percentage of possible error is calculated by the ratio, 5 mg X% = 200mg 100% producing a value of X = 2.5%. Thus, the inherent percentage of error for any given situation may be expressed as, Percentage of Error = Sensitivity Requirement X 100 Quantity Desired The same relationship may be used to calculate the smallest amount that can be weighed within a particular permissible percentage of error. Assuming the sensitivity requirement of a balance is 5 mg and the permissible percentage of error is 5%, one may calculate the smallest quantity that can be weighed within this limit or error. A ratio is set up as before, 5mg 5% = xmg 100% and will produce a value of X = 100 mg. Thus, the smallest amount that can be weighed with a certain permissible percent or error may be expressed as Smallest quantity to be weighed = _____SR X 100_______ Permissible Percent of Error In order to achieve 99% accuracy, that is, to permit a 1% error, the amount weighed must be at least 100 times as great as the sensitivity requirement of the balance. To achieve 90% accuracy or to allow a 10% error, one must weigh at least 10 times as much as the sensitivity requirement of the balance. LAB 2: Pharmaceutical measurements 8 PHCY 6101- Dose Form Lab Fall 2010 ALIQUOT METHOD When the amount of drug is too small to be weighed directly on the prescription balance (<120 mg), the aliquot method of weighing is used. An aliquot part is defined as any part that is contained a whole number of times in a quantity; e.g. 2 is an aliquot of 10, since 10/2 = 5, 2 is referred to as the fifth aliquot of 10. Also, 2 mg of drug uniformly dispersed in exactly 98 mg of diluent represents a fifty-fold dilution. 1. 2. 3. To use the aliquot method in compounding, follow three steps: Weigh a multiple of the quantity desired (prescription balance). Dilute the multiple in a suitable manner. Weigh or measure an aliquot of the final mixture (dilution). Example 1: Suppose the smallest amount of drug that we can weigh on a Prescription Balance is 100 mg, but we need only 20 mg. Procedure is to weigh out 100 mg of drug (which is multiple of 20 mg). We then dilute it with 900 mg of lactose to make a total of 1000 mg (1 g). This 1000 mg of mixture contains 20 mg of drug in each 200 mg. We can now weigh out 200 mg of mixture (fifth aliquot of 1000 mg) and it will contain 20 mg of the drug. Example 2: A pharmacist needs 60 ml of silver nitrate solution 1:5000. For the above preparation we need 1000 mg x 60 ml = 12 mg AgNO 3 5000 ml The procedure is to weigh out 120 mg AgNO3 and dissolve it in distilled water. The volume is made up to 100 ml. This will give a 1.2 mg/ml solution. 10 ml of this solution should be measured and diluted to 60 ml. Measurement of Liquids In pharmacy, measuring of liquids should be done by selecting the measuring device most appropriate to the volume of liquid to be measured and the desired degree of accuracy. With liquids, the more narrow the column of liquid, the more accurate is likely to be the measurement. Many types of devices are used in this operation, depending on the kind and quantity of liquid to be measured. The three most important devices used in liquid measurement in pharmacy are graduated cylinders (or cylindrical graduates), pipettes (pipettes) and droppers. Cylindrical graduates are generally calibrated in metric units and are available in a wide variety of capacities, ranging from 5 to 1000 mL or more. In measuring small volumes, less than 1.5 mL, the pharmacist should use a pipette and a pipette filler (pipette helper), which will also allow accurate delivery of the liquid. The LAB 2: Pharmaceutical measurements 9 PHCY 6101- Dose Form Lab Fall 2010 pharmacopeial medicine dropper is used for measuring small quantity of liquid. The dropper is constricted at the delivery end to a round opening having an external diameter of 3 mm. A vertically positioned pharmacopeial medicine dropper delivers a drop of water weighing between 45 and 55 mg. In using droppers the pharmacist must realize that a drop is not a unit of volume as the volume of a drop delivered from the same dropper depends on different factors. For a given dropper, the volume of a drop varies as a function of the pressure applied and the temperature, and as the function of the density, viscosity, and surface tension of the liquid delivered. To maintain accuracy, one must remember the position of the dropper while pouring the drop. Errors in measuring may be made by the operator if he tilts the measuring device or fails to align the graduation mark and the bottom of the meniscus (meniscus = concave or crescent shaped surface of liquid that bulges downward). This is known as parallax effect. Parallax is the apparent displacement of an object that follows a change in the position from which it is viewed. This phenomenon may cause measuring errors larger than 5%, which are unacceptable from a pharmaceutical point of view. To avoid this error, the graduate/other device is raised and held straight up so that the graduation point to be read is on a level with the eye, keeping the brown surface (if any) towards the back, and the liquid is measured. LAB 2: Pharmaceutical measurements 10 PHCY 6101- Dose Form Lab Fall 2010 In using graduates, the pharmacist pours the liquid into the graduate slowly, observing the level. In measuring viscous liquids, adequate time must be allowed for the liquid to settle in the graduate, as some may run slowly down the inner sides of the graduate. It is best to attempt to pour such liquids toward the center of the graduate, avoiding contact with the sides. In emptying the graduate of its measured contents, adequate drain time should be allowed. When pouring liquids from bottles, good pharmaceutical technique is to keep the label on the bottle facing up; this avoids the possibility of any errant liquid running down over the label as the bottle is righted after use. The bottle orifice should be wiped clean after each use. Prescriptions consisting of several liquids should not be compounded in prescription bottles, but they must be accurately measured in a suitable graduate and then transferred into graduated or un-graduated prescription bottles. The graduations in the prescription bottles are usually very inaccurate. LAB EXERCISES Exercises using the torsion/prescription balance: 1. Obtain a box with a standard set of weights (in a drawer of the lab center island) with a number that matches your balance number. Determine the sensitivity requirement (SR) of your balance twice. 1)Using a 20-mg and a 10mg weight. Record the number of scale divisions the index pointer is shifted. Plot the weight against the number of scale divisions shifted by each weight on a graph paper (provided). Draw a straight line (as best as possible) through both points, and from the straight line read the weight that will cause a shift of one scale division, if needed. 2) Repeat the same procedure and graphing with a 10-g weight on each pan. 2. Fill one medium size weighing boat with charcoal and one with lactose and bring to your bench. Using the aliquot method or the least weighable amount method (consider USP-approved error and SR) prepare the following charcoal dilution (trituration), have it checked by the instructor or TA and discard the mixture into trash can. Return unused charcoal and lactose to original containers. Do not mix spatulas and try to not contaminate one chemical with the other. ℞ Sig. Charcoal 25 mg Lactose q.s. 2g Mix and make trituration Instructions: a) Use glass mortar and pestle and plastic spatulas (to help fluffing the powders as you mix them). b) Prepare a dilution to allow an aliquot to contain the required amount of charcoal in lactose, avoiding excessive waste of unused dilution (trituration). c) In preparing the dilution to obtain the required aliquot, start with weighed amount of charcoal. When mixing a small amount of drug (mg level) with a large amount LAB 2: Pharmaceutical measurements 11 PHCY 6101- Dose Form Lab Fall 2010 of a second ingredient, the drug is placed in the mortar with equal bulk of the other ingredient. The two ingredients are triturated until intimately mixed. Then, an equal bulk of the second ingredient is added to the mixture, and the powders are triturated until intimately mixed. The material is triturated by geometric addition until all gone. This method is known as geometric dilution. d) Get dilution checked by instructor/TA for homogeneity. e) Weigh out the aliquot and the additional lactose required to complete the Rx amount prescribed. f) After final Rx is completely mixed, get it checked by instructor/TA for homogeneity and discard into trash cans. Exercises using electronic balances: 3. Perform the following weighing operations using electronic balances. a. Weigh 0.5 g (gram) of dextrose. Ask instructor/TA to check the amount weighed. Return weighed powder to original container. b. Weigh 50 mg of dextrose, by instructor/TA, return to container. Exercises using glass cylinders: 4. Fill a large beaker available in your locker with tap water. Perform on your bench all of the following measurement operations and get all measured volumes checked at the same time by instructor/TA. Discard checked volumes in sink. a. Using 10-mL cylinder measure 2.5 mL of water. b. Using 25-mL cylinder measure 12 mL of water. c. Using 50-mL cylinder measure 28 mL of water. d. Using 100-mL cylinder measure 56 mL of water. Calibration of a prescription bottle: 5. Obtain one 3-ounce prescription bottle and fill with tap water to the 90-ml mark. Transfer the contents of the bottle to a 100-ml cylindrical graduate. Record the volume. Observe the difference between both measurements. Return the prescription bottle separated from cap to the container on the counter. Exercises using pipettes: 6. Using pipettes, pipette helpers, and liquids provided on top of center island in lab, perform the following measuring operations and get the measured volumes checked by instructor/TA. a. Using a 5-mL pipette measure 2.7 mL of water, by instructor, discard into large container provided. b. Using a 10-mL pipette measure 4.5 mL of water, by instructor, discard into large container provided. c. Using a 10-mL pipette measure 5.7 mL of alcohol, by instructor, discard into the bottle provided. Exercises using droppers: 7. Obtain one disposable “dropper” (transfer pipette) and get your 10-mL cylindrical graduate. Using droppers, and liquids provided on top of center island in lab, perform the following measuring operations: a. Holding a medicine dropper vertically, count and record the number of LAB 2: Pharmaceutical measurements 12 PHCY 6101- Dose Form Lab Fall 2010 drops of water required to fill a 10-ml cylindrical graduate to the 3-ml mark. b. Repeat the previous measurement holding the dropper at a ~20-30° angle with the horizontal line. c. Holding a medicine dropper vertically, count and record the number of drops of alcohol required to fill a 10-ml cylindrical graduate to the 3-ml mark. 8. Measure glycerin using droppers attached to the glycerin containers. Holding a medicine dropper with a slight inclination, count and record the number of drops of glycerin required to fill a 10-ml cylindrical graduate to the 3-ml mark. Discard into sink by rinsing the graduate thoroughly (glycerin is water-soluble and harmless). 9. Prepare a 1% solution (10 ml) of sodium lauryl sulfate (use mask or handle powder slowly while weighing to prevent inhalation). a. Holding the dropper vertically, count and record the number of drops required to fill a 10-ml cylindrical graduate to the 3-ml mark. b. Heat the surfactant solution to 70° C (use thermometer to monitor the temperature, not to stir the solution). Using this warm solution, repeat the previous measurement. CALCULATIONS/RESULTS (to be submitted at the end of lab) At the end of lab submit on a sheet of paper all results, calculations, graphs, and performed measurements to the instructor/TA for grading (lab assignment = BONUS). Include your name, section (TUE, WED, THU), locker number and balance number. 1. 2. 3. 4. 5. Submit the graph paper with SR determinations. Include your name, section (TUE, WED, or THU), locker number and balance number. Submit the measurements (number of drops = gtt) performed with droppers (exercises 9, 10 and 11 above). Calculate the percent of error that would be incurred in measuring 50 mg of atropine sulfate using the balance on your work bench. If the permissible error of your torsion balance were 15%, which would be the minimum quantity of a drug that you could weigh accurately using it? Show calculations for the following compounding situation. A pharmacist needs 0.15 ml of flavoring oil (orange oil) to prepare an oral liquid. He has alcohol to be used as a solvent and only a 2 mL pipette with 0.2 ml graduations. How could this volume of orange oil be obtained? LAB 2: Pharmaceutical measurements 13 PHCY 6101- Dose Form Lab Fall 2010 LABORATORY 3 POWDERS & GRANULES Objectives Appreciate the versatility of powders and granules when used per se in therapeutics and in the preparation of other dosage forms. Learn to prepare a bulk powder for the medicinal value of its contents for external application. Learn to prepare agglomerates of powdered materials (granules) to be used for pharmaceutical purpose, such as in making tablets. Powder usually refers to a chemical or mixture of substances in the solid physical state. As a pharmaceutical preparation, powders are intimate mixtures of dry, finely divided drug(s) and/or inactive pharmaceutic ingredients that may be intended for internal (i.e. oral powder) or external use (i.e. topical powder). Bulk powders are usually non-potent and are dosed with measuring devices, such as a teaspoon, the cap of the container, a cup, etc. Dusting powders are fine powders intended to be dusted on the skin through a sifter top container. In general, a single medicinal agent is used as a dusting powder but frequently a base (inert powders) is used to protect the skin from irritation and friction. Powder bases absorb secretions and have a drying effect. Dusting powders should be passed through a fine mesh sieve to ensure that they are grit-free (to avoid mechanical irritation of traumatized areas) and well blended. Most powders for internal use are taken orally after mixing with water, a drinkable liquid, or soft food, and may be intended for local effects (e.g. laxatives) or systemic effects (e.g. analgesics). Other dry powders are packaged for reconstitution with a liquid solvent or vehicle (drug relatively unstable in liquid form), for oral, parenteral (injections) or vaginal administration (douches). Some powders are also intended to be inhaled for local and systemic effects, and are dispensed in metered inhalation aerosols. Granules are prepared agglomerates of smaller particles of powder. They are irregularly shaped but may be prepared to be spherical. They are usually in the 4- to 12-sieve size range, although granules of various mesh sizes may be prepared depending upon their application: granules for constitution or for mixture with beverages or sprinkled on food, granules for encapsulation, effervescent granulated salts, and granulation to be compressed into tablet form. Lab 3: POWDERS & GRANULES 14 PHCY 6101- Dose Form Lab Fall 2010 Granules are usually formed by moistening blended powders and passing through a screen or a special granulator. These moist granules are either air or oven dried. For drug products with a bitter or salty taste, effervescent granules may be prepared, consisting of mixtures of drug(s) with citric acid and/or tartaric acid and/or sodium biphosphate combined with sodium bicarbonate. Because of their flow properties, granulations are commonly used in tablet making to facilitate the free flow of material from the feeding container (or hopper) into the tablet presses. The three most used methods for the preparations of compressed tablets are: wet granulation method, dry granulation method, and direct compression. Wet granulation is probably the most common method employed for the production of compressed tablets of drugs not degraded by hydrolysis. The steps required in the preparation of tablets by wet granulation method may be separated as follows: (1) weighing and blending the ingredients, (2) preparing the wet granulation, (3) screening the damp mass into pellets or granules, (4) drying, (5) dry screening, (6) lubrication and blending, (7) tableting by compression. In the dry granulation method the granulation is formed not by moistening or adding a binding agent to the powdered drug mixture but by compacting large masses of the mixture ('slugging') and subsequently crushing and sizing these pieces into smaller granules by passing through a screen of desired mesh. Lubricants are added in the usual manner, and tablets are made by compression. For this method, either the active ingredient or the diluent(s) must have cohesive properties in order for the large masses to be formed. Direct compression, as the name implies, consists of compressing tablets directly from powdered material without modifying the physical nature of the material itself. General Lab Instructions: Sieves will be shared by students with neighboring lockers A spatula should be passed under the mesh to recover all granulation prepared. Sieves are NOT to be washed after use. Balance cleaning will be observed (and graded) starting this week. Lab 3: POWDERS & GRANULES 15 PHCY 6101- Dose Form Lab Fall 2010 Laboratory Exercise 1: Prickly Heat Dusting Powder Erasmus B. Dragon, MD 100 S. Main Street, suite 40 Laramie, WY 82070 Tel. (307) 742-1234 DEA # ___________ Rx Date: 9/8/2010 Anthony B. Stuart Prickly Heat Dusting powder: Talc Cornstarch Zinc oxide Fragrance (optional) M. Ft. 40 g Sig. Apply to affected area prn Refill – NR 1 2 3 4 prn 4.5 parts 4.5 parts 1 part 2-5 drops Erasmus B. Dragon M.D. Method 1. 2. 3. 4. 5. 6. Accurately weigh all ingredients required to prepare 40 g of medicinal powder. Add cornstarch, talc and zinc oxide to a zip bag, close zip closure and mix well. Since no pressure is applied to the mixture as it is blended, the resulting powder is light and fluffy. If a fragrance is desired, transfer ~2 mL of ethanol to a small beaker and add 2-5 drops of fragrance. Add this mixture to the zip bag and mix well. If clumps are present, use a household strainer to get rid of clumps before transferring the powder mix to a powder sifter container. Label product. Alternatively, this medicinal powder could be prepared as follows. a) Blend cornstarch and talc by spatulation on top of a piece of wax paper or ointment tile. b) Add cornstarch-talc mixture to zinc oxide using geometric dilution. c) Since pressure will be applied to the mixture as powders are blended, the resulting powder will require sifting to produce a light and fluffy product for dusting the skin. Note: No trituration (in mortar) is required to reduce particle size because all ingredients are very fine powders. Trituration would also require final sieving in order to remove clumps. Lab 3: POWDERS & GRANULES 16 PHCY 6101- Dose Form Lab Fall 2010 Labels Dewy Cheatham & Howe Pharmacy 9876 W. Broadway Greenplace, ZZ 12345 Tel. (777) 234-5678 Rx 1-MGT-Q12 Anthony B. Stuart Date: 9/8/2010 Dr. Erasmus B. Dragon, MD Prickly Heat Dusting powder, 40 g Apply to affected area of the skin for stinging and itching caused by prickly heat. Exp. 1 year (use actual date) Refills: 01 MGT (Preparer’s initials) For external use only Do not apply near nose or eyes Store in a dry place Keep out of reach of children Lab 3: POWDERS & GRANULES 17 PHCY 6101- Dose Form Lab Fall 2010 Laboratory Exercise 2: Granules (for tablet preparation) Granulation for the preparation of Acetaminophen 500 mg Compressed Tablets: (Wet Granulation Method) Each tablet contains: Acetaminophen Polyvinylpyrrolidone (K-15) Lactose Alcohol *Stearic Acid *Talc Starch 500 mg 35 mg 85 mg enough to dampen the powder mixture 13.3 mg 20 mg 35 mg + 35 mg* Make granulation enough to prepare 20 tablets. * These ingredients will not be used; do not weigh them! Method: 1. Blend acetaminophen, lactose and half of the starch on ointment slab using spatulation. Reserve. 2. Use ceramic casserole to disperse polyvinylpyrrolidone in alcohol using a plastic spatula to mix. 3. Add mixture prepared in ceramic casserole to powder mixture on ointment slab and combine well. Include an additional 2-3 ml (not to exceed 4 ml) of alcohol to dampen the powder mass appropriately. 4. Make granules by pressing the damp mass through a No. 8-mesh screen and collecting into a piece of wax paper. Do NOT rinse the sieve! 5. Transfer the powder to a piece of aluminum foil folded as a weighing dish and dry the granules in a drying oven for ~10-15 min at 150 °C (oven setting = 6). 6. Hand out the product in a 1 oz. container. Label the product with “Granulation for Acetaminophen 500 mg compressed Tablets”, your name, date, and desk number. When preparing tablets: 7. After drying, the granules are passed through a No. 18-mesh screen. 8. Talc, stearic acid and the other portion of starch are added to the granulation and the mixture is fed into the hopper of the tablet machine for tableting. Lab 3: POWDERS & GRANULES 18 PHCY 6101- Dose Form Lab Fall 2010 LABORATORY 4 CAPSULES & TABLET TESTING (USP) Objectives Understand the importance of tablets and capsules as the most common dosage forms. Prepare capsules using hand punch method and hand-operated filling machine. Perform some USP-designed tests for uncoated tablets to determine if they meet physical specifications and quality standards (weight variation, tablet thickness, tablet hardness and tendency to crumble (friability), and tablet disintegration). References: Remington's (21st edition, 2006), Ch. 45: Oral Solid Dosage forms, pp 889-928 Pharmaceutical Dosage Forms and Drug Delivery Systems: H. Ansel, N. Popovich and L. Allen, 8th edition (2005), Ch.7-8, pp .204-259. Capsules are solid dosage forms in which the drug substance is enclosed in either a hard or soft, soluble container of shell of a suitable form of gelatin. The gelatin used in the manufacture of capsule shell is obtained from collagenous material by hydrolysis. Capsules are tasteless, easily administered and easily filled either extemporaneously or in large quantities commercially. In prescription practice the use of hard gelatin capsules permits a choice in prescribing a single drug or a combination of drugs at the exact dosage level considered best for the individual patient. The hard gelatin capsule, also referred to as the dry-filled capsule, consists of two sections, one slipping over the other, thus completely surrounding the drug formulation. These capsules are filled by introducing the powder material into the longer end or body of the capsule and then slipping on the cap. Hard gelatin capsules are made largely from gelatin, FD&C colorants and sometimes an opacifying agent such as titanium dioxide. Capsules are supplied in a variety of sizes. The hard empty capsules are numbered from 000, the largest size that can be swallowed, to 5, which is the smallest. It is usually necessary for the pharmacist to determine the size of the capsule needed for a given prescription through experimentation. The experienced pharmacist having calculated the weight of material to be held by a single capsule, often will select the correct size immediately. If the material is powdered, the base of the capsule is filled and the top is replaced. If the material in the capsule proves Lab 4: Capsules & Tablet testing (USP) 19 PHCY 6101- Dose Form Lab Fall 2010 to be too heavy after weighing, a smaller size must be taken and the test repeated. If the filled capsule is light, it is possible that more can be forced into it by increasing the pressure. In prescription filling it is wise to check the weight of each filled capsule. When filling capsules on prescription, the usual procedure is to mix the ingredients by trituration, reducing them to a fine and uniform powder. Granular powders do not pack readily in capsules and crystalline materials are not fitted into capsules unless powdered. Eutectic mixtures that tend to liquefy may be dispensed in capsules if a suitable absorbent such as magnesium carbonate is used. Potent drugs given in small doses usually are mixed with an inert diluent such as lactose before filling into capsules. Usually the powder is placed on paper and flattened with a spatula so that the layer of powder is not greater than about 1/3 the length of the capsule which is being filled. This helps to keep both the hands and capsules clean. The cap is removed from the selected capsule and held in the left hand; the body is pressed repeatedly into the powder until it is filled. The cap is replaced and the capsule is weighed. In filling the capsule the spatula is helpful in pushing the last quantity of the material when the specified number of capsules has been packed. This condition is adjusted before dispensing the prescription. A variety of models of manual filling machines and automatic capsule-filling machine are available through numerous pharmaceutical compounding suppliers for increasing the speed of the filling operation. Many community pharmacists find this a useful piece of apparatus that is usually affordable. The most common solid dosage form in contemporary practice is a tablet, which may be defined a unit form of solid drugs prepared by compaction. A limited number of tablets are prepared by molding also. Compressed tablets are manufactured with tablet machines capable of exerting great pressure in compacting the powdered or granulated material through the use of various shaped punches and dies. In addition to the active or therapeutic ingredient, tablets contain a number of inert materials. The latter are known as additives or excipients. They may be classified according to the part they play in the finished tablet. The first group contains those, which help to impart satisfactory processing and compression characteristics to the formulation. These include diluents, binders, glidants, antiadherents and lubricants. The second group of added substances helps to give additional desirable physical characteristics to the finished tablet. Included in this group are disintegrants, colors, and in the case of chewable tablets, flavors and sweetening agents, and in the case of controlled release tablets, polymers or waxes or other solubility-retarding materials. Diluents add the necessary bulk to a formulation to prepare tablets of the desired size. Binders promote the adhesion of the particles of the formulation, enabling a granulation to be prepared and the maintenance of the integrity of the final tablet. Glidants enhance the flow of the tableting material into the tablet dies from the hopper. Antiadherents prevent the sticking of this material to the punches and dies. Disintegrants promote the breakup of the tablets after administration to smaller particles for more ready drug availability. Lab 4: Capsules & Tablet testing (USP) 20 PHCY 6101- Dose Form Lab Fall 2010 In addition to the apparent features, tablets must meet other physical specifications and quality standards. Quality standards and compendial requirements (USP) for tablets include criteria for: 1. Weight 2. Weight variation 3. Content uniformity 4. Thickness 5. Hardness 6. Disintegration 7. Dissolution Instructions for Lab Workflow 1) Lab experiments will be divided into two parts: filling of capsules and tablet testing. a) Students are divided into a Caps Group and Tab Group (list with groups will be posted on website and inside the lab). b) Each group is subdivided into small subgroups of 3-4 students each. c) Some activities will be done individually in its entirety, while others will be done as a subgroup. 2) Some balances are designated for tablet weighing only (balances D and E) and some are designated for capsule weighing only (balances A, B, C, F and G). This arrangement should be followed until a group (Tablet or Capsule group) finishes all assignments. The groups will then swap activities. 3) All materials and equipment required for use by each group are set: a) Near the balances and on center island (Tablet testing), b) On bench on south side of center island (Capsule filling), c) Capsule machines are placed on bench connected to south wall of lab. 4) Workflow: a) Tab subgroups will do tablet testing first, capsule hand fill second, and finally capsule machine fill. b) Caps subgroups will take turns doing capsule hand fill and machine fill and then go to tablet testing. 5) A sample example on how to prepare the label is provided by the instructor for Glucosamine capsules. Students will be responsible for preparing the label (+ recommended auxiliary labels) for ASA caps. Lab 4: Capsules & Tablet testing (USP) 21 PHCY 6101- Dose Form Lab Fall 2010 TABLET GROUP: ACTIVITIES a) Each student should initially identify his/her partners. b) Tablet testing activities will follow the steps described below (laboratory exercises). c) Using a weighing dish, each student will get 2 tablets (on center island) and start step 1 of evaluation of uncoated compressed tablets = weight variation. d) Each student will determine the tablet thickness of his/her 2 tabs (step 2) using hand gauge (calipers). e) All 3 or 4 students of each subgroup get their tablets placed together in the friabilator and with the help of a timer, get the tablets rotating for 3 minutes. After this time, tablets are removed from the drum using a pair of tweezers and weighed in one single step (step 3). Each student will get back 2 tabs for next step testing. f) Each student will determine the tablet hardness( breaking of tabs) of 2 tabs using a hand hardness tester (step 4). g) All students of a subgroup will get together and perform a disintegration test of 6 tablets (step 5). The disintegration machine allows two sets of 6 tabs to be tested at the same time. After disintegration of all 6 tablets is complete, the beakers must be emptied and re-filled with warm (~ 37°C) tap water up to 300-mL mark. Laboratory Exercises: evaluation of uncoated compressed tablets Perform all tests described below and present your results in a sheet of paper at the end of the lab (part of lab grade) 1. Use USP test and electronic balances to determine tablet weight variation (individual weight and average). Each student will select 2 tablets for a total of 68 tablets tested per subgroup. Compare your subgroup’s average results with 2 other subgroups and show calculations of weight deviation from each other (variation should be within 10% difference). 2. Using the same tablets from previous step, determine tablet thickness using a hand gauge (caliper) of all 6-8 tablets (each student determines 2 tabs). Compare your subgroup’s average results with 2 other subgroups. Show calculations. 3. Determine tablet durability or tendency to crumble (rate of abrasion) of the same 6-8 tablets, using a friabilator for 3 minutes (all 6-8 tablets added together to the acrylic drum). Weigh tablets after removing them from friabilator using tweezers. Calculate rate of abrasion by subtracting the new weight from the weight obtained in step 1. Compare the average rate of abrasion of your subgroup’s tablets with 2 other subgroups. Show calculations 4. Determine the hardness in kg (hand hardness tester) of the 6-8 tablets used in step 3 (2 tabs per student) and calculate the mean value. Compare your subgroup’s average results with 2 other subgroups. Show calculations. Lab 4: Capsules & Tablet testing (USP) 22 PHCY 6101- Dose Form Lab Fall 2010 5. Determine the time required to obtain complete disintegration of 6 new tablets. Compare your subgroup’s average results with 2 other subgroups. Show calculations. CAPSULE GROUP: ACTIVITIES a) Each student will get a piece of wax paper and hand fill Glucosamine capsules (clear capsules #00) individually, using the punch method described. b) Each student will weigh and blend the powders required to prepare a mixture enough to fill twenty (+2) Acetylsalicylic Acid capsules (caps # 1=prescription A or caps #4 = prescription B). i. Each student will use one of four hand-operated capsule filling machines. Students should come prepared to do either the #1 capsule prescription or the #4 capsule prescription (assignments to each group will be announced during lab) ii. Follow instructions for capsule filling posted near hand-operated machine. c) Each student will be required to clean the capsule machine with the help of a small brush after use. Laboratory Exercise 1: Glucosamine Capsules (Punch or hand filling method) Burt Keeley, MD 11123 Freemarket St. Johnston, FA 98765 Tel. (123) 9876-1234 Name: Address: Jonas Quick 123 Grand Ave. Laramie, Wyoming ℞ Glucosamine HCl Lactose M. ft. cap. d.t.d. no. 6 Sig: i cap bid Refills: 5 Date: 9/15/2010 600 mg q.s. Method 1. Gloves (or finger cots) are always required to hand fill capsules. High degree of cleanliness is also expected while handling the powder and the capsule shells. 2. Determine the capsule size and the quantity of lactose required to produce a proper capsule. a) Determine which size capsule will hold 600 mg of glucosamine HCl powder and completely fill it. If there is extra space in the capsule, then a diluent is needed. Lab 4: Capsules & Tablet testing (USP) 23 PHCY 6101- Dose Form Lab Fall 2010 b) Weigh the capsule filled with glucosamine HCl. c) Fill another capsule of the same size with the diluent and weigh. d) The quantity of diluent displaced (X) by the glucosamine HCl is determined by: weight of Gluc.HCl 600 mg = X weight of diluent e) Determine the quantity of diluent required to be added per capsule (Y) using: (Weight of diluent in capsule) – (X) = Y 3. For this laboratory exercise, it was determined that the capsule size will be No. 00 and it will require 600 mg glucosamine HCl + 300 mg lactose to completely fill each capsule. 4. Select 6 empty capsule shells (size #00). Accurately weigh the ingredients (+ one extra caps). 5. Thoroughly mix powders by spatulation on top of paper or ointment tile. 6. Given the small number of capsules to be filled, use the punch method. a) Using the spatula form the powder mix into a pressed cake having the depth of approximately ¼ to ⅓ the length of the capsule body. b) Holding an empty capsule body between the thumb and the forefinger add some powder with help of spatula then punch vertically into the powder cake repeatedly until filled. Gloves should be used to avoid handling the capsules with bare fingers. 7. Because the amount of powder packed into a capsule depends on the degree of compression, punch each capsule in the same manner and after capping, weigh the product to check the uniformity of the process. Weight of an empty capsule shell is ~ 110 mg. 8. After the body of a capsule has been filled and the cap placed on the body, the body may be gently squeezed or tapped to distribute some powder to the cap end and give the capsule a full appearance. 9. If filled capsule weight is correct (± 5% is acceptable by USP), seal body and cap with a Q-tip dipped in warm water. 10. Clean and polish capsules individually by rubbing with clean gauze. 11. Package filled capsules into a medicine bottle and label as needed. Dewey Cheetham & Howe Pharmacy 11123 Freemarket St. Johnston, FA 98765 Tel. (123) 9876‐1234 Rx 02-MGT-Q15 Dr. Keeley, Burt, MD Quick, Jonas Sept. 15, 2010 TAKE ONE CAPSULE BY MOUTH TWO TIMES A DAY Glucosamine hydrochloride 600 mg caps Qty: 6 caps Refills: 5 Exp.: 9/15/12 May cause softened stools Avoid shellfish while taking this medication Lab 4: Capsules & Tablet testing (USP) 24 PHCY 6101- Dose Form Lab Laboratory Exercise 2: A. Fall 2010 Acetylsalicylic Acid Capsules (Hand-operated filling machine) Burt Keeley, MD 11123 Freemarket St. Johnston, FA 98765 Tel. (123) 9876-1234 Name: Jerry Eastman Address: 123 Grand Ave. Laramie, Wyoming ℞ Date: Sept. 15, 2010 Acetylsalicylic Acid 200 mg Caffeine Citrate 40 mg Lactose, anhydrous q.s. Ft. Caps #20 (Content of each capsule= 360 mg) Sig: One cap p.r.n. pain. Not to exceed 4 caps/day. Refills: 2 Method 1. Weigh all ingredients required to fill 20 caps. 2. Use capsule size #1. 3. Use instructions available near capsule filling machine. 4. The weight of an empty capsule shell is ~75 mg. Use this information as tare for your filled capsules when verifying the uniformity of the encapsulation process (±5% is the acceptable error). Adjust powder as needed. 5. Dispense in container provided. 6. Label as required. B. Burt Keeley, MD 11123 Freemarket St. Johnston, FA 98765 Tel. (123) 9876-1234 Name: Jane Doe Address: 123 Grand Ave. Laramie, Wyoming ℞ Date: Sept. 15, 2010 Acetylsalicylic Acid 100 mg Caffeine Citrate 20 mg Lactose q.s. Ft. Caps #20 (Content of each capsule= 150 mg) Sig: Two caps p.r.n. pain. Not to exceed 8 caps/day. Refills: 4 Lab 4: Capsules & Tablet testing (USP) 25 PHCY 6101- Dose Form Lab Fall 2010 Method 1. Weigh all ingredients required to fill 20 caps. 2. Use capsule size #4. 3. Use instructions available near capsule filling machine. 4. The weight of an empty capsule shell is ~35 mg. Use this information as tare for your filled capsules when verifying the uniformity of the encapsulation process (±5% is the acceptable error). Adjust powder as needed. 5. Dispense in container provided. 6. Label as required. Components of hand-operated gelatin capsule filling machine (Feton Fastlock Model 100 machine) There are two main components to the capsule filling machine: 1. The loading device (labeled #1) 2. The capsule filling machine (with the following components making up the machine) a. The upper white sheet (#2) with a transparent cover (#6), lateral handles (#7)and locking mechanisms (#9) b. The powder tray (#3) – this is only in place when filling capsules with powder c. The steel sheet (#4) i. The Fastlock lever (#5) with the lever positioned to the right in the unlocked position and moving the lever to the left middle position locks the capsule bodies into place. ii. The bottom white sheet (#8) used to push capsule parts back together. Lab 4: Capsules & Tablet testing (USP) 26 PHCY 6101- Dose Form Lab Fall 2010 LABORATORY 5 OINTMENTS & MEDICATED STICKS Objectives Appreciate the main functions of topically applied pharmaceuticals: protection, hydration and drug delivery. Practice the preparation of ointments and medicated sticks, using various techniques and types of ointment bases. References: USP 23/NF 18 Remington's , 21st edition, (2006). Pharmaceutical Dosage Forms and Drug Delivery Systems: H. Ansel, N. Popovich and L. Allen, 8th edition (2005). Allen’s compounded formulations: Loyd V. Allen, Jr, APhA, 2003. Ointments are semi-solid preparations containing dissolved or dispersed drugs (medicated) or no drug (nonmedicated) intended for external application to the body. They should be of such composition that they soften, but not necessary melt, when applied to the skin. Nonmedicated ointments are generally referred to as ointment bases and used as such for their emollient or lubricating effect or used as vehicles in the preparation of medicated ointments. Ideally, an ointment base should be compatible with the skin, stable, permanent, smooth and pliable, nonirritating, nonsensitizing, inert and readily able to release its incorporated medication. Both on a large and a small scale, ointments are prepared by two general methods: (1) incorporation and (2) fusion. The method for a particular preparation depends primarily upon the nature of the ingredients. In the incorporation method, the components of the ointment (ointment base, active ingredients, and other excipients) are mixed together by various means until a uniform preparation has been attained. By the fusion method, all or some of the components of an ointment are combined by being melted together and cooled with constant stirring until congealed. Those components not melted are generally added to the congealing mixture, as it is being cooled and stirred. Sticks are a convenient dosage form for administering topical medications; they are not limited to the lips. They can be prepared in several different sizes and Lab 5: Ointments & Sticks 27 PHCY 6101- Dose Form Lab Fall 2010 shapes, for application to different areas of the body. Medicated sticks may be used to administer local anesthetics, antibiotics, antivirals, oncology drugs, and sunscreens. The consistency of sticks comes from a combination of waxes, polymers, resins, oils, gels, dry solids fused into a firm mass, which will soften at body temperature. Laboratory Exercise 1: Hydrocortisone ointment – Incorporation method John Robinson, MD 11123 Freemarket St. Johnston, FA 98765 Tel. (123) 9876-1234 Name: Address: Arthur Beck 7890 Airport Rd. Laramie, Wyoming Date: Sept. 22, 2010 ℞ Hydrocortisone Lactic acid (sp. gr. 1.25) Urea P Water **Hydrophilic petrolatum qs ad 0.3 g 1.5 ml 3g 4.5 ml *30 g Sig. Apply to affected area up to q.i.d. x 1 wk Refills: 2 * For 30 g prescribed prepare 40 g of hydrocortisone ointment. ** Hydrophilic petrolatum required for this formulation must be prepared according to the following recipe: Cholesterol 30 g Stearyl alcohol 30 g White wax 80 g White petrolatum 860 g a) Prepare 40 g in a 100 mL beaker. Calculate the quantity of each ingredient required for the prescription. b) Accurately weigh each ingredient. c) Place the stearyl alcohol, white wax, and white petrolatum in a suitable container and melt the ingredients, using a water bath. d) Add the cholesterol and stir until the mixture is blended completely. e) Remove the mixture from the bath and stir until congealed (~ 15 min). May immerse beaker in a container with cold water to speed up congealing. Method: 1. Weigh accurately all ingredients. 2. Place urea and purified water in a beaker. Stir until dissolution. 3. Measure lactic acid using pipette and add to beaker containing urea solution. Lab 5: Ointments & Sticks 28 PHCY 6101- Dose Form Lab Fall 2010 Mix well. Reserve this mixture. 4. On ointment tile, mix well Hydrocortisone powder with approximately the same amount of hydrophilic petrolatum to form a lump-free paste. 5. Incorporate the rest of hydrophilic petrolatum using geometric dilution. 6. Open a small space on center of hydrophilic petrolatum -drug mix and start incorporation of urea-lactic acid solution into the ointment, very gradually, using two plastic spatulas and being careful not to lose any of the solution. 7. Using spatulation work final ointment until completely smooth. 8. Add all ointment to the bottom of a small zip plastic bag and close it. 9. Cut with scissors one corner of zip bag (very small hole) and squeeze ointment into 1 oz. plastic ointment tube. 10. Tap ointment tube frequently on bench and/or use spatula or short glass rod to remove trapped air which will not allow ointment to go inside. 11. Seal end of tube using tube heat sealer (heat setting at 6; hold arm of sealer [black button] until light goes off then an additional 3 seconds). 12. Label tube. 13. Clean glassware and ointment tile with paper towels before washing. Laboratory Exercise 2: Benzoyl peroxide ointment (for cold sores and lip irritations) – Fusion method Margaret Long, MD 11123 Freemarket St. Johnston, FA 98765 Tel. (123) 9876-1234 Name: Address: Beth Barbour 7890 Airport Rd. Laramie, Wyoming Date: Sept. 22, 2010 *Benzoyl peroxide Polyethylene Glycol 400 (sp. gr.=1.12) Polyethylene Glycol 3350 M. Ft. 1 oz. Sig. Apply to affected area t.i.d. Refills: 1 5% 50% 45% ℞ * Clean balance immediately with wet paper towels if any spills occur. Method: 1. Heat PEG 400 and PEG 3350 to ~ 55°C on top of hot plate to obtain a clear viscous liquid. 2. Remove from heat and add benzoyl peroxide. Mix well using stirring rod until dissolution. 3. Cool slightly and pour into a 1 oz. ointment jar. Product will congeal slowly. 4. Label and dispense. 5. Clean glassware with paper towels before washing. Lab 5: Ointments & Sticks 29 PHCY 6101- Dose Form Lab Laboratory Exercise 3: Fall 2010 Beeswax lip stick with sunscreen (SPF 15) (lip protectant with sunscreen) – Fusion method William D. Thompson, MD 11123 Freemarket St. Johnston, FA 98765 Tel. (123) 9876-1234 Name: Address: Vanessa Williams 7890 Airport Rd. Laramie, Wyoming Date: Sept. 22, 2010 ℞ Octyl methoxycinnamate Oxybenzone White wax (beeswax) Canola oil Petrolatum Flavoring oil q.s. Coloring (oil based) q.s. Sig. Apply to lips prn 0.35 ml 0.15 g 2g 5 ml 0.5 g 1-2 drops (if desired) tip of spatula (if desired) * If this recipe is doubled it will fill one stick container and one ¼ oz. jar. Method: 1. Turn on water bath on high setting until boiling then reduce heat to slow simmer. 2. Accurately weigh all solid ingredients. 3. Use beaker to weigh petrolatum (too small quantity and sticky). Add white wax and canola oil and heat on water bath until mixture becomes a clear pale yellow liquid. Do not boil! 4. Using glass rod to stir continuously, add octyl methoxycinnamate and oxybenzone. 5. Remove preparation from heat and cool until “hazy” before adding flavoring oil and coloring, if desired. 6. Add flavoring (1-2 drops) and coloring (tip of small spatula), if desired. 7. Pour preparation into lip balm stick containers or ¼ oz. jars. 8. Label final product with”Beeswax Lip balm SPF 15” only. Take home (School and University not liable), if desired. 9. Clean all glassware with paper towels before washing. Lab 5: Ointments & Sticks 30 PHCY 6101- Dose Form Lab Fall 2010 LABORATORY 6 CREAMS, LOTIONS & PASTES Objectives Understand the availability of a range of dosage forms used to deliver a drug topically to the skin to treat various disorders. Identify the steps involved in the preparation of semisolid dosage forms intended to be applied externally to the skin or mucous membranes. Practice the preparation of a fluid emulsion (lotion), which has lubricating effect thus being applied to intertriginous areas of the body (areas where the skin rubs together, such as between the fingers, between the thighs, or under the arms). Practice the extemporaneous preparation of a w/o emulsion base (cold cream) from individual ingredients using fusion method. Practice the preparation of a medicated paste by incorporation of the drug (insoluble powder) into a commercially prepared base (white petrolatum). References: USP 23/NF 18 Remington's , 21st edition, (2006). Pharmaceutical Dosage Forms and Drug Delivery Systems: H. Ansel, N. Popovich and L. Allen, 8th edition (2005). Allen’s compounded formulations: Loyd V. Allen, Jr, APhA, 2003. The art, science, and technology of pharmaceutical compounding, Loyd V. Allen, Jr, 2nd edition, APhA, 2002. Creams are emulsified ointments. They are defined as viscous liquid or semisolid emulsion systems either the oil-in-water or the water-in-oil type with a typical "creamy white" appearance. This contrasts them with simple ointments, which are usually translucent. The internal phase of the emulsion reflects light, giving them their characteristic appearance. Creams are usually employed as emollients or as medicated applications to the skin. Creams are generally prepared by fusion method. The aqueous and oil phases are heated separately to somewhere between 60° and 80° C. If an o/w system is to be formed, the emulsifiers are added to the aqueous phase and the emulsion is formed by slow addition of the oil phase with agitation. If a w/o emulsion is to be made, the addition steps are usually reversed. Lotions are usually liquid suspensions or emulsions intended for external application to the skin and mucosa. They are frequently prepared by triturating the Lab 6: Creams, Lotions & Pastes 31 PHCY 6101- Dose Form Lab Fall 2010 ingredients to a smooth paste and then cautiously adding the remaining liquid phase. High speed mixtures or homogenizers produce better dispersions and are, therefore, the tools of choice in the preparation of larger quantities of lotion. Because the dispersed phase of lotions tend to separate from the vehicle upon standing, they should be shaken vigorously before each use to redistribute any separated matter. Pastes are basically ointments into which a higher percentage of insoluble solids have been added, as much as 50% by weight in some instances, intended for external application to the skin. They differ from ointments primarily in that they generally contain a larger percentage of solid material and as a consequence are thicker and stiffer than ointments. Because of the stiffness and absorptive qualities of pastes, they remain in place after application with little tendency to soften and do not flow at body temperature, being therefore effectively employed to absorb serous secretions from the site of application. Pastes are prepared similarly to ointments. However, when a levigating agent is to be used to render the powdered component smooth, a portion of the base is often used rather than a liquid material that would soften the paste. Laboratory Exercise 1: Cold Cream, USP (w/o emulsion base; fusion method) Ronald P. Burton, MD 11123 Freemarket St. Johnston, FA 98765 Tel. (123) 9876-1234 Name: Address: Mary E. Scotch 123 Grand Ave. Laramie, Wyoming ℞ Cetyl Ester Wax (spermaceti) White Wax Mineral Oil (sp.gr. = 0.845) Sodium Borate P. Water q.s. Date: Sept. 29, 2010 125 g 120 g 560 g 5g 1000 g Ft. 30 g Sig: Apply ad. lib. to soothe and soften the skin. Refills: 2 Lab 6: Creams, Lotions & Pastes 32 PHCY 6101- Dose Form Lab Fall 2010 Method: Cold Cream is a traditional w/o emulsion base, available as a commercial base or prepared extemporaneously from individual ingredients. Check traditional references and compounding books for a description of the method to prepare it. Laboratory Exercise 2: Calamine Lotion, USP John. D. Parker, MD 11123 Freemarket St. Johnston, FA 98765 Tel. (123) 9876-1234 Name: Address: Jane Dickens 123 Grand Ave. Laramie, Wyoming Date: Sept. 29, 2010 ℞ Calamine Zinc Oxide Glycerin Microcrystalline cellulose Carboxymethylcellulose (LV) Calcium Hydroxide sol. (lime water) q.s. 4.8 g 4.8 g q.s. for levigating 1.2 g 1.2 g 60 ml Sig. Apply to poison ivy every 4 hours as needed. Refills: 1 * Do not use stir bar during this lab. Method 1. Accurately measure each ingredient. 2. Add calamine, zinc oxide and carboxymethylcellulose to a glass mortar and triturate well with pestle until mixture shows a light homogeneous pink color (no white streaks). Use a plastic spatula to help dislodge material stuck to walls of mortar and pestle as you triturate. 3. Add glycerin to this mixture and mix well. The result will be a lightly wetted, thick, calamine paste. Reserve. 4. Add microcrystalline cellulose to a clean porcelain mortar. Measure 25 mL of calcium hydroxide solution and add to microcrystalline cellulose. Mix well. 5. Add small portions of this mixture gradually, and with vigorous mixing (using pestle), to the glass mortar containing calamine paste. The resultant preparation (primary suspension) should be thoroughly mixed until lump-free. 6. Measure an additional 15 mL of calcium hydroxide solution and use it to dilute the preparation to a pourable liquid. 7. Pour into a 100-mL cylinder. 8. Rinse mortar with additional calcium hydroxide solution to make final volume to 60 mL, by mixing well to “rinse” mortar and pestle. Add this “rinse” to cylinder. Lab 6: Creams, Lotions & Pastes 33 PHCY 6101- Dose Form Lab Fall 2010 9. Transfer contents in cylinder to a 2 fl. oz. lotion bottle. Shake vigorously to homogenize final lotion. 10. Wash all glassware after use. Clean sink with wet paper towels to remove pink residue. Laboratory Exercise 3: Zinc Oxide Paste (astringent and protectant; used for diaper rash and bed sores; incorporation method) Henry A. Hampton, MD 11123 Freemarket St. Johnston, FA 98765 Tel. (123) 9876-1234 Name: Age: Address: Beth A. Stuart 5 months old 1928 N. 15th Street Laramie, Wyoming Date: Sept. 29, 2010 ℞ Zinc Oxide 25% Starch 25% White Petrolatum q.s. 1000 g Ft. 30 g Sig: Apply to affected area after each diaper change. Do not rub into the skin. Refills: 4 Method: Zinc oxide paste is a traditional paste prepared extemporaneously from individual ingredients. Check traditional references and compounding books for a description of the method to prepare it. Lab 6: Creams, Lotions & Pastes 34 PHCY 6101- Dose Form Lab Fall 2010 LABORATORY 7 GELS & GUMMY LOZENGES Objectives Appreciate the importance of gels as drug delivery systems for various routes of administration and compatible with many different drug substances. Practice the preparation of two gels for topical application using different types of gelling agents: carbomer resin, which will wet rapidly and a cellulose derivative which hydrates slowly. Practice the preparation of solid dosage forms for slow dissolution in the mouth for local effect in the oral cavity (mouth and throat). Understand the potential danger of gummy lozenges to children since these dosage forms may look and taste like candy. References: USP 23/NF 18 Remington’s, 21st edition, (2006). Pharmaceutical Dosage Forms and Drug Delivery Systems: H. Ansel, N. Popovich and L. Allen, 8th edition (2005). Allen’s compounded formulations: Loyd V. Allen, Jr, APhA, 2003. Gels or Jellies are semisolid systems consisting of suspensions made up of either small inorganic particles or large organic molecules interpenetrated by a liquid (USP23/NF18). Gels are semirigid systems in which the movement of the dispensing medium is restricted by an interlacing three dimensional network of particles or solvated macromolecules of the dispersed phase. Most gels act as absorption bases and are water washable, water soluble, water absorbing, and greaseless. Gels can be used to administer medications orally, topically, intranasally, vaginally, and rectally. Gels generally should be stored in tight containers and are commonly dispensed in tubes, jars, squeeze bottles, or pump dispensers. Beyond-use dates for water-containing formulations are no later than 14 days for products prepared from ingredients in solid form. In preparing a gel the active drug may be added before or after the gel is formed. If the active drug does not interfere with the gelling process, it is best to add it prior to gelling because the drug will be more easily and uniformly dispersed. Hydroxypropyl cellulose powder can be dispersed slowly under stirring in diluted isopropyl alcohol forming a clear gel with partially hydrated particles that will swell to sticky gel grains visible at naked eye. Final hydration and thickening happens Lab 7: Gels and Gummy Lozenges 35 PHCY 6101- Dose Form Lab Fall 2010 slowly after the final product is allowed to stand for about 1 hr with occasional gentle stirring. Carbomer resins are primarily used in aqueous systems, although other liquids may be used as well. In water, a single particle of carbomer will wet rapidly, but like many other powders, carbomer polymers tend to form clumps of particles when dispersed haphazardly in polar solvents. To achieve the fastest dispersion of a carbomer resin, one should take advantage of the very small particle size of the carbomer powder and add it very slowly into the vortex of the liquid which is being stirred rapidly. Almost any device like a simple sieve that can sprinkle the powder on the rapidly stirred liquid is useful. High shear mixers should not be used as they can break down the polymers and reduce gel viscosity. Once the powder is incorporated, continued stirring for 10-15 minutes at reduced speed is recommended to avoid excess air entrapment. A neutralizer will thicken the gel if desired; triethanolamine will neutralize carbomer resins containing up to 50% ethanol. Lozenges or Troches are solid oral preparations, which are intended to dissolve or disintegrate slowly in the mouth. They contain one or more medications, usually in a flavored, sweetened base. They can be prepared by several different methods, resulting into hard lozenges (hard candy-like), soft lozenges (chocolate, polyethylene glycol, or sugar-acacia) or chewable gummy gel lozenges (glycerinated gelatin). Lozenges have traditionally been used for local irritation or infections of the mouth or throat (topical anesthetics, antibacterial agents). More recently, lozenges are being used as a way to deliver drugs systemically. As the lozenge dissolves slowly in the mouth, the drug is released for absorption in the mouth, either buccally or sublingually, and the drug that is swallowed can be absorbed in the gastrointestinal tract. Lozenges are especially useful for patients who have difficulty swallowing oral solid medications such as pediatric and geriatric patients. To enhance patient compliance, especially in children, lozenges are formulated to taste good. Because they may look and taste like candy, lozenges are a potential danger to children; households with children should be warned to keep these products out of reach of children. Lab 7: Gels and Gummy Lozenges 36 PHCY 6101- Dose Form Lab Laboratory Exercise 1: Fall 2010 Piroxicam Alcoholic Gel (topical non-steroidal anti-inflammatory gel) Erasmus B. Dragon, MD 100 S. Main Street, suite 40 Laramie, WY 82070 Tel. (307) 742-1234 Rx Sarah Plumb Date: Oct. 6, 2010 * Piroxicam 500 mg Hydroxypropylcellulose (HPC) 1.75 g Propylene Glycol 4 mL Polysorbate 80 2 mL 70% Isopropyl Alcohol q. s. 100 mL (=97 mL) Ft. 1 fl. oz.** Sig. Apply to affected area bid Refill – NR 1 2 3 4 prn Erasmus B. Dragon M.D. Piroxicam 20 mg capsules are available to compound this formulation. Prepare 35 mL of Rx. The final gel product will have a yellow, opaque color (not “clear”). * ** Method: 1. Pre-calibrate the final container for 1 fl.oz. Reserve. 2. To a beaker containing 25 mL of 70% isopropyl alcohol sprinkle slowly HPC powder under continuous, slow stirring (use glass rod). Mix until a clear liquid gel results (visible jelly droplets, not to confound with air bubbles). Reserve. 3. Place required amount of piroxicam powder that will give correct amount of drug (weighed out of capsules) in a glass mortar and use pestle to levigate the powder with propylene glycol. 4. Add polysorbate 80 and triturate well. 5. Using geometric dilution, add the hydroxypropylcellulose gel with gentle mixing. The final product will not be a clear gel since piroxicam is sparingly soluble in water and only slightly soluble in alcohol and alkaline aqueous solution. 6. Transfer final gel to a 1 oz. ointment jar and label. There is no valid scientific information to support the stability of this product beyond 14 days. 7. Final hydration and thickening will happen slowly after the final product is allowed to stand for about ~1 hr with occasional, gentle inversion of the container. Do not shake the container with final product as shaking will disrupt complete gel formation. Lab 7: Gels and Gummy Lozenges 37 PHCY 6101- Dose Form Lab Fall 2010 Laboratory Exercise 2: Benzocaine Topical Gel (local anesthetic) Martin House, MD 100 S. Main Street, suite 50 Laramie, WY 82070 Tel. (307) 742-1234 Rx Tracy Lewis Date: Oct. 6, 2010 Benzocaine 2g Carbomer 934 2g Ethanol 95% 90 mL P. Water q.s 100 mL Ft. 30 mL Sig. Apply to affected area 2x day for 2 wks Refill – NR 1 2 3 4 prn Martin House, MD General instructions: Pre-calibrate a beaker for 35 mL and the final container (provided) for 30 mL. Stir bar may be used only on step 3 of method. All other steps that ask for stirring should be done with glass rod. Discard leftover gel into trash can with the help of paper towels before using warm water and detergent to wash glassware. Do not wet/wash the sieve used to add carbomer 934. Return it to original container where you found it. Method: 1. Calculate the required quantity of each ingredient to prepare 35 mL. Accurately weigh/measure each ingredient. 2. Benzocaine is soluble in ethanol and does not disturb gelling process. 3. Carbomer 934 is soluble in alcohol and must be sprinkled very slowly through a sieve on the vortex of the stirred liquid. Additional stirring for ~5 minutes at reduced speed to avoid excess air entrapment is recommended. 4. Final product must be a clear gel. 5. Triethanolamnine (a neutralizer agent), 1-2 gtt, may be added with continuous and quick mixing, if a thicker gel is desired. 6. A light-resistant container with tight closure is recommended. 7. Product must be stored in a cool place and stability studies have shown that a beyond-use date of 30 days can be used. Lab 7: Gels and Gummy Lozenges 38 PHCY 6101- Dose Form Lab Fall 2010 Laboratory Exercise 3: Gummy Gel Lozenges (for sore throat) Erasmus B. Dragon, MD 100 S. Main Street, suite 40 Laramie, WY 82070 Tel. (307) 742-1234 Rx Sarah Plumb Benzocaine Diphenhydramine hydrochloride Gelatin Glycerin (sp. gr.=1.258) P water Bentonite Aspartame Acacia powder(gum arabica) Citric acid (monohydrate) Flavoring (optional) Coloring (optional) Date: Oct. 6, 2010 0.01 gram 0.06 gram 7.6 gram (1 packet) 27 ml 3.8 ml 0.1 gram 0.1 gram 0.1 gram 0.11 gram 5-10 drops 1-2 drops Sig. One lozenge p.o. q 4-6 hr prn soothing irritated throat Refill – NR 1 2 3 4 prn Erasmus B. Dragon M.D. General instructions: 1. Obtain the following: • large piece of butcher paper and tape it to your workbench (less bench cleanup). • small piece of wax paper (to mix medicated powder mixture). • one packet of gelatin (to prepare gummy gel base). • 6 medicine cups (molds for lozenges), mark fill level on the outside surface, spray with cooking spray and spread/remove excess with Q-tips. • Small zip bag to store final lozenges (protection from drying out and hardening). 2. Weigh glycerin in porcelain casserole. 3. Do not use stir bar for this preparation. Method: 1. Start water bath at medium setting. 2. On top of a piece of wax paper, blend well by spatulation: benzocaine + diphenhydramine hydrochloride + bentonite + aspartame + acacia powder + citric acid monohydrate. Reserve this dry powder mixture next to water bath. 3. Heat casserole containing glycerin on boiling water bath (change setting to HIGH until water is bubbling then turn it down to soft boiling) until it becomes less viscous, and then add purified water (3.8 mL). Stir to mix. Lab 7: Gels and Gummy Lozenges 39 PHCY 6101- Dose Form Lab Fall 2010 4. Heat until mixture is very fluid and warm, stirring occasionally with glass stirring rod. 5. With casserole inside water bath (careful to not get water inside the prep) sprinkle gelatin very slowly by portions with thorough and continuous mixing (use glass rod to dissolve clumps) after each addition. Mix well until the product is lump-free and clear. Do not boil this mixture! 6. Turn off hot plate. Remove casserole from heat and immediately incorporate dry powder mixture prepared in step 1. Stir until evenly dispersed. 7. Let product cool for ~1 min. While the product is warm (not very hot) add the flavor concentrate and coloring (if desired) and mix well. 8. Pour immediately into oiled molds. 9. Lozenges are placed in the refrigerator for approx. 15-30 min.to speed solidification. Remove lozenges from molds with help of a fine spatula. 10. If mixture is too thick to pour into molds, place casserole back for a few minutes inside the hot water bath. Do not turn heat on. 11. Roll lozenges on sugar (if desired). Wrap each individual dosage unit with plastic wrap and store into zip bag. Label. Lab 7: Gels and Gummy Lozenges 40 PHCY 6101- Dose Form Lab Fall 2010 LABORATORY 8 SUPPOSITORIES Objectives Appreciate the importance of suppositories as dosage forms that allow administration of drugs (locally or systemically) through the rectum, vagina or urethra, to severely debilitated patients, to infants and small children, to those who cannot swallow, and those whom the parenteral route is unsuitable, Practice the preparation of suppositories for children and adults. Practice the preparation of rectal and vaginal suppositories. Practice the preparation of suppositories using different types of suppository bases (oil-soluble and water-soluble). References: USP 23/NF 18 Remington's , 21st edition, (2006). Pharmaceutical Dosage Forms and Drug Delivery Systems: H. Ansel, N. Popovich and L. Allen, 8th edition (2005). Allen’s compounded formulations: Loyd V. Allen, Jr, APhA, 2003. The art, science, and technology of pharmaceutical compounding, Loyd V. Allen, Jr, 2nd edition, APhA, 2002. Suppositories are solid dosage forms intended for insertion into body orifices where they melt, soften, or dissolve and exert localized or systemic effects. They are commonly employed rectally, vaginally, and occasionally urethrally. Suppository bases play an important role in the release of the medication they hold and therefore in the availability of the drug for absorption. For most purposes, it is convenient to classify suppository bases according to their physical characteristics into the following three categories: fatty or oleaginous bases, water or water-miscible bases, and miscellaneous bases, generally combination of lipophilic and hydrophilic substances. Bases of the first category, include cocoa butter, hydrogenated fatty acids of vegetable oils such as kernel oil, and fatty acid glyceride such as glyceryl monopalmitate. These bases melt at the body temperature to release the medicament. The second category bases are glycerinated gelatin and bases of polyethylene glycols. They dissolve in the body cavity to release the medicament. In the miscellaneous group of bases are mixtures of the oleaginous and water-soluble or water-miscible materials. Most of the time Lab 8: Suppositories 41 PHCY 6101- Dose Form Lab Fall 2010 these mixtures are preformed emulsion of w/o type with the help of surfactants. Suppositories are prepared by two methods: molding from a melt and cold compression. The steps in molding include the melting of the base, incorporation of medication, pouring the melt into molds, cooling and congealing into suppositories and removing the formed suppositories from the mold. In preparation by compression method, the base and the other formulative ingredients are combined by thorough mixing, the friction of the process causing the base to soften into a paste-like consistency. This soften mass is then forced into special molds using suppository making machines. Suppositories must be protected from heat and can be stored in a refrigerator. They should not be frozen. Glycerin and PEG-based suppositories should be protected from moisture, as they are usually hygroscopic. For wrapped suppositories, it is suitable the instruction “Unwrap and insert (rectally or vaginally)” to be included on the labeling. Compounded suppositories are usually considered dry or nonaqueous thus being considered as stable dosage forms as long as protected from moisture and heat. They should have a beyond-use date of 25% of the time remaining on the expiration date if a manufactured product was used, or 6 months, whichever is earlier (USP Chapter <795>). If the product is prepared from USP/NF ingredients, a beyond-use date of 6 months is appropriate unless evidence is available to support other dating. Lab general instructions: Large suppository molds: blank supp =2.2 g Small suppository molds: blank supp = 0.75 g Supp melts (both Rx) should be filled only when the melt is not very hot (temp. of bottom of container does not burn one’s hand). After pouring the melt into supp. molds allow supp.to rest at RT for ~ 5 min. then place them in the refrigerator for ~10-15 min.to hasten solidification. Two sealing machines are available to seal solid suppositories (1.5 setting on sealing machine). Make sure you do not stand in line with suppositories in hand waiting for the sealing machine as the suppositories will melt (final solidification happens only after > 2hr). Lab 8: Suppositories 42 PHCY 6101- Dose Form Lab Fall 2010 Laboratory Exercise 1: Vaginal Progesterone suppositories Raymond V. Holland, MD 11123 Freemarket St. Johnston, FA 98765 Tel. (123) 9876-1234 Name: Address: ℞ Carol P. Hughs 123 Grand Ave. Laramie, Wyoming Progesterone PEG 8000 PEG 400 (sp.gr. 1.12) M. ft. supp. d.t.d. no. 6 Sig: Insert i supp ut dict for PMS Refill: φ Date: Oct. 13, 2010 100 mg 20 parts 80 parts Raymond V. Holland, MD Method: 1. Determine the weight of a blank suppository with PEG base only. Calculate the amounts of ingredients required to prepare the prescription considering two extra supp. to account for losses during melting and pouring 2. Melt both PEGs in a porcelain casserole in the water bath. Stir intermittently. 3. Add powdered progesterone and stir continuously to make suspension. 4. Cool the mixture to just below the melting point before pouring into disposable suppository molds (well secured). Too hot melt may melt/deform the molds. 5. Pour continuously and add a slight overfill (above line marking) to account for shrinkage. 6. Allow melt to congeal for 5 min. at RT then place the mold in the refrigerator for approximately 15 minutes to accelerate solidification. 7. Remove suppository mold from the refrigerator (only when ready to seal) and seal suppository ends using a heat sealer (setting 1.5). 8. Separate individual suppositories and store in an appropriate container. 9. Label and dispense. Lab 8: Suppositories 43 PHCY 6101- Dose Form Lab Fall 2010 Laboratory Exercise 2: Rectal Acetaminophen suppositories (children size) Jean Mitchell, MD 11123 Freemarket St. Johnston, FA 98765 Tel. (123) 9876-1234 Name: James C. Black Age: 4 years old Weight: 33 Lb Address: 987 S. Garfield Laramie, Wyoming ℞ Date: Oct. 13, 2010 Acetaminophen 160 mg Cocoa Butter q. s. M. ft. supp. d.t.d. no. vi Sig: As directed for pain & fever Jean Mitchell, MD Refill: 1 Method: 1. Determine the weight of a blank suppository. Calculate the amounts of ingredients required to prepare the prescription considering two extra supp. to account for losses during melting and pouring. 2. Place cocoa butter in a porcelain casserole and using a metal spatula crush cocoa butter chunks into small pieces, if needed. 3. Placed casserole inside or on top of a water bath (just to get the heat from the steam) and heat cocoa butter until a clear liquid forms, using constant stirring to minimize localized heating (Cocoa butter should not be heated more than 50° C as the final suppositories will not solidify properly). 4. Still under heat, add powdered acetaminophen to melted cocoa butter and stir continuously to make a dispersion. 5. Remove from heat, swirl beaker contents to cool mixture slightly and pour the warm mixture continuously (to avoid layering) into disposable suppository molds placed on a rack (molds need to be well secured during pouring). Slightly overfill the molds (above line marking) to reduce the effect of shrinkage after cooling. 6. Let suppositories congeal at room temperature for ~ 5 min. and then place them in the refrigerator for approximately 15 minutes to speed hardening. 7. Remove suppositories from the refrigerator and seal supp. ends using a heat sealer. 8. Separate each individual suppository and organize them in dispensing container. 9. Label container and dispense. Lab 8: Suppositories 44 PHCY 6101- Dose Form Lab Fall 2010 LABORATORY 9 SOLUTIONS Objectives Understand the basic principles related to the preparation of pharmaceutical solutions. Prepare a topical solution and two oral solutions. In pharmaceutical terms, solutions are defined as liquid preparations that contain one or more soluble chemical substances usually dissolved in water or water miscible pharmaceutical solvents and that do not, by reasons of their ingredients, method of preparation or use, fall into other groups of products. Depending on the intended route of administration, solutions may be classified as: oral (solutions, syrups, elixirs, and spirits), topical (solution, lotion), otic (for the ear), nasal (for the nose), ophthalmic (for the eye), irrigating (to soak or flush wounds and body cavities), parenteral (injections). Aqueous pharmaceutical solutions containing sugar are classified as syrups and sweetened hydroalcoholic solutions are termed elixirs. Oral solutions, syrups, and elixirs are prepared and utilized for the specific effects of the medicinal agents present. In these preparations the medicinal agents are intended to provide systemic effects. These formulations may contain solutes other than the medicinal agent. These additional agents usually are included to provide color, flavor, sweetness, solubilization, or stability to the solution. Pharmacists should be aware of the solubility characteristics of the medicinal agent and solutes in the common pharmaceutical solvents to prepare a stable solution. Solutions intended for topical administration to the skin or mucous membranes are called topical solutions. They are usually aqueous but may also contain other solvents, such as alcohols and/or polyols and several other additives. Aluminum chloride solution in 93% ethanol is used as an astringent in the management of hyperhydrosis (excessive sweating). Unless otherwise designated, the concentration of a typical pharmaceutical solution is expressed as w/v; the solid ingredients are measured by weight and the liquid ingredients by volume. Pharmaceutical solutions, like most solutions, should be absolutely clear and with no evidence of precipitation or decomposition. Solutions may be of different types. Simple solutions are those solutions composed of one substance, which has been dissolved in a liquid. Compound solutions are those containing more than one solute. Chemical solutions are those Lab 9: Solutions 45 PHCY 6101- Dose Form Lab Fall 2010 solutions whose components are the product of a chemical reaction. Saturated solutions are those which contain all the solute that the solvent will hold at a given temperature without precipitation of the solute. Based on the final use, solution may be classified as douches, enemas, gargles, mouthwashes, juices, nasal solutions, and otic solutions. The solvents, which composed the major portion of a solution, should have characteristics to be suitable to use in pharmaceutical solution. In addition to the factor of solubility, the selection is based on such additional characteristics as clarity, low toxicity, and viscosity, compatibility with other ingredients, chemical inertness, palatability, odor, color, and economy. The most common solvent, which meets the majority of the above criteria, is purified water. In many instances when water is used as the primary solvent, an auxiliary solvent is also employed to augment the solvent action of water or to counter any of its deficiency. Alcohol, glycerin, propylene glycol, and polyethylene glycol, perhaps the most used auxiliary solvents. Although in most pharmaceutical solutions, the amounts of solute to be dissolved are usually well below the solubility capacity of the volume of the solvent employed, there are many facets to be considered when preparing solutions. The pharmacist is concerned with not only the individual physical and chemical characteristics of the ingredients and the solvents, but also the correct techniques to be used in handling special problems, which may occur. When readily soluble substances are prescribed with more than enough liquid to dissolve them, the best procedure is to measure about three-fourths of the required quantity of liquid in a graduate, add the substance to be dissolved and stir until solution is effected, make up to the required volume, and filter, when necessary, into another graduate. If the solute dissolves slowly, the solute may be crashed into fine powder and solvent may be heated to enhance solubility process. When two or more solvents are prescribed with several solutes, each solute should be dissolved in the solvent in which it is most soluble before mixing with the other liquids. Drugs administered as aqueous liquids are generally absorbed much more rapidly than those administered in solid form, because the processes of disintegration and dissolution are not required. Pharmaceutical solutions may differ in the type of solvent employed and therefore in their fluidity characteristics, indications and route of administration (oral, rectal, topical, etc). Some solutions, which officially are preparations in which the drug substance is dissolved predominantly in an aqueous vehicle, fall into other categories of pharmaceutical preparations for reasons of their method of preparation (e.g., injections, which must be sterilized). Lab 9: Solutions 46 PHCY 6101- Dose Form Lab Fall 2010 Laboratory Exercise 1: Mouthwash/Gargle (local antiseptic) Name: Johanna Tooke ℞ Date: Oct. 20, 2010 Cetylpyridinium chloride 100 mg Polysorbate 20 1 mL Flavoring oil 0.25 mL Ethanol 95% 10 mL Sodium saccharin 100 mg Sodium benzoate 200 mg Sorbitol 70% sol. 10 mL Coloring (optional) q.s. Purified water q.s. 100 mL Ft. 4 fl.oz. Sig: Use one capful to rinse the mouth and throat q am and hs Refill: NR 1 2 3 4 prn Leonard Palmer, M.D. Method: 1. Calibrate to 120 mL a 4 oz. Rx bottle. 2. Calculate the quantity of each ingredient required for the prescription. 3. Accurately weigh or measure each ingredient. 4. Add flavoring oil to polysorbate 20 and mix well. 5. Add the ethanol and mix well. 6. Separately, add the cetylpyridinium chloride, sodium saccharin, and sodium benzoate to about 80 mL of purified water, followed by the sorbitol solution. 7. Combine the two solutions together, by portions, under continuous mixing. 8. Add a few drops of food coloring, if desired. 9. Add sufficient pH2O to volume and mix well. 10. Package and label. Laboratory Exercise 2: Phenobarbital 0.4% Oral Solution Name: Mark Mitchell ℞ Phenobarbital Tween 80 Sodium Saccharine Lemon Oil Citric Acid Glycerin Methylparaben P. Water q.s. Ft. 2 fl. oz. Sig: One tsp at h.s. Refill: φ Date: Oct. 20, 2010 0.20 g 4.00 mL 0.10 g 0.25 mL 0.20 g 4.00 mL 0.10 g 50.0 mL Jean Coats, M.D. Lab 9: Solutions 47 PHCY 6101- Dose Form Lab Fall 2010 Method: 1. Using hot plate heat 30 ml of p. water to 60° C. 2. Add Tween 80 to the water with slow stirring (stir bar) to prevent formation of foam. 3. Turn off heat. 4. Under continuous stirring, add phenobarbital powder by portions until dissolution. 5. Add separately, with continuous stirring, sodium saccharine, citric acid and methylparaben. 6. Still under stirring, add glycerin and mix well. 7. Cool product to room temperature and add lemon oil. Mix well. 8. Add a few drops of food coloring, if desired. 9. Final product may be initially turbid but will clear later. 10. Make up the volume with p. water. Transfer product to a 2 oz. prescription bottle. Laboratory Exercise 3: Metoprolol Tartrate 10 mg/mL Oral Liquid Name: Robert D. Scarlet ℞ Metoprolol Tartrate Vehicle Ft. 2 fl. oz Sig: i tsp am & hs Refill: 5 Date: Oct. 20, 2010 q.s. 1.0% 120 mL Aaron Johnson, M.D. *Metoprolol 100 mg tabs are available as source of the drug and Syrup, NF is available as vehicle. Coloring and flavoring may be added for taste appeal. Method: 1. Using a glass mortar and pestle, pulverize the required number of metoprolol tartrate tablets to a fine powder. 2. Levigate with glycerin (~until a uniform paste is formed. 3. Add 15 ml of vehicle and triturate until uniform. 4. Under continuous trituration add vehicle in approximately geometric portions almost to volume, mixing thoroughly after each addition. 5. Add a few drops of flavoring and food coloring, if desired. 6. Transfer to a graduate cylinder and complete to volume 7. Transfer the preparation to a prescription bottle. * Alternative vehicles for the compounding pharmacist in which the stability of this product has been determined include: • Equal mixtures of Ora Sweet™ + Ora Plus • Equal mixtures of Ora Sweet SF+ Ora Plus SF Lab 9: Solutions 48 PHCY 6101- Dose Form Lab Fall 2010 LABORATORY 10 SYRUPS Objectives Practice the preparation of medicated syrups. Be aware of the main components of syrups, including sucrose and non-sucrose based syrups. Learn the importance of flavorings, colorants and antimicrobial preservatives in the preparation of aqueous, sweetened solutions. References: Remington's , 21st edition, (2006). Pharmaceutical Dosage Forms and Drug Delivery Systems: H. Ansel, N. Popovich and L. Allen, 8th edition (2005). Aqueous pharmaceutical solutions containing sugar or sugar substitutes are classified as syrups. In these preparations, the medicinal agents are intended to provide systemic effects. These formulations may contain solutes other than the medicinal agent. These additional agents usually are included to provide color, flavor, sweetness, solubilization, or stability to the solution. Pharmacists should be aware of the solubility characteristics of the medicinal agent and solutes in the common pharmaceutical solvents to prepare a stable solution. Most pharmaceutical syrups contain the following components in addition to purified water and any medicinal agents present: (1) the sugar, usually sucrose, or sugar-substitutes used to provide sweetness and viscosity, (2) antimicrobial preservatives, (3) flavorants, and (4) colorants. Also, many syrups, especially those prepared commercially, contain special solvents, solubilizing agents, thickeners, and stabilizers. Simple syrup (or Syrup, NF) contains 85% w/v sucrose and is prepared by heating a mixture of sucrose and purified water. It requires no additional preservation if it is to be used soon; in the official syrup, preservatives are added if the syrup is to be stored. Lab 10: Syrups 49 PHCY 6101- Dose Form Lab Fall 2010 Laboratory Exercise 1: Promethazine Syrup (compare to Phenergan Syrup™) Michael D. Fox, MD 100 S. Main Street, suite 50 Laramie, WY 82070 Tel. (307) 742-1234 Rx Mark C. Mitchell Date: Oct. 27, 2010 *Promethazine HCl 1. 25 g Cocoa 180 g Sucrose 500 g Glycerin 50 mL Sodium Chloride 2.0 g Vanillin 0.2 g Sodium Benzoate 1.0 g P. Water q.s. 1000 mL **Ft. 60 mL Sig: Dosage regimen used for allergy (search for accurate instructions for the product label) Refill: 3 Michael D. Fox, MD Promethazine 25 mg tabs are available as source of the drug in this formulation. Each tablet weighs 0.2 g in average. ** Prepare 70 mL of Rx. * Method: 1. Mix sucrose and cocoa in a large beaker. 2. To this mixture gradually add glycerin and vanillin. Reserve this cocoa mixture. 3. In a small beaker containing a small amount (15 mL) of hot water dissolve sodium benzoate and sodium chloride. 4. Crush promethazine tabs with mortar and pestle then add it to the mixture prepared in step 3. Mix well. 5. Combine promethazine solution and cocoa mixture. Add some water to make it a pourable liquid. 6. Bring the entire mixture to boiling temperature for 2 min (Do not overboil as it will start burning!). 7. Remove from heat source and stir the preparation to allow cooling to room temperature. 8. Add sufficient p. water to make up the final volume. Transfer to a prescription bottle, label and dispense. Lab 10: Syrups 50 PHCY 6101- Dose Form Lab Laboratory Exercise 2: Fall 2010 Acetaminophen Syrup (similar to Children’s Tylenol® suspension, liquid, or elixir) Michael D. Fox, MD 100 S. Main Street, suite 50 Laramie, WY 82070 Tel. (307) 742-1234 Rx Name: Michelle Stein Age: 2 yo Date: Oct. 27, 2010 ℞ Acetaminophen (active ingred.; analgesic, antipyretic) Benzoic acid (antimicrobial preservative) Disodium calcium EDTA (chelating agent; stabilizer) Propylene glycol (thickening agent; co-solvent; sweetener) Alcohol (co-solvent; antimicrobial) Saccharin sodium (artificial sweetener) P. water (solvent) Flavor (optional) Color (optional) Sorbitol solution (non-sugar syrup vehicle) q.s. Ft. 60 mL Sig: Usual dosage regimen for this age Refill: 2 24 g 1.0 g 1.0 g 150 mL 150 mL 1.8 g 200 mL q.s q.s 1000 mL Michael D. Fox, MD Method: Find the best method to prepare this prescription. Research the directions required for the Signa considering this patient’s age and using the USP DI, PDR or any other available reference. Prepare appropriate labeling. Submit method for BONUS grade. Guidelines for preparation: Check each solute’s solubility using the Merck Index, Remington’s and other suitable references available in Lab bookshelves. Syrups are frequently prepared by simple methods commonly used to prepare solutions. Most solutions are prepared by simple mixture of the solutes with the solvent. Depending on the physical and chemical characteristics of the ingredients, some solutes may require an extended time for dissolving in a given solvent. As a result, some techniques may be employed to hasten dissolution: 1. Solution of the ingredients with the aid of heat 2. Reduction of the particle size 3. Use of a solubilizing agent or co-solvent 4. Solution of the ingredients by vigorous agitation 5. A mixture of the above techniques. Lab 10: Syrups 51 PHCY 6101- Dose Form Lab Fall 2010 Some basic compounding principles include: • Checking solubility of chemical(s) in solvent(s)/vehicle(s) • Viscous solvent/vehicle(s) should be added at the end, unless used as a solubilizer or levigating agent • Time to dissolve may be decreased by reduction of particle size and/or use of heat (check heat-stability of chemicals) • Chemical(s) must stay in solution: check solution saturation concentration • Stability of chemical(s) in solution: addition of stabilizers • Masking of flavor/odor should be considered to increase patient compliance: matching of flavoring with coloring. • Addition of antimicrobial preservative(s) will maintain the preparation free of microbial growth while in use. Lab 10: Syrups 52 PHCY 6101- Dose Form Lab Fall 2010 LABORATORY 11 ELIXIRS & TINCTURES Objectives Recognize the main ingredients of an elixir and a tincture. Practice the preparation of elixirs and tincture. References: Remington's , 21st edition, (2006). Pharmaceutical Dosage Forms and Drug Delivery Systems: H. Ansel, N. Popovich and L. Allen, 8th edition (2005). Elixirs are clear, sweetened hydroalcoholic solutions intended for oral use and are usually flavored to enhance their palatability. The proportion of alcohol present in elixirs varies widely since the individual components of the elixirs have different water and alcohol solubility characteristics. Although many elixirs are sweetened with sucrose or with a sucrose-syrup, some utilize sorbitol, glycerin and/or artificial sweeteners. Elixirs containing more10 to 12% of alcohol are usually self-preserved and do not require additional antimicrobial agent for their preservation. Elixirs are prepared by simple solution with agitation and/or by admixture of two or more liquid ingredients. Alcohol-soluble and water-soluble ingredients are usually dissolved separately in alcohol and purified water, respectively, and then the aqueous solution is added to the alcoholic solution with continuous agitation to prevent separation of the alcohol-soluble components. Ingredients that will increase the viscosity of the elixir will contribute to the solvent effect of the hydroalcoholic vehicle, assist in the dissolution of the solvent, and enhance the stability of the preparation. However, these agents will slow the rate of filtration (with the aid of talc) if flavoring oils separate due to the reduced alcoholic concentration (cloudy elixir). Tinctures are alcoholic or hydroalcoholic solutions prepared from vegetable materials or from chemical substances. They may be prepared by various methods and may vary in strength of the active ingredient, alcoholic content, and intended use. Depending on the preparation, tinctures may contain alcohol in amounts ranging from 15-80%. Very few tinctures are used for oral administration at present. Usually, patients requiring oral medications prefer to take a tablet or capsule or a pleasant-tasting elixir or syrup. Paregoric, USP is the typical example of a medicated tincture taken orally and Iodine tincture is the representative of a tincture for topical Lab 11: Elixirs & Tinctures 53 PHCY 6101- Dose Form Lab Fall 2010 application still used nowadays. Because of the usual content of volatile oils and alcohol, elixirs and tinctures should be stored in tight, light-resistant containers and protected from heat and sunlight. Laboratory Exercise 1: Terpin Hydrate and Dextromethorphan Elixir (expectorant & antitussive) Name: James Gibson Date: Nov. 3, 2010 ℞ Terpin Hydrate Dextromethorphan HBr Orange Oil Benzaldehyde Sorbitol Solution Propylene Glycol Alcohol P. Water q.s. Sig: ii tsp q 6 hrs prn cough. Refill: 2 2.0 g 0.2 g 0.8 mL 0.2 mL 10 mL 40 mL 40 mL 100 mL Ken Kelvin, M.D. Method 1. 2. 3. 4. Dissolve terpin hydrate in 40 ml of alcohol. Add propylene glycol and mix well. Reserve. Dissolve dextromethorphan in 5 ml water. Add slowly with constant stirring aqueous dextromethorphan solution to alcoholic terpin solution. 5. With continuous stirring add slowly orange oil and benzaldehyde. 6. Add sorbitol solution. Mix well. 7. Transfer the solution to a graduate cylinder or a premarked prescription bottle. Add sufficient water to make up the volume to 100 mL, mixing the liquid as water is added. 8. If the product is cloudy, filtration may be required. 9. Label product. 10. Auxiliary labels: May cause drowsiness; Do not drink alcoholic beverages Lab 11: Elixirs & Tinctures 54 PHCY 6101- Dose Form Lab Laboratory Exercise 2: Fall 2010 Hyoscyamine Elixir (compare to Levsin® elixir = 0.125 mg hyosciamine sulfate per 5 mL; 20% alcohol) Name: Bernice Meza Age: 52 yo Diagnosis: Peptic ulcer ℞ Date: Nov. 3, 2010 25 mg Hyoscyamine SO4 (active ingredient; drug) Orange oil (flavoring) 10 mL Lemon oil (flavoring) 4 mL Coriander oil (flavoring) 1.6 mL Anise oil (flavoring) 2.4 mL Tween 20 (surfactant, levigating agent) 40 mL Alcohol (solvent; antimicrobial preservative) 200 mL Sorbitol solution (aqueous sweetened vehicle/solvent) 400 mL Coloring q.s. P. Water (vehicle/solvent) q.s. 1000mL Ft. 60 mL Sig: ____________________________________ Refill: 0 Kathryn Martin, M.D. Method: • Propose a good method to prepare this elixir, using knowledge and skills already acquired. Read “preparation of elixirs” in Dose Form textbook. Laboratory Exercise 3: Iodine Tincture (local anti-infective agent) Name: Your name Address: Laramie, Wyoming ℞ Iodine Sodium Iodide Alcohol P. Water q.s. Date: Nov. 3, 2010 0.60 g 0.74 g 15.0 mL 30.0 mL Sig: Apply over the affected skin area 2-3 x day Refill: 0 Lab 11: Elixirs & Tinctures Mickey Mouse, M.D. 55 PHCY 6101- Dose Form Lab Fall 2010 Method: 1. Using a plastic spatula weigh iodine crystals on a watch glass (iodine stains metals!). Weigh sodium iodide on weighing paper. Careful to not spill any iodine, sodium iodide, or final tincture on benches and your lab coat or clothes (permanent stains on cloth). 2. Measure 15 mL of alcohol and transfer it to a small beaker. Add sodium iodide and stir with glass rod until dissolution. 3. Add iodine and stir until dissolution. 4. Transfer solution to a graduated cylinder or calibrated 1 fl. oz. container (light resistant and tight cap to prevent loss of alcohol). 5. Rinse beaker with purified water and add to the cylinder/calibrated container using enough p. water to complete the volume to 30 mL. Lab 11: Elixirs & Tinctures 56 PHCY 6101- Dose Form Lab Fall 2010 LABORATORY 12 SUSPENSIONS Objectives Practice the preparation of medicated liquid dispersions. Appreciate aggregation of suspended particles, sedimentation, and possible impaction of the sediment as real challenges to a compounding pharmacist. References: Remington's , 21st edition, (2006). Pharmaceutical Dosage Forms and Drug Delivery Systems: H. Ansel, N. Popovich and L. Allen, 8th edition (2005). Allen’s compounded formulations: Loyd V. Allen, Jr, APhA, 2003. Suspensions are preparations containing finely divided drug particles (suspensoid) distributed somewhat uniformly throughout a vehicle (dispersion medium) in which the drug exhibits a minimum degree of solubility. Suspensions are classified as coarse dispersions where the dispersed phase ranges from 1 -100 micron in size. For most oral suspensions, the dispersion medium is aqueous. Because of the nature of the dosage form, pharmaceutical suspensions are basically thermodynamically unstable systems. Aggregation of suspended particles, sedimentation, and possible impaction of the sediment, present real problems to the pharmaceutical formulator. There are certain criteria that a well-formulated suspension should meet. The dispersed particles should be of such a size that they do not settle rapidly in the bottom of the container. However, in the event that sedimentation occurs, the sediment must not form a hard cake. Rather, it must be capable of redispersion with a minimum effort on the part of the patient. Additionally, the product should be easy to pour, pleasant to take, and resistant to microbial attack. The three major problem areas associated with suspensions are (1) adequate dispersion of the particles in the vehicle, (2) settling of the dispersed particles, and (3) caking of these particles in the sediment so as to resist redispersion. The formulation of a suspension possessing optimal physical stability depends on whether the particles in suspension are to be flocculated or to remain deflocculated. One approach involves the use of a structured vehicle to keep deflocculated particles in suspension; a second approach depends on controlled flocculation as a means of Lab 12: Suspensions 57 PHCY 6101- Dose Form Lab Fall 2010 preventing cake formation. The third is a combination of the two previous methods, results in a product with optimum stability. Suspending agents may be used to improve the physical properties of suspension. The small-scale preparation of suspensions may be readily undertaken by the practicing pharmacist with the minimum of equipment. The first step in preparing suspension is trituration, in a mortar, by adding the wetting agent in small increment to the powder. Once the particles have been wetted adequately, the slurry may be transferred to the final container. The next step is addition of dispersion medium and suspending agents. The type of suspending agents to be used depend on whether the deflocculated particles are to be suspended in a structured vehicle then flocculated, or flocculated and then suspended. Conversion of solid dosage forms into a suspension provides an alternative dosage form for a portion of the population who cannot swallow a tablet or capsule. Besides patients who have difficulty swallowing solid dosage forms, there are also patients who cannot swallow due to the placement of a nasogastric tube or any other type of ostomy. Laboratory Exercise 1: Magic Mouth Wash (for stomatitis) Name: Bernice Taylor ℞ Date: Nov. 10, 2010 Antacid (liquid, oral suspension) 1 oz. Diphenhydramine (liquid) 1 oz. Viscous Lidocaine (liquid) 1 oz. M. ft. 3 oz. Sig: ___________________________________________________ Refill: 2 Peter Brown, M.D. Method: • Pre-calibrate a 3 oz. Rx bottle to compound this preparation. • Measure the first two ingredients and pour into the Rx bottle. Cap bottle and shake to mix well. • Add viscous lidocaine; mix. • Label and dispense. * BONUS: Describe how you would counsel this patient to use this prescription. Consider you are doing this in person. Remember to mention to the patient what this prescription was written for, how to use, how frequently, how to report undesirable effects, what to expect as effect. Hand the description of counseling on a sheet of paper at the end of lab for bonus grading. Lab 12: Suspensions 58 PHCY 6101- Dose Form Lab Laboratory Exercise 2: Fall 2010 Ethylaminobenzoate topical suspension (similar benzocaine content as in Anbesol® ointment) Name: Karen Johnson Date: Nov. 10, 2009 ℞ Ethylaminobenzoate Glycerylmonostearate Glycerin (sp.gr.= 1.258) Sodium Lauryl Sulfate Methylparaben Propylparaben P. Water 20% 4.5 g 5.0 g 0.75 g 0.1 g 0.1 g 100 mL q.s. M. ft. suspension 2 fl.oz. Sig: Apply with a cotton swab to the affected area not more than 3 to 4 times daily. Refill: none Bud Tugley, M.D. Method: 1. In a glass mortar triturate ethylaminobenzoate with glycerin until the powder is wet (kind of a thick paste with no clumps). Use plastic spatula to help trituration. Reserve. 2. Heat 10 mL purified water to 55-60° C and dissolve sodium lauryl sulfate with slow stirring (avoid foaming). Reserve. 3. Heat 10 mL purified water to 55-60° C and dissolve the parabens. 4. Combine both aqueous solutions prepared in 2 and 3. Mix well. Reserve. 5. Slowly melt (60° C) glycerylmonostearate in a beaker. 6. Add the warm aqueous phase to the liquid glycerylmonostearate with constant stirring (glass rod only!) until congealing of mixture (creamy appearance and texture). 7. Add by portions the creamy mixture prepared above to the mortar containing ethylaminobenzoate paste. Mix well after each addition. 8. Add 10-15 mL of water to make suspension pourable, mix well and transfer to a 100 mL graduated cylinder. 9. Rinse mortar and pestle with water and use it to complete the prescribed volume of suspension. 10. Transfer product to final container. Label. Suggested auxiliary labels: Shake well before use For external use only Avoid contact with eyes Do not swallow Lab 12: Suspensions 59 PHCY 6101- Dose Form Lab Fall 2010 LABORATORY 13 EMULSIONS Objectives Practice the preparation of medicated liquid dispersions that include 2 immiscible liquids. Understand the importance of emulsifiers and their choice such that the emulsion will possess the maximum stability. Recognize the difference between o/w and w/o emulsions. Practice the preparation of emulsions by dry gum method. References: Remington's , 21st edition, (2006). Pharmaceutical Dosage Forms and Drug Delivery Systems: H. Ansel, N. Popovich and L. Allen, 8th edition (2005). Allen’s compounded formulations: Loyd V. Allen, Jr, APhA, 2003. An emulsion is a dispersion in which the dispersed phase (internal phase) is composed of small globules of a liquid distributed throughout a vehicle/medium (external phase) in which it is immiscible. Emulsions are generally of two types: an emulsion in which the oil is dispersed as droplets throughout the aqueous phase is termed as oil-in-water (o/w) emulsion. When water phase is the dispersed phase and oil the dispersion medium, the emulsion is the water-in-oil (w/o) type. Similarly to suspensions, emulsions are thermodynamically unstable as a result of the excess free energy associated with the surface of the droplets. The dispersed droplets, therefore, strive to come together and reduce the surface area. In addition to this flocculation effect, also observed with suspensions, the dispersed particles can coalesce, or fuse, and this can result in the eventual destruction of the emulsion (braking/cracking). In order to minimize this effect, a third component, the emulsifying agent, is added to the system to improve its stability. The choice of emulsifying agent(s) is critical to the preparation of an emulsion possessing optimum stability, and depends on the type of emulsion to be prepared. Several factors must be taken into account in the successful preparation and formulation of emulsified products: (1) type of emulsion, (2) type of emulsifying agents, (3) incompatibilities of emulsifying agents and other ingredients, and (4) method of preparation. The selection of the emulsifying agent, or agents, is the prime importance Lab 13: Emulsions 60 PHCY 6101- Dose Form Lab Fall 2010 in the successful formulation of an emulsion. The selection mainly depends on the type of emulsion, the hydrophilic-lipophilic balance (HLB), solubility, and compatibility with other ingredients. Traditionally, emulsions have been prepared by the pharmacist using a mortar and pestle. There are mainly two methods to compound an emulsion: (1) wet gum method and (2) dry gum method. In the wet gum method the emulsifying agent is placed in the mortar and dispersed in water to form a mucilage. The oil is added to this mucilage in small amounts with continuous trituration, each portion of the oil being emulsified before adding the next increment. In the dry gum method the gum is added to the oil and then water is added. If the drug is water soluble, it is dissolved in the aqueous phase before addition and if the drug is oil soluble, it is dissolved in oil phase. Laboratory Exercise 1: Trimethoprim and Sulfamethoxazole emulsion (compare to Septra® susp.) Name: James Milles Date: Nov. 17, 2010 ℞ Trimethoprim Sulfamethoxazole Cottonseed Oil Polyoxyethylene Sorbitan-Monostearate (Tween 60) Sorbitan Monooleate (Span 80) Sodium Saccharin Methylparaben Sodium Benzoate Flavor P. Water q.s. 8g 40 g 500 mL 50 mL 84 mL 0.4 g 1.0 g 1.0 g q. s. 1000 mL Ft. 2 oz. Sig: 1 teaspoonful q.i.d. Refill: 0 Jean Carter, M.D. Method: 1. Dry gum method = 4: 2: 1. To prepare 60 mL of this prescription it will be required for the primary emulsion 30 mL of oil, 15 -20 mL of water and 8 g of emulsifier, which corresponds to ~ 4 : 2 : 1. 2. Mix Tween 60 and Span 80 (emulsifying agents) with cottonseed oil in a beaker. Warm to ~ 50°C on a water bath until all clumps are dissolved (oil phase). 3. Add Sulfamethoxazole and mix to dissolve. 4. Remove from heat, cool slightly, and add a flavoring oil. Mix well. Reserve. 5. Dissolve Trimethoprim, saccharin, methylparaben and sodium benzoate in 15-20 mL of water (water phase). 6. Transfer the oil phase to a porcelain mortar and add the aqueous phase all at once with rapid trituration. Lab 13: Emulsions 61 PHCY 6101- Dose Form Lab Fall 2010 7. Using the hand homogenizer add slowly, in divided portions, homogenizing immediately after each addition, the remainder of the aqueous phase (~10-15 mL). 8. Make up the volume with purified water if needed and mix thoroughly. 9. Dispense in a prescription bottle. Laboratory Exercise 2: Mineral Oil emulsion, USP (or Liquid Petrolatum emulsion)-employed as lubricating cathartic. Name: Christine Schmidt ℞ Mineral Oil Acacia Syrup Vanillin Alcohol P. Water Date: Nov. 17, 2010 q.s. 500 mL 125 g 100 mL 40 mg 60 mL 1000 mL Ft. 60 mL Sig: One oz. hs prn constipation Refill: 0 Ralph Holland, M.D. Method: • Mineral oil emulsion is an official compounded emulsion usually prepared by the dry gum method (4: 2: 1 = oil : water : emulsifier). • BONUS: Write down on a sheet of paper, showing the amounts that correspond to 4:2:1 and the method (step-wise) you will use to prepare this emulsion and turn it in at the end of lab. Add your name and lab section. Lab 13: Emulsions 62 PHCY 6101- Dose Form Lab Fall 2010 LABORATORY 14 Final Exam: During the first 60 minutes of lab time. Proceed to lab for check-out after finishing your exam. Lab check-out • • • • • • Using the check-in list, mark all items present in your drawer. All glassware must be clean. Return stir bar to instructor/TA. Make sure broken glassware and disappeared items are restored. Receive your cash deposit after returning locker key to the key cabinet. Make sure you carry away your lab coat and goggles. Lab 14: Final & Check-out 63 ...
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This note was uploaded on 10/15/2010 for the course PHCY 6101 taught by Professor Teixeira during the Fall '10 term at Pima CC.

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