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Suppositories and Inserts -notes-BRIN

Suppositories and Inserts -notes-BRIN - • • • • •...

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Unformatted text preview: • • • • • • • • • • • • • • • Suppositories and Inserts PHCY 6100 Dose Form Design Troy Brin, P4 UW School of Pharmacy October 7, 2010 Suppositories and Inserts Solid dosage forms Intended for insertion into body orifices o Rectal o Vaginal o Urethral (occasionally) Melt, soften, or dissolve Exert local or systemic effects “supponere” (L.) = “to place under” the body Suppositories and Inserts Various sizes, shapes, and weights o Based upon intended orifice o Should be easy to insert without causing undue distention o Once inserted, must be retained for appropriate duration Insertion methods o Fingers – near entrance of orifice o Special appliance – higher/deeper in orifice Especially for vaginal inserts or tablets o Rectal suppositories Adult o Approx. 1.5 inches long o Approx 2g (when compounded with cocoa butter base) o Cylindrical shape, with one or both ends tapered Bullet Torpedo Little finger Pediatric o ½ the weight and size of adult sizes o Pencil-like shape Rectal suppositories Local effects o Relief of constipation (laxatives) o Hemorrhoids (anesthetics) o Anorectal discomfort Systemic effects o Absorption occurs through the mucous membranes of the rectum into the hemorrhoidal veins and lymphatic circulation o Administration of anti-emetics, tranquilizers, anti-inflammatories, anti-pyretics, asthma treatments, others Rectal suppositories Benefits of systemic uses (versus oral route) Delivery of drugs that are destroyed or inactivated by pH or enzymes of stomach or intestines o Delivery of drugs that cause stomach irritation or contribute to vomiting o Delivery of drugs that are destroyed via hepato-portal circulation (1st pass effect) o Delivery of drugs to patients who are unwilling or unable to swallow (children, elderly, comatose) Rectal absorption Primary factors affecting absorption o Constitution of the patient Age, gender, race, disease states, etc. o Physiological barriers that must be traversed o Physico-chemical nature of the drug and base Rectal absorption Physiologic factors o Colonic content An empty rectum allows maximum drug absorption Diarrhea, tumors of the rectum, colonic obstructions, and dehydration all may decrease rate and extent of absorption o Circulation route Bypass liver (1st pass effect) • Lower hemorrhoidal veins – absorbs majority • Lymphatic system surrounding colon o PH and buffering capacity Rectal fluids are pH-neutral • No buffering capacity • Drug is not chemically altered – must be in active form Rectal absorption Physico-chemical factors o Lipid-water solubility Partition coefficient of the drug is important when considering an appropriate base • Drugs in ionized form (charged) are less likely to traverse membranes o Particle size Smaller particles have better/faster dissolution and absorption o Nature of the base Qualities of a good suppository base • Melt at body temperature or soften/dissolve in body fluids • Readily release the drug for absorption o A lipophilic drug in fatty base in low concentration less likely to distribute than a hydrophilic drug in a fatty base • Be non-irritating to mucosal membranes (exception: laxatives) Vaginal suppositories Also called pessaries (Fr.) = tampons Approx 5g (if compounded with cocoa butter base) Typical shapes o Globular o Oviform o • • • • • • • • • • Cone Vaginal suppositories Typically buffered to pH of 4.5 (pH of normal vagina) Frequently come with insertion device Local effects o Contraceptives (nonoxynol-9) o Feminine hygiene (antiseptics) o Treatment of vaginitis/pathogens Trichomonas vaginalis Candida albicans Haemophilus vaginalis Systemic effects o Not typically used Urethral suppositories Also called bougies (Fr.) = candles Slender, pencil-shaped Typical sizes for males: o Approx 60-140mm long o Approx 3-6mm in diameter o Approx 4g (if compounded with cocoa butter base) For females: o Typically half the length and weight of those for males Uses: o Erectile dysfunction (MUSE® alprostadil) in males o Genitourinary infections o Pre-operative local anesthesia Suppository Bases Two main/primary categories o Fatty or oleaginous bases o Water-soluble and water-miscible bases Miscellaneous category o Consists of combinations of lipophilic and hydrophilic substances Fatty or oleaginous bases Most frequently employed type of base Solid at room temperature Melt at body temperature to release drug Examples: o Cocoa butter o Hydrogenated vegetable oils o Glycerin mixed w/ higher-molecular weight fatty acids o Fattibase o Wecobee bases o Witepsol bases Cocoa butter Cocoa butter o fat from roasted seed of Theobroma cacao o Most often used suppository base o • • • • • • • • • • • • • • • • • • • • Yellowish solid with a chocolate odor Chemically a triglyceride (combo of glycerin + fatty acid) Melts at 86-97oF Melt slowly in water bath - polymorphism characteristics Alpha form unlikely to harden/solidify at room temp Beta form preferred (more stable form) o Some substances may lower its melting point Phenol and chloral hydrate o Solidifying agents may be added Cetyl esters wax, bees wax Water-soluble or water-miscible bases Glycerinated gelatin o Common: 20% gelatin + 70% glycerin + 10% H2O or drug Glycerin adds elasticity to the gelatin o Slower to soften/mix with physiologic fluids vs. cocoa butter, providing a slower release of drug o Frequently used in cases where prolonged local action of the medication is desired, such as vaginal suppositories o Frequently used for urethral suppositories due to cocoa butter’s brittleness and rapid melting at body temp o Have a tendency to absorb moisture from environment Must be protected/sealed to maintain shape and consistency May have a dehydrating effect and irritate tissues • Moisten with water prior to insertion Water-soluble or water-miscible bases Polyethylene glycols (PEGs) o Most popular water-soluble base type o Polymers of ethylene oxide + H2O o Variety of chain lengths, molecular weights, and physical states o Number following PEG indicates molecular wt <= 600 are clear, colorless liquids >= 1000 are wax-like white solids Melting temp increases as molecular wt increases Two or more PEGs may be “fused” to create a base with desired consistency and characteristics o PEG suppositories are not designed to melt at body temp Designed to dissolve in body fluids Provide for slower drug release Do not easily melt in warm environments Do not leak from orifices May have a dehydrating effect and irritate tissues if <20% H2O content • Moisten with water prior to insertion Preparation of suppositories Three common methods o Molding from a melt (fusion) o Compression o Hand rolling and shaping o o o o • • • • • • • • • • • • Preparation of suppositories Method #1 – Molding from a melt o A sufficient amt of base is melted (use lowest possible heat) o Active drug ingredients are incorporated o Three methods for calculating amt of base that the drugs displace Dosage replacement factor method Density factor method Occupied volume method o Melt is poured into molds Mold may require pre-lubrication if water-soluble base is used Molds require calibration due to variances in the specific gravity of each base type and the medications added o Molds allowed to cool and suppositories congeal/solidify o Suppositories are removal from mold and trimmed o Molds may be cleaned/reused or disposable Preparation of suppositories Method #2 – Compression o Base and active drug ingredients are combined via mortar & pestle (friction will soften base to paste-like consistency) o Pressed into dies via manual/automated machine o Prepared without heat o Advantages: Useful for heat-labile medications or substances that are insoluble in the base Little likelihood of insoluble matter settling during manufacturing o Disadvantages: Requires special compression machine Limitation on the shapes/sizes that can be made • Each size/shape requires a its own machine dies Preparation of suppositories Method #3 - Hand rolling and shaping o Requires skill (seldom performed by modern RPh) o Prepared without heat o Generally uses cocoa butter Cocoa butter is grated Active ingredient(s) are mixed in • Using a mortar & pestle or ointment slab Mixture is pressed until it resolidifies Mixture then shaped into a long cylinder with desired diameter Suppositories are cut into desired length ...
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