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Unformatted text preview: Capsules Can be colored with dyes or opaque (titanium dioxide) Moisture – 13‐16% Higher moisture: absorbed by caps – become distorted and lose rigid shape Very low humidity (high dryness): moisture lost – become brittle and crumble Package with desiccant to avoid excess or to lower the humidity Gelatin Insoluble in cold water Soluble in hot water and in warm gastric fluid Protein, so digested by proteolytic enzymes and absorbed Manufacturing of shells Two sections – body and cap: overlap when joined with cap fitting snugly over the open end of the body Taper ends to avoid splitting Pegs made of manganese bronze Capsule sizes Determined by the amount of fill material to be encapsulated *density and compressibility of fill will largely determine to what extent it may be packed into capsule shell ‐ initial judgment to approximate size Final determination: use of trial and error Human sizes range from Size 000 (largest) to 5 (smallest) Can have a single medicinal agent or a combo of stuff Preparation of filled hard gelatin capsules: large or small scale 1. Developing and preparing the formulation and selecting the size capsule 2. Filling the capsule shells 3. Capsule sealing (optional) 4. Cleaning and polishing the filled capsules. Developing the formulation and selection of capsule size Goal: prepare a capsule with accurate dosage, good bioavailability, ease of filling and production, stability and elegance Dry formulations: powders mix thoroughly – uniform powder mix especially important in low dose drugs Diluents/fillers: lactose, microcrystalline cellulose, & starch for bulk and cohesion to the powders (beneficial in transferring mixture into caps) Disintegrants: pregelatinized starch, croscarmellose, & sodium starch glycolate used to assist the breakup and distribution of the capsule contents in the stomach. Uniform drug distribution: want this & to achieve – density and particle size of drug & non‐drug similar. Can reduce particle size via milling (50‐1000µm) and can be done with 10mg or greater of drug. Lower dose (less than 10mg) or when smaller particles needed – micronization is used to get particle size to 1‐20µm. Industry: use lubricant or glidant: fumed silicon dioxide, magnesium stearate, calcium stearate, stearic acid or talc (about 0.25 to 1%) – enhances flow properties 1 Magnesium stearate is water‐insoluble, thus can retard penetration by GI fluids and delay drug dissolution and absorption. So when used as a lubricant, a surface‐active agent such as sodium lauryl sulfate, is used to facilitate wetting by the GI fluids. Each ingredient can influence the bioavailability of the drug and a pharmacist must be aware of this. Inserting tablets or small capsules into capsules is sometimes useful: 1) to separate chemically incompatible agents 2) to add premeasured amounts of potent drug substances. Gelatin – unsuitable for aqueous liquids because water softens gelatin and distorts the capsules, resulting in leakage of the contents Some liquids such as fixed or volatile oils, that do not interfere with the stability of the gelatin caps may be placed in locking gelatin caps to ensure retention of the liquid. Rather than placing a liquid in a cap the liquid can be mixed with a powder to make a wet mass or paste, which can then be placed in the cap Eutectic mixtures: mixture of substances/drugs that have a propensity to liquefy when admixed Mix with diluents or absorbent such as magnesium carbonate, kaolin, or light magnesium oxide to separate interacting agents and to absorb any liquefied material that may form. Most the time the amount in a cap is a singles dose unless dose too large to fit in capsule Selection of capsule size (commercial product): Requirements of the formulation – dose of active ingredient; and density and compaction characteristics of the drug and other materials. Hard gelatin caps: Encapsulate 65mg to 1g of powdered material Filling Hard Capsule Shells Punch method Small number of caps in the pharmacy Obtain exact number of caps needed for Rx Place powder on clean sheet of paper Using the spatula – the powder mix is formed into a cake having a depth of approx ¼ to 1/3 the length of the capsule body Empty cap held between thumb and forefinger and punched vertically into the powder cake repeatedly until filled (slight resistance). Wear gloves to avoid contaminating caps Can weigh cap to determine amount of compaction needed Potent drugs – each cap should be weighed Granular material may be poured or scooped into capsule Hand operated filling machine 24 to 300 capsules 200 to 2000 capsules per hour 2 Industrial machines Automatically separate the caps from empty capsules, fill the bodies, scrape off the excess powder, replace the caps, seal the capsules as desired, and clean the outside of the filled capsules at up to 165,000 capsules per hour. Capsules Sealing For tamper‐resistance/evident Seal the joint btwn the two capsule parts Colored band of gelatin Heat welding process that fuses the capsule cap to the body through the double wall thickness at their junction – distinctive ring around the capsule where heat welded Liquid wetting agent that lowers the melting point in the contact areas of the capsule’s cap and body and then thermally bonds the two parts using low temperatures For extemporaneously prepared caps: Seal by lightly coating the inner surface of the cap with a warm gelatin solution immediately prior to placement on the filled capsule body Cleaning and Polishing Capsules Small amts of powder may adhere to outside of caps after filling – powder may be bitter or unpalatable Should remove this to assist in patient compliance Small scale: Capsules cleaned individually or in small numbers by rubbing them with a clean gauze or cloth Large scale: Many capsule‐filling machines are affixed with a cleaning vacuum that removes any extraneous material from the capsules as they exit the equipment SOFT GELATIN CAPSULES Made of gelatin in which glycerin or a polyhydric alcohol such as sorbitol has been added. More moisture than hard caps May have a preservative, such as methylparaben and/or porpylparaben, to retard microbe growth Can be oblong, oval, or round Single color or two‐toned Can be imprinted Can be prepared with opquants to reduce transparency Used to encapsulate and hermetically seal liquids, suspensions, pasty materials, dry powders, and even preformed tablets. Preparation: very specialized equipment (plate process or rotary/reciprocating die processes) Compendial Requirements Added substances Containers Disintegration test Dissolution test Weight variation Content uniformity Content labeling Stability testing Moisture permeation test 3 ...
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This note was uploaded on 10/15/2010 for the course PHCY 6100 taught by Professor Teixeira during the Fall '10 term at Wyoming.
- Fall '10