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Capsule
The document provides a comprehensive overview of capsules as solid dosage forms used for medication, highlighting their advantages such as accurate dosing, ease of use, and cost-effectiveness. It details the manufacturing processes of hard and soft gelatin capsules, including formulation, filling, sealing, and testing requirements, while also discussing stability and inspection protocols. Additionally, it outlines compendial standards for capsules, emphasizing the importance of quality control and bioavailability in pharmaceutical applications.
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Capsule
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- 2. Characters 1) orally, convenientlycarried, readily identified, and easily taken 2) compared with equivalent doses of a liquid medication, accurate dosing, most tasteless when swallowed 3) readily identified 4) Prescribing flexibility (a variety of dosage strengths)
- 3. 5) from apharmaceutic standpoint, solid dosage forms are • efficiently and productively manufactured • packaged and shipped by manufacturers at lower cost and with less breakage than comparable liquid forms • more stable, have a longer shelf-life than their liquid counterparts.
- 4. I. Capsules 1. Hardgelatin capsules 2. Soft gelatin capsules 3. Compendial requirements for capsules 4. Official and commercially available capsules 5. Inspecting, counting, packaging, and storing capsules
- 5. Capsules are soliddosage forms in which medicinal agents and/or inert substances are enclosed in a small shell of gelatin. Gelatin capsule shells may be hard or soft, depending on their composition.
- 6. 1. Hard gelatincapsules • Hard gelatin capsule shells are used in most commercial medicated capsules. • The empty capsule shells are made of gelatin, sugar, and water. • They can be clear, colorless, and essentially tasteless; or they may be colored with various dyes.
- 7. • Most commerciallyavailable medicated capsules contain combinations of colorants and opaquants to make them distinctive, many with caps and bodies of different colors. • Gelatin is obtained by the partial hydrolysis of collagen obtained from the skin, white connective tissue, and bones of animals.
- 8. • It isdesirable to maintain hard gelatin capsules in an environment free from excessive humidity or dryness. • Many capsules are packaged along with a small packet of a desiccant material to protect against the absorption of atmospheric moisture. The desiccant materials most used are dried silica gel, clay, and activated charcoal.
- 9. • A numberof methods have been developed to track the passage of capsules and tablets through the gastrointestinal tract to map their transit time and drug release patterns. • Among these is gamma scintigraphy, a noninvasive procedure that entails use of a gamma ray-emitting radiotracer incorporated into the formulation with a gamma camera coupled to a data recording system.
- 10. When scintigraph iscombined with pharmacokinetic studies, the resultant pharmacoscintographic evaluation provides information about the transit and drug release patterns of the dosage form as well as the rate of drug absorption from the various regions of the gastrointestinal tract.
- 11. This method isparticularly useful in (a) determining whether a correlation exists between in vitro and in vivo bioavailability for immediate-release products, (b)assessing the integrity and transit time of enteric coated tablets through the stomach en route to the intestines, (c) drug and dosage form evaluation in new product development.
- 12. 1) The manufactureof hard gelatin capsule shells • Hard gelatin capsule shells are manufactured in two sections, the capsule body and a shorter cap. • The shells are produced industrially by the mechanical dipping of pins or pegs of the desired shape and diameter into a temperature-controlled reservoir of melted gelatin mixture.
- 14. • The pegssubmerged to the desired depth and maintained for the desired period to achieve the proper length and thickness of coating. • The pegs are slowly lifted from the bath and the gelatin dried by a gentle flow of temperature- and humidity-controlled air. • When dried, each capsule part trimmed mechanically to the proper length and removed from the pegs, and the capsule bodies and caps are joined together.
- 15. 2) Capsule sizes •Empty gelatin capsules are manufactured in various lengths, diameters, and capacities. • The size selected for use is determined by the amount of fill material to be encapsulated. • The density and compressibility of the fill will largely determine to what extent it may be packed into a capsule shell.
- 17. 3) Preparation offilled hard gelatin capsules • Developing and preparing the formulation and selecting the size capsule • Filling the capsule shells • Capsule sealing (optional) • Cleaning and polishing the filled capsules
- 18. 4) Developing theformulation and selection of capsule size In developing a capsule formulation, the goal is to prepare a capsule with • accurate dosage, • good bioavailability, • ease of filling and production, stability, and elegance.
- 19. • In dryformulations, the active and inactive components must be blended thoroughly to ensure a uniform powder mix for the fill. • A diluent or filler (lactose, microcrystalline cellulose and starch) may be added to the formulation to produce the proper capsule fill volume.
- 20. • Disintegrants (pregelatinizedstarch, croscarmellose and sodium starch glycolate) are frequently included in a capsule formulation to assist the breakup and distribution of the capsule’s contents in the stomach. • To achieve uniform drug distribution, it is advantageous if the density and particle size of the drug and nondrug components are similar.
- 21. • The additionof a lubricant or glidant such as fumed silicon dioxide, magnesium stearate, calcium stearate, stearic acid, or talc (about 0.25-1%) to the powder mix enhances flow properties. • A surface-active agent, such as sodium lauryl sulfate, is used to facilitate wetting by the gastrointestinal fluids.
- 22. • Gelatin capsulesare unsuitable for aqueous liquids because water softens gelatin and distorts the capsules, resulting in leakage of the contents. • A liquid may be mixed with an inert powder to make a wet mass or paste, which may then be placed in capsules in the usual manner.
- 23. • Eutectic mixturesof drugs, or mixtures of agents that have a propensity to liquefy when admixed, may be mixed with a diluent or absorbent to separate the interacting agents and to absorb any liquefied material that may form.
- 25. The selection ofthe capsule size
- 26. • Hard gelatincapsules are used to encapsulate between about 65 mg and 1 g of powdered material. • The smallest capsule (No. 5) may be expected to hold 65 mg of powder or more, depending on the characteristics of the powder substance.
- 27. An example ofcommercially available capsule: • Active ingredient: tetracycline hydrochloride 250 mg • Filler: lactose • Lubricant/glidant: magnesium stearate • Capsule colorants: FD&C Yellow No. 6 • Capsule opaquant: Titanium dioxide
- 28. 5) Filling hardcapsule shells
- 30. 6) Capsule sealing •Sealed with gelatin • Sealed through a heat welding process that fuses the capsule cap to the body through the double wall thickness at their juncture • Utilized a melting-point-lowering liquid wetting agent in the contact areas of the capsule’s cap and body and then thermally bonds the two parts using low temperatures (40-45C).
- 32. 7) Cleaning andpolishing capsules • On a small scale, capsules may be cleaned individually or in small numbers by rubbing them with a clean gauze or cloth. • On a 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.
- 35. 2. Soft gelatincapsules • Soft gelatin capsules are made of gelatin to which glycerin or a polyhydric alcohol such as sorbitol has been added. • Soft gelatin capsules, which contain more moisture than hard capsules, may have a preservative, such as methylparaben and/or propylparaben, to retard microbial growth. • Soft gelatin capsules may be oblong, oval, or round.
- 36. 1) Preparation ofsoft gelatin capsules Soft gelatin capsules may be prepared • by the plate process, using a set of molds to form the capsules. • by the rotary or reciprocating die processes by which they are produced, filled, and sealed in a continuous operation. • Most soft gelatin capsules are prepared by the rotary die process.
- 37. By the plateprocess, 1) A warm sheet of plain or colored gelatin is placed on the bottom plate of the mold and the liquid-containing medication is evenly poured on it. 2) A second sheet of gelatin is carefully placed on top of the medication and the top plate of the mold is put into place. 3) Pressure is then applied to the mold to form, fill, and seal the capsules simultaneously 4) The capsules are removed and washed with a solvent harmless to the capsules.
- 38. By the rotarydie process, 1) Liquid gelatin flowing from an overhead tank is formed into two continuous ribbons by the rotary die machine and brought together between twin rotating dies. 2) At the same time, metered fill material is injected between the ribbons precisely at the moment that the dies form pockets of the gelatin ribbons.
- 39. 3) These pocketsof fill-containing gelatin are sealed by pressure and heat and then severed from the ribbon. 4) Use of ribbons of two different colors results in bicolored capsules.
- 40. The reciprocating dieprocess is similar to the rotary process in that ribbons of gelatin are formed and used to encapsulate the fill, but it differs in the actual encapsulating process. 1) The gelatin ribbons are fed between a set of vertical dies that continually open and close to form rows of pockets in the gelatin ribbons. 2) These pockets are filled with the medication and are sealed, shaped, and cut out of the films. 3) As the capsules are cut from the ribbons, they fall into refrigerated tanks which prevent the capsules from adhering to one another.
- 41. 2) Utilization ofsoft gelatin capsules • Soft gelatin capsules are prepared to contain a variety of liquid, paste, and dry fills. • Liquids that may be encapsulated into soft gelatin capsules include the following:
- 42. - water-immiscible volatileand nonvolatile liquids such as vegetable and aromatic oils, aromatic and aliphatic hydrocarbons, chlorinated hydrocarbons, ethers, esters, alcohols and organic acids.
- 43. - water-miscible, nonvolatileliquids, such as polyethylene glycols, and nonionic surface active agents as polysorbate 80. - water-miscible and relatively nonvolatile compounds, as propylene glycol and isopropyl alcohol, depending on factors as concentration used and packaging conditions.
- 44. • Liquids arenot suitable for soft gelatin capsules. These materials include - water above 5% - low molecular weight water-soluble and volatile organic compounds such as alcohols, ketones, acids, amines, and esters.
- 45. 3. Compendial requirements forcapsules 1) Requirements for added substances - Harmless - Do not impair the product’s bioavailability, therapeutic efficacy or safety - Do not interfere with requisite compendial assays and tests - Do not exceed the minimum amounts required to provide their intended effect
- 46. 2) Containers fordispensing capsules The container may be required to be tight, well-closed, and light resistant. 3) Disintegration tests for capsules The capsules are placed in the basket rack assembly, which is immersed 30 times per minute into a thermostatically controlled fluid at 37C. The capsules disintegrate completely into a soft mass.
- 47. 4) Dissolution testfor capsules The dissolution test for capsules uses the same apparatus, dissolution medium, and test as that for uncoated and plain coated tablets. 5) Weight variation The uniformity of dosage units may be demonstrated by determining weight variation and/or content uniformity. - hard capsules - Soft capsules
- 48. HARD CAPSULES: • Tencapsules are individually weighed and the contents removed. • The emptied shells are individually weighed and the net weight of the contents calculated by subtraction. • From the results of an assay performed as directed in the indidual monograph, the content of active ingredient in each of the capsules is determined.
- 49. SOFT CAPSULES: • Thegross weight of 10 intact capsules is determined individually. • Each capsule is cut open with a scissors or a sharp open blade, and the contents removed by washing with a suitable solvent. • The solvent is allowed to evaporate at room temperature over a period of about 30 minutes, taking precautions to avoid uptake or loss of moisture. • The individual shells are weighed and the net contents calculated. • From the results of the assay directed in the individual monograph, the content of active ingredient in each of the capsules is determined.
- 50. 6) Content uniformity -The amount of active ingredient, determined by assay, is within the range of 85% to 115% of the label claim for 9 of 10 dosage units assayed, with no unit outside the range of 70% to 125% of label claim. - Additional tests are prescribed when two or three dosage units are outside of the desired range but within the stated extremes.
- 51. 7) Content labelingrequirement All official capsules must be labeled to express the quantity of each active ingredient in each dosage unit.
- 52. 8) Stability testing Stabilitytesting of capsules is performed to determine - the intrinsic stability of the active drug molecule, - the influence of environmental factors as - temperature, - humidity, - light, - formulative compounds - the containers/closure system.
- 53. The battery of •stress testing, • long-term stability • and accelerated stability tests help determine the appropriate conditions for storage and the product’s anticipated shelf-life.
- 54. 9) Moisture permeationtest The degree and rate of moisture- penetration of containers are determined - by packaging the dosage unit together with a color-revealing desiccant pellet, - exposing the packaged unit to known relative humidity over a specified time, - observing the desiccant pellet for color change (indicating absorption of moisture) - comparing the pre- and post-weight of the packaged unit.
- 55. 4. Official andcommercially available capsules • There are approximately 200 officially recognized medications in capsule form in the USP. • However commercially, there are many fold this number of capsule products available from various manufactures for various drugs and in various dosage strengths.
- 56. 5. Inspecting, packagingand storing capsules • Capsules produced on a small or large scale should be uniform in appearance. • Visual or electronic inspection should be undertaken to detect any flaws in the integrity and appearance of the capsules.
- 57. • Capsules arepackaged in glass or in plastic containers, some containing packets of a desiccant to prevent the absorption of excessive moisture. • Capsules should be stored in tightly capped containers in a cool, dry place.