Capsule

1. Introduction Latin word Capsula means “ the small box ”.“Capsules are unit solid dosage forms in which one or more medicinal and or inert substances are enclosed in either a hard or soft soluble container or shell of a suitable form of gelatin.” As per US Pharmacopoeia : “Capsules are defined as solid dosage forms in which the active ingredients are sealed in a hard or soft container or shell.” The USP also mentions starch and other substances used in the production of the shell. As per European Pharmacopoeia : “Capsules are solid preparations with hard or soft shells of various shapes and capacities, usually containing a single dose of active ingredient. They are intended for oral , vaginal rectal, administration.”

2. Advantages of capsules • May be swallowed whole and easily taken by the patient. • Tasteless when swallowed and mask the unpleasant taste/odor of the drug. • The contents may be removed from the gelatin shell and employed as a pre measured medicinal powder, the capsule shell being use to contain a dose of the medicinal substance. • Elegance . • Commonly embossed or imprinted on their surface the manufacturer’s name and product code readily identified. • Available in variety of dosage strength . • Portability. • Provide flexibility to the prescriber and accurate individualized dosage for the patient. • Packaged and shipped by manufacturers at lower cost less breakage than liquid forms. • Achieve modified drug release.

3. Advantages of capsules The formulation of capsules may be preferred for several reasons • The use of capsules avoids many unit operations that are associated with the manufacture of tablets, e.g. compression, granulation, drying. • Capsules (generally soft gelatin capsules) may be formulated to increase the oral bioavailability of poorly soluble therapeutic agents. This is particularly the case when formulated as a liquid-filled hard gelatin or soft gelatin capsule. • Encapsulation of various kind of material efficiently and productively. • Capsules are a convenient method by which liquids may be orally administered to patients as a unit dosage form. • The stability of therapeutic agents and longer shelf life may be improved in a capsule formulation. • Capsules are a convenient means of formulating substances of abuse.

4. Disadvantages of capsule The disadvantages of capsule formulations include • The requirement for specialized manufacturing equipment. • Potential stability problems associated with capsules containing liquid fills. • Problems regarding the homogeneity of fill weight and content may be associated with capsule formulations. • Extreme dryness- capsules may become brittle and crumble.

5. Components of capsules Raw Materials for Capsules The raw materials used in the manufacture of both hard and soft gelatin capsules are often similar. Capsules may contain additional ingredients such as Preservative , FD & C and D & C colorant Opacifying agents, Flavorings, Sugars, Acids & Medicaments …………….. to achieve desired effects.

6. Components of capsulesshell • Water -- N.M.T 45% w/w. The ratio by weight of water to dry gelatin can vary from 0.7 to1.3 (water) to 1.0 (dry gelatin) depending on the viscosity of the gelatin being used . Empty capsule contain a significant amount of water (HGC is between 13% to 16% w/w) that acts as plasticizer for the gelatine film and is essential for their function. • Gelatin-- Obtain from partial hydrolysis of collagen derived from the skin, connective tissue & Bones of animals. • Plasticizer-- Used to make the soft gel shell elastic & pliable. Ratio used is between 0.3 to 1.8 for soft to hard shell on dry basis. E.g. glycerin , sorbitol . • Colour-- Used in shell has to be darker than colour of encapsulating material. Colours may be natural or synthetic. • Opacifier-- Usually Titanium dioxide, may be added to produce an opaque shell , when the fill formulation is a Suspension or to prevent photo degradation of light sensitive fill ingredients. • Conc. Of opacifier may be up to 0.5% . Sulfur dioxide (.15%) - prevent decomposition during manufacture.

7. Capsule size • Generally, hard gelatin capsule are used to encapsulate between 65 mg to 1 gram. • How to select capsule size? • The amount of fill material to be encapsulated. • The density and compressibility of the fill . • The final determination largely may be the result of trial. The sizes of empty capsules For human use : 000 (the largest), 00, 0, 1, 2, 3, 4, 5 (the smallest) For veterinary use : Larger capsules are available.

8. Capsule shape

9. Gelatin • Gelatin is tasteless clear , jelly or film like substance obtained by the partial hydrolysis or boiled of collagen obtained from skin, white connective tissue and bones of animals. Available in the form of a fine powder, a coarse powder, shreds, flakes, or sheets. • Gelatin is insoluble in cold water and soluble in hot water and in warm gastric fluid up to ten times its weight . Gelatin being a protein, is digested by proteolytic enzymes and absorbed. • Stable in air when dry but when become moist - subject to microbial decomposition. • HGC contain 13 to 16 % of moisture. Extreme dryness- capsules (Gelatin) may become brittle and crumble. Prolong exposure to high humidity can affect in vitro capsules (Gelatin) dissolution.

10. (12.7cm) in diameter approximately five days Roasted for approximately 30 minutes at about (100° C). Reduce the fat content to about 2% into large aluminum extractors 4% hydrochloric acid with a pH of less than 1.5 . Alkaline wash is a potassium or sodium carbonate with a pH above 7.

11. Removes most of the minerals and bacteria and facilitates the release of collagen . About (140° C) for approximately four seconds Sweeteners, flavorings, colorings may be added

12. Hard gelatin capsules • Hard gelatin capsules also referred to as “DFC” Dry Filled Capsule. • Manufactured into two sections, the capsule body and a shorter cap. • Hard gelatin capsules usually use in the extemporaneous compounding of Rx. • Hard gelatin capsules shell is made of gelatin, sugar, and water. • Clear, essentially tasteless , colorless orColored with various fd & c and d & c dyes and made opaque by adding agents such as titanium dioxide. Combination of colorants and opaquants to make them distinctive, many with caps and bodies of different colors. Application of hard gelatin capsules • Used to manufacture most medicated agents. • Employed in clinical trials. • Used in the extemporaneous compounding. A recent innovation in capsule shell design is the Snap-Fit, Coni-Snap hard gelatin capsules.

13. Manufacturing Process of Capsule

14. Quality control The main quality control item of gelatin • Viscosity degradation • Moisture • Transparency • Ash • Ph value

15. Soft gelatin capsules Soft gelatin (also called softgel or soft elastic) capsules consist of one-piece hermetically-sealed soft shells. Soft gelatin capsules are made of gelatin, glycerin (or a polyhydric alcohol such as sorbitol) and water etc. encapsulate non-aqueous liquids, suspensions, pasty materials, dry powders and even preformed granules, pellets, tablets. They are especially important to contain volatile drug substances or drug materials susceptible to deterioration in the presence of air. The plasticizer makes gelatin elastic. Soft gelatin capsules come in various shapes such as spherical, elliptical, oblong, and special tube shapes with and without twist off .

16. The pharmaceutical applications of soft gelatin capsules The pharmaceutical applications of soft gelatin capsules are--- 1) As an oral dosage form 2) As a suppository dosage form 3) As a specialty package in tube form, for human and veterinary single dose Application of topical, ophthalmic, and otic preparations, and rectalointments. 1. Acetazolamide - Carbonic anhydrase inhibitor 2. Cyclosporine - Immunosuppressive 3. Cyclosporine - Immunosuppressive 4. Digoxin - Cardiac glycoside 5. Ethosuximide - Anticonvulsant Ranitidine HCl - Histamine H2 receptor inhibitor

17. Advantages of soft gelatin capsules • Ease of swallowing • Dosage accuracy/uniformity: Precise fill volume of liquid fill unit delivers a greater degree of accuracy and consistency from capsule-to-capsule and lot-to-lot. • Consistent manufacturing requirements: More accurate compounding, blending, and dispensing of liquid fill facilitates manufacturing. Liquid blends are more homogeneous. • Increase in bioavailability: Absorption and bioavailability can be enhanced by formulating compounds in solution including solubilizers and absorption enhancers, if necessary. Water-insoluble drugs may be formulated in a softgel. Clinical studies have shown enhanced absorption and bioavailability with softgel forms.

18. Advantages of soft gelatin capsules Enhanced stability and security: The tight hermetical sealing protects fill from air and environmental contamination. Gelatin shell can be formulated to block out ultraviolet light. Streamlined, one-piece design is tamper-evident. Pliable shell: soft gel shell allows for custom shapes and sizes ap-propriate for oral, topical, chewable and suppository delivery. Portability: Encapsulated liquid dosage formulations become highly portable for consumers/patients .

19. Disadvantages of soft gel capsules 1. Requires special manufacturing equipment 2. Stability concerns with highly water soluble compounds, and compounds susceptible to hydrolysis 3. Limited choices of excipients/carriers compatible with the gelatin

20. Storage of capsule Containers 1) Light resistant container 2) Well-closed container 3) Tight container 4) Hermetic container Preservation conditions 1)Freezer: -25 ~ -10 ℃; 2)Cold: <8 ℃; 3)Cool: 8 ~ 15 ℃; 4)Room Temperature: The temperature prevailing in a working area. 5)Controlled Room Temperature: 20 ~ 25 ℃; 6)Warm: 30 ~ 40 ℃; 7)Excessive Heat: >40 ℃; 8)Protection from Freezing: (breakage of the container, loss of strength or potency, destructive alteration of its characteristics).

21. Packaging and storage of capsules Capsules should be packed in a well-closed glass or plastic containers and stored in a cool place. These type of containers have advantage over cardboard boxes that they are more convenient to handle and transport and protect the capsules from moisture and dust. To prevent the capsules from rattling a tuft of cotton is placed over and under the capsules in the vials. In vials containing very hygroscopic capsules a packet-containing desiccant like silica gel or anhydrous calcium chloride may be placed to prevent the absorption of excessive moisture by the capsules. Now a days capsules are strip packaged which provide sanitary handling of medicines, ease in counting and identification. Empty gelatin capsules should be stored at room temperature at constant humidity. High humidity may cause softening of the capsules and low humidity may cause drying and cracking of the capsules. Storage of capsules in glass containers will provide protection not only from extreme humidity but also from dust. Storage of filled capsules is dependent on the characteristics of the drugs they contain. Semisolid filled hard gelatin capsules should be stored away from excessive heat, which may cause a softening or melting of the contents.

22. Properties of the final capsule The final capsules should exhibit a water content of 13–16% w/w. This is an important consideration in light of the effects of water content on the mechanical (and hence in-use) properties of the capsules. Water acts as a plasticiser for gelatin to ensure that the mechanical properties of the capsule are sufficiently robust so that the capsule does not either crack or permanently deform during manufacture, handling or storage. If the water content is lower than the above specification, the capsule shell will become brittle and will crack when exposed to the appropriate stress. Conversely, if the water content is excessive, the capsule will undergo plastic flow upon exposure to stress and will lose shape. It is therefore important that the desired water concentration in the capsule is achieved within the drying phase of the manufacturing process. It is additionally preferable that capsules should be stored under conditions that do not adversely affect this parameter.