Hard gelatin capsules

Hard gelatin capsules

1. Mr Nandakishor B Deshmukh Assistant Professor Department of Pharmaceutics Shraddha institute of Pharmacy, kondala zambre , washim CAPSULES 7/8/2023 PROF N.B.DESHMUKH 1

2. CAPSULES Introduction Capsules are solid dosage forms in which one or more medicinal and inert ingredients are enclosed in a small shell or container (usually of gelatin). They are of various shapes and sizes and contain a single dose of one or more active ingredients. They are intended for oral administration. Capsules are also defined as “ gelatin or methylcellulose shell designed to hold solids and liquids for oral administration 7/8/2023 PROF N.B.DESHMUKH 2

3. *There are two types of capsules, i.e., hard and soft . The hard capsule is also called two piece as it consists of two pieces in the form of small cylinders closed at one end. The shorter piece is called the cap which fits over the open end o f the longer piece, called the body. Hard capsules are intended to contain solids . The soft gel atin capsule is also called as one piece and is intended to hold liquids. Capsules are available in many sizes to provide dosing flexibility. Unpleasant drug tastes and odours can be masked by the tasteless gelatin shell. Capsules are solid preparations with hard and soft shells of various shapes and capacities, usually containing a single dose of active ingredients.   7/8/2023 PROF N.B.DESHMUKH 3

4. Types of Capsules Hard Gelatin Capsules A base containing plasticiser and water is utilised to manufacture hard capsules. Preservatives, colours , flavours , and s ugars may also be present in the base. Soft Gelatin Capsules A liquid gelatin is utilised to manufacture soft capsules or liquid gel caps. The liquid gelatin is later hardened in a humid environment. Generally, these capsules are a continuous piece of gelatin. 7/8/2023 PROF N.B.DESHMUKH 4

5. Advantages The advantages of capsules are: They are tasteless, odourless , and can be easily administered. They are attractive in appearance. The drugs having unpleasant odour and taste are enclosed in a tasteless shell. They can be filled quickly and conveniently, therefore, the physician can change the dose and combination of drugs to suit the individual patient (this is an advantage over tablets). The solubility of gelatin at gastric pH provides rapid release of in the stomach. They are economical. They are easy to handle and carry. They require minimum excipients. Little pressure is required to compact the material. 7/8/2023 PROF N.B.DESHMUKH 5

6. Disadvantages The disadvantages of capsules are: The hygroscopic drugs are not suitable for filling into capsules as they will absorb the water present in capsule shell, rendering the shell very brittle and ultimately leading it to crumble into pieces. The concentrated solutions which require previous dilution are unsuitable for capsules because if administered as such it will lead to stomach irritation. The capsules are not suitable for highly soluble substances like potassium chloride, potassium bromide, ammonium chloride, etc. They are also not suitable for highly efflorescent or deliquescent materials. They demand special storage conditions.  7/8/2023 PROF N.B.DESHMUKH 6

7. HARD GELATIN CAPSULES Introduction Hard capsules have a rigid shell in two separate pieces fitted together, hence are also called two-piece capsules . There was a time when two -piece capsules could be filled only with dry powders; but over the time, the manufacturers began filling capsules with pellets, granules, pastes, and liquids. Since hard capsules can be filled with substances in a variety of forms, they are believed to be more versatile than soft gels. The material types which can be filled into hard gelatin capsules are: 1)Dry Solids: Powders, pellets, granules, or tablets. 2)Semi-Solids: Suspensions or pastes. 3)Liquids: Non-aqueous liquids.   7/8/2023 PROF N.B.DESHMUKH 7

8. Size of Capsules Hard gelatin capsules are available in various sizes, designated by numbers from 000 to 5. Relative sizes of hard gelatin capsules are shown in the table . The exact capacity of any capsule varies according to the density and compressibility of the formulation. Relative amounts of water, aspirin, and sodium bicarbonate which can be filled in capsules of different sizes are compared in 7/8/2023 PROF N.B.DESHMUKH 8

9. Size of Capsules Capsule Size Water Volume (in ml) Approximate Weight (mg) Aspirin Sodium Bicarbonate 000 1.37 1000 1430 00 0.95 650 975 0.68 500 715 1 0.50 320 510 2 0.37 250 390 3 0.30 200 325 4 0.21 150 260 5 0.13 100 130 7/8/2023 PROF N.B.DESHMUKH 9

10. For small scale preparation, manual filling machines are available in the capacities of 24, 36, 96, 100, and 144 capsules, e.g., hand-operated capsule filling machine. The sizes of hard gelatin capsules intended for human consumption are shown in 7/8/2023 PROF N.B.DESHMUKH 10

11. Formulation of Gelatin Shell Gelatin shell contains: *Gelatin (main ingredient) * Plasticizers *Opacifying agents *Coloring agents *Flavouring agents *Sweetening agents *Preservatives *Water and Acids. 7/8/2023 PROF N.B.DESHMUKH 11

12. Gelatin: Gelatin is a heterogenous product derived by irreversible hydrolytic extraction of treated animal collagen. Properties of gelatin depend on: *Parent collagen, *Method of extraction, *pH value, *Thermal degradation, *Electrolyte content Sources of Gelatin: *Animal bones, *Frozen pork skin, *Hide portion 7/8/2023 PROF N.B.DESHMUKH 12

13. . . Types of Gelatin: Type A: It is derived from acid treated precursor. This type of gelatin possesses an isoelectric point in region of pH 9.0. Type B: it is derived from an alkali treated precursor of bones. This type of gelatin possesses an isoelectric point in the region of pH 4.7. Plasticizers: It increases the plasticity of the film. E.g. glycerine , sorbitol, propylene glycol Colouring Agents: These are used to impart colour to body and cap. E.g. water soluble dyes, certified lakes and vegetable colours . They are used either alone or in combination. Opacifying agents: These are used to give opacity to the gelatin film. E.g. Titanium dioxide. Flavouring agents: These are used in a concentration not more than 2%. E.g. ethyl vanillin, essential oils. Sweetining agents: E.g. Sugar not more than 5%. Preservatives: E.g. methyl paraben , potassium bisulphite . 7/8/2023 PROF N.B.DESHMUKH 13

14. Formulation of Capsule Content Glidants : e.g. talc, magnesium stearate, colloidal silica. Fillers (diluents): e.g. lactose, starch, dicalcium phosphate. Disintegrants : e.g. crosspovidone , crosscarmalose sodium. Surfactants: e.g. sodium lauryl sulphate , sodium socusta . Hydrophilic agents: e.g. methyl cellulose, hydroxyl ethyl cellulose 7/8/2023 PROF N.B.DESHMUKH 14

15. Manufacturing of Hard Gelatin Capsule Shell *Dipping: *Rotation *Drying: *Stripping *Trimming *Joining: *Sorting: *Printing: 7/8/2023 PROF N.B.DESHMUKH 15

16. Filling of Hard Gelatin Capsules Rectification: The empty capsules are oriented so that all point to the same direction, that is, body end downward. In general, the capsules pass one at a time through a channel just wide enough to provide a frictional grip at the cap end. Separation of caps from bodies: This process also depends on the difference in diameters between cap and body portions. Dosing of fill material: Various methods are employed, which are described below. Filling (dosing of material) can be done by: Auger fill principle (Gravitational forces) Vibratory fill principle (Overfill/Scrape-off excess) Piston tamp principle (Pressured measured): Again there are two types of fillers: Dosator machine, and Dosing disc machine. 7/8/2023 PROF N.B.DESHMUKH 16

17. Replacement of caps and ejection of filled capsules: The cap and body bushing portions are rejoined. Pins are used to push the filled bodies up into the caps for closure, and to push the closed capsules out of the bushings. Compressed air also may be used to eject the capsules 7/8/2023 PROF N.B.DESHMUKH 17

18. Hand-Operated, Semi-Automatic, and Automatic Equipments The machines for capsule manufacturing may be hand -operated, semi -automatic, or automatic. The various machines used in manufacturing of hard gelatin capsules are Hand-Operated Capsule Filling Equipment: It consists of ( figure 4.5 ): A bed having 200-300 holes, A loading tray having 200-300 holes, A powder tray, A pin plate having 200-300 pins, A sealing plate having a rubber top, A lever, and A cam handle. 7/8/2023 PROF N.B.DESHMUKH 18

19. Cam handle Pin plate 7/8/2023 PROF N.B.DESHMUKH 19

20. The operating steps are : *The empty capsules are filled in the loading tray and placed over the bed. *The cam handle is operated to separate the capsule caps from their bodies. * The powder tray is placed in a proper position and filled with an accurate quantity of powder with scraper. * The excess of powder is collected on the platform of the powder tray. * The pin plate is lowered and the filled powder is pressed by moving the pin downwards. * After pressing, the pin plate is raised and the remaining powder is filled into the capsule bodies. * The plate with the rubber top is lowered and the lever is operated to lock the caps and bodies. * The loading tray is then removed and the filled capsules are collected.   * With a 200 hole machine, about 5000 capsules can be filled in one hour, whereas, in a machine having about 300 holes, about 7500 capsules can be filled in one hour . 7/8/2023 PROF N.B.DESHMUKH 20

21. Semi-Automatic Capsule Filling Equipment : *The capsules are transferred to the perforated capsule filling ring which is rotated on a turntable. *While rotating the ring is subjected to vacuum which pulls the bodies into the lower half of the ring, leaving the caps in the upper half. *The upper and lower halves of the capsule filling ring are separated manually. *This hopper contains a drill mechanism which is utilised to feed the powder into the capsule bodies. *The capsule cap is detached and the empty capsule body is held between the thumb and forefinger and frequently pressed downward until it is fully filled. *The cap is th en replaced and the filled capsule is weighed using an empty capsule of the same size as a tare. *After the filling of capsule bodies, the cap and body rings are joined together. 7/8/2023 PROF N.B.DESHMUKH 21

22. Empty Capsule Separation of Capsule Powder Filling Capsule Closing Finished Capsule 7/8/2023 PROF N.B.DESHMUKH 22

23. Automatic Capsule Filling Equipment Machines developed for industrial use 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 1,65,000 capsules per hour The automatic capsule filling process normally involves four simple steps : Removal of caps, Filling of the bodies, Replacement of caps, and Ejection of filled capsules 7/8/2023 PROF N.B.DESHMUKH 23

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25. Special Techniques of Formulation of Hard Gelatin Capsules Imprinting on capsule s provides info rmation about the company and enables product identification. Special purpose capsules are given a special treatment to decrease the ir solubility. This may cause delayed absorption of the active ingredient , facilitating enteric properties . 7/8/2023 PROF N.B.DESHMUKH 25

26. Manufacturing Defects Deliquescent or Hygroscopic Powde rs : A gelatin capsule contains water which is extracted or taken up by a hygroscopic drug. This renders the capsule brittle, which leads to its cracking. Addition of an absorbent (like magnesium carbonate, heavy or light magnesium oxide ) overcomes this dif ficulty , provided the capsules are packed in tightly closed glass capsule vials 7/8/2023 PROF N.B.DESHMUKH 26

27. Eutectic Mixtures: Certain substances when mixed together tend to liquefy or form a pasty mass due to the formation of a mixture having a melting point lower than the room temperature. Addition of Inert Powders : When quantity of the drug to be filled in capsules is very small, an inert substance or a diluent is added to increase th e powder bulk, thus, facilitating easy filling of capsules. Use of Two Capsules : Some manufacturers separate incompatible ingredients of the formulation by placing one of the ingredients in smaller capsule, and then placing this smaller capsule in a larger capsule containing the other ingredients of the formulation 7/8/2023 PROF N.B.DESHMUKH 27

28. *Filling of Granular Powder : Powders lacking adhesiveness and most of the granular powders are difficult to fill in the capsules by punch method. This is because they are not compressible and flow out of the capsule as soon as they are lifted from the powder pile into which they are punched. To overcome this difficulty the non-adhesive powders should be moistened with alcohol and the granular powders should be reduced to powder before filling into capsules. *Improper Flow of the Powder Mixture during the Filling Operation: Addition of suitable quantities of glidants or lubricants is helpful in improving the flow properties of the powder mixture. *Segregation and Homogeneity: Generally, semi -automatic or automatic machines performing capsule filling operation may face this error. The segregation and inhomogeneity of the particles may occur as a result of vibrations generated by these heavy-duty machines. Utilisation of powder having 7/8/2023 PROF N.B.DESHMUKH 28

29. Manufacturing Defects Incompatibility: This defect may occur as a result of incompatibility among formulation ingredients, formulation components, and the capsule shell. A thorough understanding of physical and chemical properties of each ingredient is needed to prevent such defects. The excipients generally used in the filling of hard gelatin capsules are: Diluents: Lactose, corn starch, and microcrystalline cellulose are the diluents used to increase the powder bulk and thus to facilitate its easy and accurate handling during filling operations. Disintegrants : Corn starch, microcrystalline cellulose, sodium starch glycolate , and croscarmellose are the disintegrants used for breaking down the powder bulk exposed to a liquid medium. Glidants : Colloidal silicon and talc are the glidants used to improve the powder flow by reducing the inter-particle attraction and preventing agglomeration. Lubricants: Magnesium and other metallic stearates are the lubricants used to minimise the contact between powder particles and components of the filling machine. Surfactants: Sodium lauryl sulphate is employed into the powder mixture to reduce the surface tension and promote powder wetting with the discharge medium containing greater quantities of hydrophobic constituents 7/8/2023 PROF N.B.DESHMUKH 29

30. In-Process and Final Product Quality Control Tests 1) Appearance, 2) Size and shape, 3) Unique identification markings, 4) Assay, 5) Content of active ingredients, 6) Content uniformity test, 7) Uniformity of mass, 8) Mass variation test, 9) Disintegration test, 10) Dissolution test, and 11) Moisture permeation test.   7/8/2023 PROF N.B.DESHMUKH 30

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