Unit 3 capsules industrial Pharmacy.pptx

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1. 2/25/2022 Department of Pharmaceutics 1

2. INTRODUC T ION: CAPSULES: The term capsule is derived from the Latin word capsula, meaning a small container. Capsules are defined as solid unit dosage forms enclos ing accurately measured quantity of medicaments in a water soluble shell made up of gelatin. Depending on the composition of gelatin, capsules are available in two types-hard gelatin capsules which are intended for the capsulation of particulate solids ( such as powders, granules, and pellets) and soft gelatin capsules which encloses the medicaments in the form of powders, pastes, or non-aqueous liquids. 2/25/2022 Department of Pharmaceutics 2

3. ADVANTAGES OF CAPSULES: Capsules are easy to swallow because of their slippery texture . They efficiently mask the unpleasant taste of certain drugs which cannot be achieved in case of tablets or liquid oral formulations. There are attractive in appearance. They can be filled quickly and conveniently. They are economical. They are easy to handle and carry. . 2/25/2022 Department of Pharmaceutics 3

4. The ready solubility of gelatin at gastric pH provides rapid release of medication in the stomach. Packaged and shipped by manufacturers at lower cost less breakage than liquid forms 2/25/2022 Department of Pharmaceutics 4

5. DISADVANTAGES OF CAPSULES: Capsules are not suitable for liquids that dissolve gelatin, such as aqueous or hydro alcoholic solutions. The concentrated solutions which require previous dilution are unsuitable for capsules because if administered as such lead to irritation into stomach. Capsules are not suitable for enclosing highly acidic or alkaline drugs because acidic drugs cause hydrolysis of gelatin, whereas alkaline drugs cause tanning effect which reduces the solubility of the gelatin shell 2/25/2022 Department of Pharmaceutics 5

6. Hygroscopic ingredients cannot be capsulated as they absorb water from the shell and make it brittle. Efflorescent substances cannot be capsulated as they make the shell moist by releasing moisture. 2/25/2022 Department of Pharmaceutics 6

7. *The largest size of the capsule is No: 000. *The smallest size is No: 5. *The standard shape of capsules is traditional, symmetrical bullet shape. 5 SHAPES OF CAPSULE: 2/25/2022 Department of Pharmaceutics 7

8. Formulation of hard gelatin capsule shell: Gelatin, water, colorants, opacifying agents, Preservatives: Flavours, Sugars Solvents Thickening agents 2/25/2022 Department of Pharmaceutics 8

9. GELATIN: Gelatin is a heterogeneous protein obtained by irreversible hydrolysis of animal collagen processed from bones, white connective tissue, skin trimmings and frozen pork skin. Gelatin is a regarded as the best suitable ingredient for the manufacture of capsule shell owning to its unique physical, chemical and physiological properties. 9 2/25/2022 Department of Pharmaceutics 9

10. These properties depend on the collagen source, methods of extraction, ph value, thermal degradation and electrolyte content. commercially it is available as fine or coarse powder, flakes and sheets. It has unique solubility characteristics, being soluble in hot water and in warm gastric fluids but insoluble in cold water. However it softens upon absorbing 10 times its weight of water, a property which facilitates the disintegration of capsules in the stomach upon ingestion. 2/25/2022 Department of Pharmaceutics 10

11. TYPES OF GELATIN: There are two basic types of gelatin Type - A Type - B TYPE - A It is obtained by acid hydrolysis of pork skin and exhibits an iso electric point at pH-9. type A gelatin contributes plasticity and clarity to the gelatin blend therefore reduces the cloudiness in the finished capsules. 2/25/2022 Department of Pharmaceutics 11

12. TYPE - B This grade of gelatin is obtained by acid and alkaline treatment of animal bones and hide portions. exhibits an iso electric point at pH-4.7. 2/25/2022 Department of Pharmaceutics 12

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14. PROPERTIES OF GELATIN: Bloom strength: physical stability and strength of the capsule shell is directly proportional to the bloom strength . Bloom strength is defined as the measure of cohesive strength of cross linking b/w the gelatin molecules. Bloom strength is determined by measuring the weight in grams required to penetrate a plastic plunger of 0.5 inches in diameter 4 mm deep into 6.66% w/w gelatin gel maintained at 10 degree centigrade. 13 2/25/2022 Department of Pharmaceutics 14

15. Bloom strength Bloom strength ranges from 150-250 gms . 2/25/2022 Department of Pharmaceutics 15

16. 3. Viscosity; In general the higher the bloom, the greater the viscosity. Viscosity is determined by measuring the flow time of a 6.67% solution of gelatin through a U-tube viscometer at 60 °C. Viscosity measurement is given in millipoise units and varies between 2 5 and 4 0mps. 14 2/25/2022 Department of Pharmaceutics 16

17. Foamability; In general pigskin grades tend to have better foaming properties. Gel a tin l o wers the surface t e nsio n , all o wing for t he inc o rp o rati o n o f ai r , and sta b ilizes the f o am o n ce aerated. 2/25/2022 Department of Pharmaceutics 17

18. Color and odor; The gelatin should be as clear as possible in solution. Clarity is measured using a turbidimeter . The gelatin should be without odor. 15 2/25/2022 Department of Pharmaceutics 18

19. Plasticizers: these are added to the gelatin mass to confer softness, hardness, elasticity and thickness to the capsule shell. The amount of plasticizer to be added depends upon the type of capsule (hard or soft) and storage conditions. Eg : glycerin, sorbitol, propylene glycol 2/25/2022 Department of Pharmaceutics 19

20. Water : Water is essential component in preparation in gelatin mass. Similar to the plasticizer , the amount of water to be added depends on the type of capsule and storage conditions. Soft gelatin capsule shells contain more water and plasticizer than hard gelatin capsule. 2/25/2022 Department of Pharmaceutics 20

21. Colorants: Capsule shells may be clear and colourless , but to improve their elegance and to make them distinctive and consumer appealing, certain FD&C and D&C approved dyes, pigments are added to the gelatin mass. 2/25/2022 Department of Pharmaceutics 21

22. Opacifying agents: These are used to minimize the transparency and to make the capsule shell opaque. Opacified capsule shells prevent the degradation of photosensitive fill materials. Eg : titanium dioxide 2/25/2022 Department of Pharmaceutics 22

23. Presevatives : Since gelatin contains water, preservatives are added to retard the growth of microbes and to maintain the stability of the shells for a long period Eg : methyl paraben, propyl paraben. Flavours : these are added to impart good flavour to the capsule shell. Sugars: these are used in chewable gelatin capsules to impart sweet taste and to mask objectionable taste. 2/25/2022 Department of Pharmaceutics 23

24. Solvents: These are added to impart elegance and palatability to the capsule shells. Eg : oils Thickening agents: Since viscosity of the gelatin is an important aspect of the its quality therefore certain thickening agents are added to adjust the desired viscosity. Eg : methyl cellulose. 2/25/2022 Department of Pharmaceutics 24

25. FORMULATION OF HARD GELATIN CAPSULE FILL MATERIAL A. SLECTION OF INGREDIENTS: IN ADDITION TO THE ACTIVE INGREDIENTS, CAPSULE FORMULATION REQUIRE THE USE OF ADDITIONAL NON-ACTIVE INGREDIENTS CALLED EXCEPIENTS TO PRODUCE A CAPSULATED BLEND. IDEAL PROPERTIES OF ADDITIVES: THEY SHOULD NOT ALTER THE THERAPEUTIC ACTIVITY OF THE DRUG. THEY SHOULD NOT REACT WITH OTHER ADDITIVES OF THE PREPARATION. THEY SHOULD BE STABLE THROUGHT OUT THE SHELF LIFE OF THE PRODUCT. THEY SHOULD BE OF GOOD QUALITY AND SHOULD NOT IMPART ANY IMPURITIES TO THE DOSGEFORM. 2/25/2022 Department of Pharmaceutics 25

26. FORMULATION OF CAPSULE FILL MATERIAL DILUENTS: THESE ARE ALSO CALLED AS FILLERS. WHEN THE DOSE OF PARTICULAR DRUG SUBSTANCE IS TOO SMALL TO COMPLETELY FILL THE SMALLEST CAPSULE SHELL, DILUENTS ARE ADDED TO PRODUCE THE PROPER CAPSULE FILL VOLUME. EG: LACTOSE, MANNITOL, MCC, STARCH DISINTEGRANTS:THEY PROMOTE THE BREAKUP AND DISTRIBUTION OF THE CAPSULE CONTENTS IN THE STOMACH. HENCE HELP IN EVOKING FASTER THERAPEUTIC EFFECT. 2/25/2022 Department of Pharmaceutics 26

27. FORMULATION OF CAPSULE FILL MATERIAL GLIDANTS/ LUBRICANTS: THEY ENHANCE THE FLOW PROPERTIES OF THE CAPSULE FILL BY ALLOWING STEADY PASSAGE FROM THE HOPPER THROUGH THE AUTOMATED EUIPMENT INTO THE CAPSULE SHELLS. EG: CALCIUM STEARATE, MG.STEARATE, AND TALC ETC SURFACTANTS: THESE AGENTS FACILLITATES THE WETTING OF DRY PARTICLES BY THE GI FLUIDS BY MINIMIZING THE WATER PROOFING PROPERTIES OF CERTAIN WATER INSOLUBLE AGENTS FILLED IN THE CAPSULE. EG: SLS, 2/25/2022 Department of Pharmaceutics 27

28. ANTIDUSTING AGENTS: DUST IS CONSIDERED TO BE THE MAJOR PROBLEM IN LARGE SCALE CAPSULE FILLING OPERATIONS. DUST FROM POWDER MIX CONTAING POTENT DRUGS IF INHALED BY THE OPERATORS MAY LEAD TO SEVERE HEALTH COMPLICATIONS. TO PREVNT THIS SOME ANTIDUSTING AGENTS ARE MIXED. 2/25/2022 Department of Pharmaceutics 28

29. B. PRPEARATION OF FORMULATION: THERAPEUTICALLY ACTIVE CONSTITUENTS ARE THOROUGHLY MIXED WITH SUITABLE ADDITIVES. THE UNIFORM MIXTURE SO OBTAINED IS FILLED INTO THE CAPSULE SHELLS. DRUGS IN LOW DOSES ARE TO BE STRICTLY MONITORED WHILE BLENDING FOR UNIFORMITY, THE LACK OF WHICH MAY ALTER THE DRUG DISTRIBUTION THUS AFFECTING THE DESIRED THERAPEUTIC EFFICACY. FOR FILLING OF POWDERED DRUD IN THE CAPSULE SHELL THE DENSITY AND PARTICLE SIZE OF BOTH THE DRUG AND ADDITIVES SHOULD BE ALIKE FOR UNIFORM MIXING. 2/25/2022 Department of Pharmaceutics 29

30. PELLETS: DRUGS SUBTSNCES WHICH ARE DESIGNED FOR MODIFIED RELEASE ARE MADE INTO PELLETS AND COATED WITH SUITABLE COATING AGENTS. THESE COATED PELLETS ARE THEN FILLED IN THE EMPTY CAPSULE SHELL. 2/25/2022 Department of Pharmaceutics 30

31. TYPES OF CAPSULES: Capsules are available in two types: 1.Hard gelatin capsules 2.Soft gelatin capsules. 1.Hard gelatin capsule 2.Soft gelatin capsule 2/25/2022 Department of Pharmaceutics 31

32. HARD GELATIN CAPSULES: The hard gelatin capsule consists of two pieces in the form of cylinders closed at one end. The shorter piece is called the cap. This cap fits over the open end of longer piece called body. Hard gelatin capsules are also known as dry-filled capsules or two piece capsules. The drug substance placed in the body and the caps are slided over it, hence enclosing the drug substance. 2/25/2022 Department of Pharmaceutics 32

33. PRODUCTION OF EMPTY CAPSULE SHELLS capsule shells are manufactured by fully automatic machines holding about 500 pins or pegs. made up of stainless steel to produce shells of desired shape and size. both caps and bodies are prepared simultaneously. such machines have mechanisms for dipping, spinning, drying, trimming, stripping and joining of caps and bodies. 2/25/2022 Department of Pharmaceutics 33

34. Manufacturing of Hard gelatin capsules Steps involved in making empty gelatin capsules… 1.Dipping 2.Spinning 3.Drying 4.St r i p p i ng 5.Trimming and Joining 6.Polishing 18 2/25/2022 Department of Pharmaceutics 34

35. 1.DIPPING: Pairs of the stainless steel pins are dipped into the dipping solution (Gelatin solution) to simultaneously form the caps and bodies. The dipping solution is maintained at a temperature of about 500C in a heated, jacketed dipping pan. SPINNING: The pins dis t rib u te the are r o tat e d to g e l at i n ov e r the pins uniformly. 2/25/2022 Department of Pharmaceutics 35

36. 3.DRYING : The gelatin is dried by a blast of cool air to form a hard shells. The pins are moved through a series of air drying kilns to remove water STRIPPING : A series o f br o n z e jaws strip t he cap and body portions of the capsules from the pins. 20 2/25/2022 Department of Pharmaceutics 36

37. 5.TRIMMING AND JOINING: The stripped cap and body portions are trimmed to the required length by stationary knives. The cap and body lengths are precisely trimmed to a ±0.15 mm tolerance. After trimming to the right length, the cap and body portion are joined. Finished capsules are pushed onto a conveyer belt which carries them out to a container. 21 2/25/2022 Department of Pharmaceutics 37

38. Perf e ct ca p sules are imprinted with the clie n t logo on high-speed. Capsule quality is monitored throughout the production process including size, moisture content, single wall thickness, and color. Capsules are sorted and visually inspected on specially designed Inspection Stations. 2/25/2022 Department of Pharmaceutics 38

39. 22 2/25/2022 Department of Pharmaceutics 39

40. : Acela-cota pan is used to dust POLISHING : Pan Polishing and polish. Cloth Dusting : Capsule are rubbed with cloth. Brushing : Capsule are feed under soft rotating brush . Fig : Capsule polishing machine 23 2/25/2022 Department of Pharmaceutics 40

41. Capsule size selection: for human use empty gelatin capsule shells are available in eight different sizes varying in their length, diameter, and capacities. The size ranges from 000(largest) to 5(smallest) and are used to capsulate 65 mg to 1g of powdered material. Depending upon the nature of powdered drug, 65mg may be placed in capsule size 5 and 1g in 000. for veterinary purpose larger sizes of capsule sizes of numbers 10, 11, and 12 are also available which approximately contain 7.5, 15, and 30 g of the drug substance. 2/25/2022 Department of Pharmaceutics 41

42. FILLING OF HARD GELATIN CAPSULES : Hand Operated methods or Semi Automatic Capsules Devices. Punch Method or Manual Filling. Automatic filling machine. ex: osaka capsule filling machine ,macofar capsule filling machine HAND OPE 2/25/2022 Department of Pharmaceutics 42

43. op It consists of: 1.A bed having 200-300 holes 2.A loading tray having 200-30 holes 3.A powder tray 4.A pin plate having a rubber t 5.A lever 6. A cam handle. 2/25/2022 Department of Pharmaceutics 43

44. The empty capsules are filled in the loading tray . ↓ and it is 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 plat for of the powder tray ↓ The pin plate is lowered and the filled powder is pressed b 27 y moving 2/25/2022 Department of Pharmaceutics 44

45. After pressing ,the pin plate is raised and the remaining powder is filled into the bodies of the capsules ↓ The powdered tray is removed after its complete filling ↓ The cap holding tray is again placed in position ↓ The plate with the rubber top is lowered and the lever is operated to lock the caps a ↓ The loading tray is then remo and the filled capsules are co nd bodies ved llected 28 2/25/2022 Department of Pharmaceutics 45

46. PUNCH METHOD: Powder is placed on a sheet of a clean paper or porcelain plate using spatula which is formed into a cake having a depth of approximately one-fourth to one-third the length of the capsule body. Then empty capsule body is held between the thumb and forefinger and punched vertically into the powder cake repeatedly until filled. 29 2/25/2022 Department of Pharmaceutics 46

47. FILLING OF HARD CAPSULE SHELL The process of working: Rectification Separating the caps from empty capsules Filling the bodies Replacing the caps Sealing the capsules Cleaning the outside of the filled ca 160,000 capsules per 8hour shift 2/25/2022 Department of Pharmaceutics 47

48. Rectification ; The empty hard gelatin capsules are fed from the storage hopper into the rectifying unit which aligns the capsules with their caps turned up and bodies down. 31 2/25/2022 Department of Pharmaceutics 48

49. Separation of caps from body ; From the rectifying unit the capsules are fed into the rotating ring . The ring consists of two parts the upper ring and lower ring with cavities for holding the capsules shells. Vaccum is applied from the underside of the lower ring which causes the capsule bodies to sit into the lower ring leaving the cap in the upper ring. 32 2/25/2022 Department of Pharmaceutics 49

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52. Principles of capsule Filling: Auger Fill principle: empty capsules – rectifying unit Rectifier descends the capsules such that caps are turned up and bodies down. From rectifying unit these are placed one by one in filling ring kept on rotating mode. The lower ring is rotated with a suitable speed and the hopper containing powdered drug is held over this ring. The auger drives the drug into bodies. 33 2/25/2022 Department of Pharmaceutics 52

53. Vibratory Fill Principle: The feed is placed in the feed hopper and the capsule bodies are passed under it. A perforated resin plate is placed in the feed hopper. Due the vibrations of the resin plate, the powder flows freely through the pores into bodies. 2/25/2022 Department of Pharmaceutics 53

54. Piston – Tamp principle : These piston tamps alter the shape of powder by compressing the powder to form slugs. These plugs are transferred into the empty capsule bodies with the application of slight pressure. Finally the bodies are ejected from the machine. Compression force 50-200N a)Dosator machine b) Dosing Disc 2/25/2022 Department of Pharmaceutics 54

55. Vacuum Fill principle: It consists of an open ended cylinder. The upper end of this is fitted with a piston. The open end is placed in bulk powder. Vacuum is applied & the piston is moved upward by sucking the predetermined amount of powder which results in filling 2/25/2022 Department of Pharmaceutics 55

56. HOFLIGER KARG AUTOMATIC CAPSULE FILLING MACHINE 35 ZANASI AUTOMATIC CAPSULE FILLING MACHINE 2/25/2022 Department of Pharmaceutics

57. Various Filling Machine Available… Eli-lily Farmatic Hofliger and Karg Zanasi Nigris Parke-Davis Osaka Macofar SAS (These machine differ in there design and output ) 36 2/25/2022 Department of Pharmaceutics

58. SEALING, POLISHING, SORTING, AND CAPSULE IMPRINTING The capsules filled by manual or hand filling machines are sealed in order to prevent the detachment of caps from the bodies during packaging, handling or storage. Different manufacturers adopt different sealing techniques. 1.Banding: in this method capsules are sealed by Placing g e latin color b a nds at the meeti n g point of caps and the bodies. 2/25/2022 Department of Pharmaceutics 58

59. Locking and Sealing of Capsules : Moistening – in this method , inner surface of caps is moistened with warm gelatin solution and these are then quickly slipped over the filled bodies. Spot Welding – capsules are sealed by welding process. which causes the cap and body to fuse. the joints which leaves a ring like appearance at the point of sealing 37 2/25/2022 Department of Pharmaceutics 59

60. Thermal welding – In this method, Applying wetting sol. At the meeting points of cap and body which causes lowering of M.P at applied area. Finally they are sealed at a temp. 40-45ºc. 2/25/2022 Department of Pharmaceutics 60

61. P olishing : Polishing : before final packaging the filled and sealed capsules are subjected to dusting and polishing to remove any adhering particles and to make them glossy. Cloth dusting: it is a manual method in this small number of capsules are rubbed with a cloth. Pan polishing: accela - cota tablet coating pans may be used for polishing the filled capsules. These pans are lined with cheese cloth or polyurethane which captures the dust and other powders adhering to the capsules. 38 2/25/2022 Department of Pharmaceutics 61

62. Sorting: this operation is used to remove the imperfect and damaged capsules. On a small scale this can be done visually however on large scale this is done by automated electronic sorting devices. Imprinting: usually capsules are printed with company name and logo or product identification. They are printed before filling. 39 2/25/2022 Department of Pharmaceutics 62

63. SOFT GELATIN CAPSULE: Definition:- Soft Gelatin capsules are also known as soft elastic capsules or soft gels. The composition of soft gelatin capsules is similar to the hard gelatin capsules shells, the only diff, being the high conc. Of water and plasticizer. soft gelatin shells containing a liquid, a suspension, or a semisolid. Soft gelatin is mainly composed of gelatin, plasticizers, preservative, colouring and opacifying agents, flavoring agents and sugars. 2/25/2022 Department of Pharmaceutics 63

64. ADVANTAGES OF SOFT GELATIN CAPSULES: Easy to administer. Easy to manufacture. Liquids can be encapsulated Small to large sizes possible. Elegance. Bioavailability of drugs is improved since they are present in liquid form. Odour and taste masking. Can be used for ophthalmic preparations. e.g. aplicaps, vaginal/ rectal suppositories. 41 2/25/2022 Department of Pharmaceutics 64

65. SHAPE OF C A PSULE: The shape of soft gelatin capsule are round, oval, oblong, tube. 42 2/25/2022 Department of Pharmaceutics 65

66. soft gelatin capsules composition: A typical gel mass formula for making soft gelatin capsules would be: Gelatin 35-45% Plasticizer 15-25% (glycerin or sorbitol) Water ~40% Dye / Pigment as needed Opacifier as needed Other (flavour, sugar,) as needed 43 2/25/2022 Department of Pharmaceutics 66

67. Formulation : Formulation for soft gelatin capsules involves liquid, rather than powder technology. Materials are gen e rally fo r mulated to prod u ce t h e smallest p o ssib l e ca p su l e co n siste n t with m a x im um s ta b ilit y , therapeutic effectiveness and manufacture efficiency. The liquids are limited to those that do not have an adverse effect on gelatin walls . 44 2/25/2022 Department of Pharmaceutics 67

68. Vehicles used in soft gelatin capsules: Two main groups : likely m o r e 1. W at e r im miscible, vola t ile or more volatile liquids such as vegetable oils, mineral oils, medium-chain triglycerides and acetylated glycerin . 2 . W ater m i scible, no n v o latile liquids such as low molecular weight PEG have come in to use more recently b e ca u s e of th e ir a b ility to mix with wat e r rea d ily and accelerate dissolution of dissolved or suspended drugs. All liquids used for filling must flow by gravity at a 45 2/25/2022 Department of Pharmaceutics 68

69. Manufacturing of soft gelatin capsules: Plate process Rotary die process Reciprocating die process 46 2/25/2022 Department of Pharmaceutics

70. Plate process The molten glycogelatin preparation is placed on a plate containing hollow elliptical or hemispherical dies. Over this a measured amount of anhydrous liquid containing medicaments is evenly poured which is then carefully covered with a second sheet of gelatin. The sandwich is then compressed b/w the two plates by applying mechanical pressure. The pressure forces glycogelatin sheet and fill material into the dies resulting in simultaneous formation, filling and sealing of capsules. 2/25/2022 Department of Pharmaceutics 70

71. 2.ROTARY DIE PROCESS: This process developed by Robert P.Scherer in 1933, is the most widely used method for the prepration of soft gelatin capsules. The rotary die machine consisting of one pair of contra rotating cylinders with dies set in them. Previously molted gelatin flowing under gravity from a tank is fed to a metering device which controls the flow of gelatin onto the cylinder and forms two continuous ribbons . The ribbons are fed through a mineral oil lubricating bath over guide rolls and then down b/w the wedges and rotating cylinders. At the moment 48 2/25/2022 Department of Pharmaceutics 71

72. When the opposite dies converge and form pockets of gelatin ribbon, a metered fill of drug flowing under gravity through the leads and wedge is injected b/w the die rolls by a metered fill pump. The capsule at this moment is half sealed when the pressure of the pumped materials forces the gelatin into the die pockets. Simultaneously, these pockets of gelatin containing the fill material are sealed by the mechanical pressure on the die rolls and heat by the wedge. The capsules are shaped and cut from the ribbon. 2/25/2022 Department of Pharmaceutics 72

73. Figure 3.8 Schematic drawing of a rotary-die soft gelatin capsule filler (R.P. Scherer: Detroit, MI). 49 2/25/2022 Department of Pharmaceutics 73

74. 3.Reciprocating die process This process is similar to rotary die process, the only diff” being that the gelatin ribbons are fed b/w a pair of vertical dies that continuously open and close to form rows of pockets in the gelatin ribbons. These pockets are filled with the fill material are sealed, shaped and cut off from the ribbon as they move through the machine. 2/25/2022 Department of Pharmaceutics 74

75. Packing and storage Capsules may be packaged in suitably designed unit dose containers made up of glass or plastic or as single unit dose in blister packs or aluminum strip packs. Storage: hard gelatin capsules have moisture content b/w 12-15%. When stored at high humidity, they absorb moisture and soften resulting in the loss of shape. Under low humidity conditions, they lose water from the shell and become brittle. So, ambient temp.. And humidity levels are required 2/25/2022 Department of Pharmaceutics 75

76. Minimum- 35% RH, 15C Best possible- 50%RH, 20C Maximum- 65% RH, 25C Soft gelatin capsules should be stored in air conditioned area wherein the humidity does not exceed 45% RH at 21-24C. 2/25/2022 Department of Pharmaceutics 76

77. EVALUATION OF CAPSULES: Content uniformity test Moisture permeation test Weight variation test Dissolution test Disintegration test 56 2/25/2022 Department of Pharmaceutics 77

78. Content uniformity test 30 Capsules are selected and 10 of these are assayed individually by the specified procedure to determine the percentage purity of the active ingredient . At least 9 of these contain 85-115% of drug and none contain below 75-125% of drug. If 1 to 3 of them fall outside of 85 -115% limits , the remaining 20 capsules are individually assayed and the net result of the 30 capsules assayed should prove that not less than 27 of the 30 capsules are within the 85-115% and no capsule is beyond the stated potency range of 75-125%. 2/25/2022 Department of Pharmaceutics 78

79. Moisture penetration test USP demands the determination of degree and rate of moisture penetration by single unit and unit-dose containers to assure their suitability for packaging capsules. Accordingly moisture penetration test is carried out by packaging the capsule together with a colour revealing desiccant pellet and exposing to known RH for a specific time period. Any change in colour of pellet reveals absorption of moisture. The weight of test dosage form is then compared with its weight before test. 2/25/2022 Department of Pharmaceutics 79

80. Weight variation test: 20 capsules are taken at random and weighed. Their average weight is calculated, then each capsule is weighed individually and their weight is noted. The capsule passes the test if the weight of individual capsule falls with in 90- 110% of the average weight. (percentage deviation is ±10%).If the variation exceeds ±10%, then determine the actual weight of the medicament separately and compare it with the average weight. 2/25/2022 Department of Pharmaceutics 80

81. Dissolution Test: Place 10 m l of water f ree f rom dis solved air having temperature of 36.5ºC to 37.5ºC Place specified number of capsules in each basket. St a rt mo t or and a djust s p eed 1 00 rpm as per monograph. Withdraw the req u ired vo l ume of solu t i o n af t er 45 minutes or as specified in the monograph. Filter and weigh the amount f active ingredients by the method specified in the monograph. The test i s said to p a ss i f t he amo u n t of acti v e in g re d ient i s not less th a n 7 % of the s ta t ed amo u nt 59 given in the monograph. 2/25/2022 Department of Pharmaceutics 81

82. Disintegration Test: Place one capsule in each basket. Set the temperature of water to 37 +/- 2 Use disc if HGC floats whereas for soft gelatin use the disc. Operate the apparatus for 30 mins for HGC and 60 minutes for SGC. The test is said to pass if no residue is left on the screen of the apparatus. Repeat the test for 12 capsules if more than 1 or 2 capsules fails to disintegrate The test passes if 16 out of 18 capsules disintegrate or else fail. 60 2/25/2022 Department of Pharmaceutics

83. Diff”b /w hard and soft gelatin capsules Hard gelatin capsule Soft gelatin capsule Consisting of two detachable parts, body and cap It turns into a single unit after sealing Shape of the capsule is cylindrical Shape of the capsule may be oval, round, or tube like Mainly used for capsulating solid medicaments Liquid medicaments, may be oils, suspensions, ophthalmic products The size of capsule varies from 000 to 5 The capacity of capsule varies from 0.1 ml to 30 ml Bioavailability is relatively less as the solid medicaments have to undergo disintegration and dissolution before their absorption. Bioavailability is relatively more 2/25/2022 Department of Pharmaceutics 83

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