CAPSULES - st.pptx. by Rajan Kumar Singh, sanskar college of pharmacy and research

Capsule

1. Capsules

2. The word capsule is derived from the Latin word ‘ Capsula ’ which means a small box or container . Capsules are solid dosage forms in which one or more medicinal and or inert substances are enclosed within a small shell prepared from a suitable form of gelatin. Capsules are usually intended to be administered orally by swallowing them whole.

3. Advantages: Neat and elegant in appearance . Ease of handling and portability. Tasteless shell to mask the unpleasant taste/odor of the drug. Provide a smooth, slippery and easily swallowable capsule shell. The fill material requires no or minimum excipients . The ready solubility of gelatin at gastric pH provides rapid release of medication in the stomach.

4. Packaged and shipped by manufacturers at lower cost less breakage than liquid forms . Tightly sealed capsules shell protects the enclosed drug from environmental conditions. More stable and longer shelf life .

5. Disadvantages: Capsules are not suitable for liquids that dissolve gelatin, such as aqueous or hydro alcoholic solutions. Not useful for efflorescent or deliquescent materials. Efflorescent cause capsules to soften & Deliquescent may dry the capsule shell to brittleness.

6. Capsules are not suitable for very acidic or alkaline drugs because acidic drug may hydrolyze the gelatin wheras alkaline drugs reduce solubility of gelatin due to tanning effect. Rapid release of water soluble salts such as KCl, KBr and ammonium chloride may cause gastric irritation.

7. TYPE Types of Capsules Capsule may classified depending on nature of shell Hard Gelatin Capsules Soft Gelatin Capsules, also called as softgels The hard gelatin 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 of the longer piece, called the “body”. The soft gelatin capsule is also called as “one piece”

8. Difference between hard gelatin and soft gelatin capsules Soft gelatin capsules, also called as soft-gels are sealed hermetically as 1-piece capsules that contain a semi-solid or liquid fill, whereas hard gelatin capsules shell consists of two parts namely a body and a cap. Hard gelatin capsules are cylindrical in shape while soft gelatin capsules are available in round, oval and tube-like shapes.

9. Hard gelatin capsules are mostly used for encapsulation of solid formulations in the form of powder, beads, pellets or granules whereas soft gelatin capsules consists of liquid or solids dissolved or dispersed in suitable base but may also consists of powder and granules. The ratio of plasticize r and gelatin is more in a soft gelatin capsule (20 to 40% of weight) than in hard gelatin capsule ( upto 5 % of weight) The filling of Hard gelatin capsules is multistep operation whereas Filling and sealing of soft gelatin capsules are done in a single operation on machines. Soft gelatin shows rapid bioavailability than hard gelatin capsules.

10. HARD GELATIN CAPSULES

11. Hard Gelatin Capsules These are used for administration of solid medicaments. The capsule shell is prepared from gelatin. It consists of two parts i.e. body and cap. The powdered material is filled into the cylindrical body of the capsules and then the cap is placed over it.

12. Material for production of Capsule Shell: Constituents Examples Function Gelatin Type A, Type B Main ingredient Plasticizers Glycerin USP , glycerol (85% & 98%) Imparts s oftness, Elasticity & hardness Preservatives Methyl paraben, Sorbic acid (0.2%) Retard growth of microorganisms Solvents Oils, water Elegance Opacifying agents Tio2(0.2-1.2%) Minimize transparency Colours Veg. colours,FD&C water soluble dyes, certified lakes Gives pleasant appearance to the shells. Thickening agents Methyl cellulose Adjust viscosity of gelatin

13. Material for production of hard gelatin Capsule Shell: 1. GELATIN Gelatin is heterogeneous product derived by hydrolytic extraction of animal's collagen. The sources of gelatins including animal bones, hide portions and frozen pork skin. TYPES OF GELATIN Type A Type B

14. TYPE A - Derived from acid treated precursor that exhibits an isoelectric point at pH-9. It is manufactured mainly from pork skin . TYPE B - Derived from alkali treated precursor that exhibits an isoelectric point at pH-4.7. It is manufactured mainly from animal bones .

15. Gelatin has been the raw material of choice because of The ability of a solution to gel to form a solid at a temperature just above ambient temperate conditions, which enables a homogeneous film to be formed rapidly on a mould pin.

16. The reason for this is that gelatin possesses the following basic properties: It is non-toxic, widely used in foodstuffs and acceptable for use worldwide. It is readily soluble in biological fluids at body temperature.   It is good film-forming material , producing a strong flexible film   The gelatin films are homogeneous in structure, which gives them strength

17. Preparation of Gelatin

18. 2. Colorants – Color is used principally to identify a product in all stages of its manufacture and use. The colorants that can be used in capsules are of two types: water soluble dyes or insoluble pigments. Three most commonly used dyes are erythrosine, indigo carmine and quinolone yellow . The two types of pigments used are iron oxides- black, red and yellow and titanium dioxide which are white and used to make the capsule opaque.

19. 3. Process aids – Preservatives and surfactants are added to the gelatin solution during capsule manufacture to aid in processing. Gelatin solutions are an ideal medium for bacterial growth at temperatures below 55 ○ C . preservatives are added to the gelatin and colorant solutions to reduce the growth of microorganisms The materials used as preservatives include: sulfur dioxide which is added as the sodium salts bisulfite or metabisulfite , asorbic acid or the methyl propyl esters of para hydroxy -benzoic acid , and the organic acids, benzoic and propanoic acids. Some hard gelatin capsules may contain 0.15 % w/w of sodium lauryl sulphate which functions as wetting agent , to ensure that the lubricated metal moulds are uniformly covered when dipped into the gelatin solution. .

20. Capsule size: For human use, empty capsules ranging in size from 000 the largest to 5 the smallest. Generally, hard gelatin capsule are used to encapsulate between 65 mg to 1 gram .   Capsule size Volume (ml) Height (cm) Diameter (cm) 000 1.37 2.61 0.99 00 0.95 2.33 0.85 0.68 2.17 0.76 1 0.50 1.94 0.69 2 0.37 1.80 0.63 3 0.30 1.59 0.58 4 0.21 1.43 0.53 5 0.13 1.11 0.49

21. MANUFACTURE OF EMPTY GELATIN CAPSULES : Steps involved in making empty gelatin capsules… Dipping Spinning Drying Stripping Trimming Joining Polishing 

22. Once raw materials have been received and released by Quality Control, the gelatin and hot demineralized water are mixed under vacuum in Stainless Steel Gelatin Melting System. From receiving tanks, the gelatin solution is transferred to stainless steel feed tanks. Dyes, opacifants, and any needed water are added to the gelatin in the feed tanks to complete the gelatin preparation procedure. From the feed tank, the gelatin is gravity fed to Dipper section.

23. Dipping : Pairs of the stainless steel pins are dipped into the dipping solution to simultaneously form the caps and bodies for 12sec. The dipping solution is maintained at a temperature of about 50 º C in a heated, jacketed dipping pan & pins are at 22ºc . Spinning : The pins are rotated to distribute the gelatin over the pins uniformly and to avoid the formation of a bead at the capsule ends it is rotated 2½ times by moving upward. 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, Here gently moving air which is precisely controlled for volume, temperature, and humidity, removes the exact amount of moisture from the capsule halves.

24. Stripping : A series of bronze jaws strip the cap and body portions of the capsules from the pins.  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. Polishing Pan Polishing : Acela-cota pan is used to dust and polish. Cloth Dusting : Capsule are rubbed with cloth. Brushing : Capsule are feed under soft rotating brush . Finished capsules are pushed onto a conveyer belt which carries them out to a container.

25. Preparation of filled hard gelatin capsules: In large scale or small preparations of filled hard gelatin capsules divided into the following general steps: Developing and preparing formulation. Filling the capsule shell Capsule sealing Cleaning and polishing the filled capsules Sorting.

26. Developing and preparing formulation : Diluents – diluents are the excipients that are usually present in the greatest concentration in a formulation and they make up the necessary bulk when the quantity of the active ingredient is insufficient to make up the required bulk eg. Lactose, maize starch, calcium sulphate etc. Lubricants and Glidants – which reduce powder to metal adhesion and promote flow properties eg. Magnesium stearate, talc. Wetting agents – which improve water penetration for poorly soluble drugs eg. Sodium lauryl sulfate Disintegrants – which produce disruption of the powder mass crospovidone, sodium starch glycolate.  

27. FILLING OF HARD GELATIN CAPSULES: Punch Method or Manual Filling. Hand Filling or Semi Automatic Capsules Devices. Automatic filling machine.  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 

28. 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. Funnel Method In this method measured quantity of powder is filled in bodies using funnel. If necessary, the powder is pressed in body by inserting glass rod in bodies, the cap may be fitted loosely and capsules are checked for fill weight. To ensure accuracy of dosage, each filled capsules should be weighed using an empty capsule of the same size as tare. Rotating the filled and sealed capsule b/w thumb and finger give complete and uniform filled appearance .

30. Hand Filling or Semi Automatic Capsules Devices Hand operated and electrically operated machines are in practice for filling the capsules but for small and quick dispensing hand operated machines are quite economical. A hand operated gelatin capsule filling machine consists of the following parts and is shown in figure . A bed with 200-300 holes. A capsule loading tray A powder tray A pin plate having 200 or 300 pins corresponding to the number of holes in the bed and capsule loading tray. A lever A handle A plate fitted with rubber top.

31. All parts of the machine are made up of stainless steel. The machines are generally supplied with additional loading trays, beds, and pin plates with various diameters of holes so as to fill the desired size of the capsules. These machines are very simple to operate, can be easily dismantled and reassembled  

32. Working: The empty capsules are filled into the loading tray which is then placed over the bed. By opening the cam handle, the bodies of the capsules are locked and caps separated in the loading tray itself which is then removed by operating the lever. The weighed amount of the drug to be filled in the capsules is placed in powder tray already kept in position over the bed. Spread the powder with the help of a powder spreader so as to fill the bodies of the capsules uniformly.

33. Collect excess of the powder on the platform of the powder tray. Lower the pin plate and move it downward so as to press the powder in the bodies. Remove the powder tray and place the caps holding tray in position. Press the caps with the help of plate with rubber top and operate the lever to lock the cap and body of the capsules. Remove the loading tray and collect the filled capsules in a tray. With 200 hole machine about 5000 capsules can be filled per hour and with 300 hole machine 7500 capsules can be filled per hour.

34. Automatic filling Machine

35. The machines for industrial -scale filling of hard gelatin capsules come in great variety of shapes and sizes, varying from semi- to fully automatic and ranging in output from 5000 to 15000 per hour. Automatic machines can be either continuous in motion, like a rotary tablet press, or intermittent, where the machine stops to perform a function and then indexes round to the next position to repeat the operation on a further set of capsules.

36. Finishing of Capsules: Cloth dusting : Capsule are rubbed with cloth that may or may not be impregnated with an inert oil. This procedure is a hand operated. Polishing Pan Polishing: Acela-cota pan is used to dust and polish which is lined with cheese or a polyurethane cloth to trap the dust as well as to impart a gloss to the capsules.

37. Brushing : Capsule are feed under soft rotating soft brush which serve to remove the dust from the capsule shell. this operation is accompanied by a vacuuming for dust removal. Sorting: ROTOSORT – It is a new filled capsule sorting machine sold by Eli- Lilly. It is a mechanical sorting device that removes loose powder, unfilled joined capsules, unfilled bodies and loose aps . It can handle upto1,50,000 capsules/hr

38. Manufacturing Defects in HGC

39. Soft Gelatin Capsules (Soft Elastic Capsules) Soft Gelatin capsules are one piece, hermetically sealed, soft gelatin shells containing a liquid, a suspension, or a semisolid. Soft Gelatin capsules are perfectly elegant and easily swallowed.

40. SHAPES OF SOFT GELATIN CAPSULES:

41. Advantages of soft gel capsules:   Ease of use - easy to swallow, no taste, unit dose delivery, temper proof. Versatile Accommodates a wide variety of compounds filled as a semisolid, liquid, gel or paste. Wide variety of colors, shapes and sizes Immediate or delayed drug delivery-can be used to improve bioavailability by delivering drug in solution or other absorption enhancing media

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

43. Properties of Gelatin: Bloom or gel strength : The bloom or gel strength is a measure of the cohesive strength of cross-linking that occurs between gelatin molecules & is proportional to the molecular weight of the gelatin. The cost of gelatin is directly proportional to its bloom or gel strength and thus is an important factor in the cost of soft capsules. Higher the bloom strength, more physically stable the capsule shell. Bloom range:50-250 g. Low Bloom: gel strength below 120 g.  Medium Bloom: gel strength between 120 and 200 g. High Bloom: gel strength above 200 g.

44. Viscosity of gelatin : It is a measure of the chain length & manufacturing characteristics of gelatin film. The required viscosity of gelatin lies in between 25-45mps. Iron content: It is always present in raw gelatin as well as water used in mfg. excess qty. of iron can effect FD &C & react with organic compounds. Hence, iron is used in the conc of not more than 15ppm.

45. MANUFACTURE OF SOFT GELATIN CAPSULES: Plate process Rotary die process Accogel machine Bubble Method

46. Plate process:  It is the oldest commercial method Place the gelatin sheet over a die plate containing numerous die pockets. Application of vacuum to draw the sheet in to the die pockets. Fill the pockets with liquid or paste. Place another gelatin sheet over the filled pockets, and Sandwich under a die press where the capsules are formed and cut out.

47. Rotary die press: In this process, the die cavities are machined into the outer surface of the two rollers. Gelatin mass is fed by gravity to a metering device (spreader box), which controls the flow of the mass onto air cooled (13-14 C) rotating drums. Gelatin ribbons of controlled thickness(±10) are formed . The ribbons are fed through a mineral oil lubricating bath, over guide rolls and then down the wedge and the die rolls.

48. The material to be capsulated flows by gravity into a positive displacement pump. The pump accurately meters the material through the leads and wedge into the gelatin ribbons between the die rolls. Two plasticized gelatin ribbons are continuously and simultaneously fed with the liquid or paste fill between the rollers of the rotary die mechanism. As the die rolls rotate, the convergence of the matching die pockets seals and cuts out the filled capsules. The sealing of the capsules is achieved by mechanical pressure on the die rolls and the heating (37-40ºC) of the ribbons by the wedge.

49. ROTARY DIE MACHINE:  

50. Accogel Capsule Machine: It consists of mainly 3 parts: M easuring roll Die roll S ealing roll As the measuring roll and die rolls rotate, the measured doses are transferred to the gelatin-linked pockets of the die roll . The continued rotation of the filled die converges with the rotating sealing roll where a second gelatin sheet is applied to form the other half of the capsule . Pressure developed between the die roll and sealing roll seals and cuts out the capsules.

51. Seamless gelatin capsules OR Bubble method: Another method of making soft capsules takes advantage of the phenomenon of drop formation. The essential part of the apparatus consists of two concentric tubes. Through the inner tube flows the medicament and, through the surrounding outer tube, the gelatin solution. The medicament, therefore, issues from the tube surrounded by gelatin and forming a spherical drop. This is ensured by allowing the drop to form in liquid paraffin in which the gelatin is insoluble. Regular induced pulsations cause drops of the correct size to be formed, and a temperature of 4° C ensures that the gelatin shell is rapidly congealed. The capsules are subsequently degreased and dried.

52. Vehicles used in soft gelatin capsules: Water immiscible, volatile or more likely volatile liquids such as vegetable oils, mineral oils, medium-chain triglycerides and acetylated glycerides. Water miscible, nonvolatile liquids such as low molecular weight PEG (400,600) have come into use more recently because of their ability to mix with water readily and accelerate dissolution of dissolved or suspended drugs.

53.   There are three primary types of inner fill materials:   1. Neat Substance, especially oily liquids eg. Cod liver oil capsules 2. Solution Fills : Active dissolved in a carrier   Oils such as soybean oil and Miglyol 812 (neutral oil, triglycerides of medium chain fatty acids) Polyethylene Glycols: especially PEG 400 -600   Other solvents: Any other solvent, which doesnot degrade or solubilize the gelatin shell, i.e., dimethyl isosorbide, surfactants, diethylene glycol monoethly ether.    

54. 3. Suspension Fills : Active dispersed in a carrier.   Suspensions can accommodate about 30% solids before viscosity and filling become a problem   Suspensions can be heated up to 35ºC to decrease viscosity during the filling process   Suspended solids must be smaller than 80 mesh -- mill or homogenize before filling to prevent needles from clogging during filling.  

55. Base Adsorption of solids to be suspended in soft gelatin capsules Base adsorption is expressed as the number of grams of liquid base required to produce a capsulatable mixture when mixed with one gram of solid(s). The base adsorption of a solid is influenced by such factors such as the solids particle size and shape, its physical state (fibrous, amorphous, or crystalline), its density, its moisture content, and its oleophilic or hydrophilic nature.

56. In the determination of base adsorption, the solid(s) must be completely wetted by the liquid base. For glycol and nonionic type bases, the addition of a wetting agent is seldom required, but for vegetable oil bases, complete wetting of the solid(s) is not achieved without an additive. Soy lecithin, at a concentration of 2 to 3 % by weight of the oil, serves excellently for this purpose, and being a natural product, is universally accepted for good drug use. Increasing the concentration above 3 % appears to have no added advantage.

57. A practical procedure for determining base adsorption and for judging the adequate fluidity of a mixture is as follows : Weigh a define amount of the solid (40g is convenient) into a 150 ml tared beaker. In a separate 150 ml tared beaker, place about 100 g of the liquid base. Add small increments of the liquid base to the solid, and using a spatula, stir the base into the solid after each addition until the solid is thoroughly wetted and uniformly coated with the base.

58. This should produce a mixture that has a soft ointment like consistency. Continue to add liquid and stir until the mixture flows steadily from the spatula blade when held at a 45-degree angle above the mixture The base adsorption is obtained by means of the following formula –   Weight of the base = Base Adsorption Weight of the solid

59. MINIM PER GRAM” FACTOR (M/g) OF THE SOLID(S ) The base adsorption is used to determine the “minim per gram” factor (M/g) of the solid(s). the minim per gram factor is the volume in minims that is occupied by one gram (S) of the solid plus the weight of the liquid base (BA) required to make a capsulatable mixture. The minim per gram factor is calculated by dividing the weight of the base plus the gram of solid base (BA+ S) by the weight of the mixture (W) per cubic centimeter or 16.23 minims (V). a convenient formula is-   (BA + S) x V = M/g W

60. Thus lower the base adsorption of the solid (s) and higher the density of the mixture, the smaller the capsule will be. This also indicates the importance of establishing specifications for the control of those physical properties of a solid mentioned previously that can affect its base adsorption.

61. The final formulation of a suspension invariably requires a suspending agent to prevent the settling of the solids and to maintain homogeneity prior to, during, and after capsulation. The nature and the concentration of the suspending agent vary. In all instances the suspending agent used is melted in a suitable portion of the liquid base, and the hot melt is added slowly, with stirring, into the bulk portion of the base, which has been pre-heated to 40 degrees prior to the addition of any solids. The solids are then added, one by one, with sufficient mixing between additions to ensure complete wetting. Incompatible solids are added as far apart as possible in the mixing order to prevent interaction prior to complete wetting by the base.  

62. EVALUATION OF CAPSULES: (1) Content uniformity (2) Disintegration test . (3) Weight variation test (4)Dissolution test.  ( 5) Moisture permeation test

63. Content uniformity: For an individual capsule, the amount of active ingredient should be within the range of 85% to 115% of the label amount for 9 of 10 capsules, with no unit outside the range of 75% to 125% of label amount. If Fail- Repeat on 20: Pass if NMT 3 out of 30 outside 85% to 115% with no unit outside the range of 75% to 125% of label amount.

64. Disintegration test for capsules : Place 1 capsule in each of the 6 tubes of the basket & suspend the assembly in water at 37℃ ± 2ºC, which is repeatedly immersed for 29-32 cycles per min. The capsules pass the test if no residue of drug or other than fragments of shell remains on No. 10 mesh screen of the tubes.

65. Disintegration time of various capsules according to IP Capsule Disintegration time (min) Hard capsule 30 Soft capsule 60 Enteric Capsules 60 If fail- Test on additional 12, 16/18 must disintegrate completely

66. 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 acceptable range . Average mass (mg) Percentage deviation (%) Less than 300 ± 10 300 or more ± 7.5

67. If this requirement is not met, then the weight of the contents for each individual capsule is determined and compared with the average weight of the contents. The contents from the shells can be removed just by emptying or with the help of small brush. From soft gelatin capsules the contents are removed by squeezing the shells which has been carefully cut. The remainder contents are removed by washing with a suitable solvent. After drying the shells, they are weighed and the content weights of the individual capsules are calculated. The requirements are met if (1) not more than 2 of the differences are greater than ± 10 % of the average net content and (2) in no case the difference is greater than ± 20 %.

68. Moisture permeation test: Acc. to U.S.P the unit dose container is packed along with dehydrated pellets , which have the property of changing color in the presence of moisture. The weight of test capsule is compared with the under test capsules. Diff. in weights gives the amount of moisture absorbed

69. Dissolution test for capsules: Place 1000 ml of water having a temp. of 36.5º to 37.5º into the vessel. Place specified number of capsules in basket & adjust the speed to 100 rpm. Withdraw req. volume for every 10min time interval. Filter and determine the amount of active ingredient. The sample passes the test if the amount of active ingredients in the solution is not less than 70% of the stated amount.

70. Stage Number of capsule tested Acceptance criteria S1 6 Each unit is not less than Q + 5%. S2 6 Average of 12 units (S1+ S2) is equal to or greater than Q, and no unitis less than Q –15%. S3 12 Average of 24 units (S1+ S2+ S3) is equal to or greater than Q, not more than 2 units are less than Q –15%, and no unit is less than Q –25% The quantity Q, is the specified amount of dissolved active substance, expressed as a percentage of the labeled content;

71. PACKING & STORAGE OF CAPSULES: Capsules should be packed in well closed glass & plastic container & stored at temp. not exceeding 30ºC. 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 desiccan t 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.

72. Capsules are individually protected by enclosing in strip & blister packaging. In strip packing the capsule is hermetically sealed within the strips of an aluminum or plastic film. In blister packs, a press on the blister forces the capsule through the backing strip. Capsules have a larger shelf life in unopened glass bottles than in strip pack & but this is reversed. 

73. 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.

74. CAPSULE STABILITY: Unprotected soft capsules (i.e., capsules that can breathe) rapidly reach equilibrium with the atmospheric conditions under which they are stored. This inherent characteristic warrants a brief discussion of the effects of temperature and humidity on these products, and points to the necessity of proper storage and packaging conditions and to the necessity of choosing an appropriate retail package. The variety of materials capsulated, which may have an effect on the gelatin shell, together with the many gelatin formulations that can be used, makes it imperative that physical standards are established for each product.

75. As the humidity is increased, with in a reasonable temperature range, the shell of the unprotected control capsule should pick up moisture in proportion to its glycerin and gelatin content.   The total moisture content of the capsule shell, at equilibrium with any given relative humidity within a reasonable temperature range, should closely approximate the sum of the moisture content of the glycerin and the gelatin when held separately at the stated conditions.  

76. Temperature Humidity Effect on Capsule shell 21-24 ° C 60% Capsules become softer , tackier and bloated Greater than 45% More rapid and pronounced Greater than 24 ° C effects – unprotected capsules melt and fuse together The effect of temperature and humidity on capsule shell has been illustrated in Table 2.  

77.  Capsules containing water-soluble or miscible liquid bases may be affected to a greater extent than oil-based capsules, owing to the residual moisture in the capsule content and to the dynamic relationship existing between capsule shell and capsule fill during the drying process. The capsule manufacturers routinely conduct accelerated physical stability tests on all new capsule products as an integral part of the product development program.

78. The following tests have proved adequate for determining the effect of the capsule shell content on the gelatin shell. The tests are strictly relevant to the integrity of the gelatin shell and should not be confused as stability tests for the active ingredients in the capsule content. The results of such tests are used as a guide for the reformulation of the capsule content or the capsule shell, or for the selection of the proper retail package.  

79. Test conditions Observation 80 % RH at room temperature in an open container. Capsules are observed periodically for 2 weeks, both gross and subtle effects of the storage conditions are noted and recorded. 40 ○ C in an open container. The control capsule should not be affected The test conditions for such accelerated physical stability tests are shown in table 3.

80. Thank You