Capsules

Hard Capsule
Soft Capsule

1. CAPSULES Zulcaif Ahmad 

2. CAPSULES "Capsules are solid dosage forms in which one or more medicaments are enclosed in a water soluble bio degradable shell made up of gelatin"

3. TYPES OF CAPSULES

4. HARD SHELLED CAPSULES “ Hard-shelled capsules, which are typically made using gelatin and contain dry, powdered ingredients” These are made in two halves : Lower-diameter "body" that is filled T hen sealed using a higher-diameter "cap".

5. SOFT-SHELLED CAPSULES Soft-shelled capsules, primarily used for oils and for active ingredients that are dissolved or suspended in oil.

6. Capsules Are Made From Aqueous Solutions Of Gelling Agents Like: Animal protein, mainly gelatin
Plant polysaccharides or their derivatives like carrageenans and modified forms of starch and cellulose.
Other ingredients can be added to the gelling agent solution like: plasticizers such as glycerin or sorbitol to decrease the capsule's hardness, coloring agents, preservatives, disintegrants, Lubricant surface treatment

7. COMPONENTS OF CAPSULES 1. Gelatin 2 . Certified dyes 3 . Sugar 4 . Water - 12 to 16 % but may vary depending on the storage condition 5. Sulfur dioxide (0.15%) - prevent decomposition during manufacture 6 Opaquants /Opacifying agent - titanium dioxide

8. GELATIN Gelatin or gelatine (from Latin: gelatus meaning "stiff", "frozen") is a translucent, colourless, brittle (when dry), flavourless foodstuff, derived from collagen obtained from various animal by-products. It is commonly used as a gelling agent in food, pharmaceuticals, photography, and cosmetic manufacturing.
Gelatin is an irreversibly hydrolyzed form of collagen

9. TYPES OF GELATIN TYPE A Derived from acid treated precursor that exhibits an iso electric point at pH-9. It is manufactured mainly from animal bones TYPE B Derived from alkali treated precursor that exhibits an iso electric point at pH-4.7. It is manufactured mainly from pork skin

10. HARD GELATIN CAPSULES Also referred to as “DFC” Dry Filled Capsule. CAPSULE SIZES: For human use, empty capsules ranging in size from 000 (the largest) to 5 (the smallest) are commercially available. Generally encapsulates between 65mg to 1g of powdered material. For veterinary use: No's 10, 11and 12 having capacities of 30, 15 and 7.5 g, respectively

11. ADVANTAGES OF CAPSULES Ease of use due to the fact that it is smooth, slippery and easy to swallow . Suitable for substances having bitter taste and unpleasant odor . As produced in large quantities it is economic, attractive and available in wide range of colors . Minimum excipients required . Little pressure required to compact the material . Unit dosage form . Easy to store and transport.

12. DISADVANTAGES OF CAPSULES Not suitable for highly soluble substances like potassium chloride, potassium bromide, ammonium chloride, etc Not suitable for highly efflorescent or deliquescent materials . Special conditions are required for storage.

13. Steps involved in making empty gelatin capsules with peg/pin method… Dipping Spinning Drying Stripping Trimming and Joining Polishing MANUFACTURING OF HARD GELATIN CAPSULES The process of capsule shell production with the pin method: Dipping→ Drying → Stripping→ Trimming→ Joining → Polishing

14. DIPPING : Pairs of the stainless steel pins are dipped into the dipping solution to simultaneously form the caps and bodies. The dippin solution is maintained at a temperature of about 50 degree centigrade in a heated ,jacketed dipping pan. SPINNING: The pins are rotated to distribute the gelatin over the pins unifomly and to avoid the formation of a bead at the capsule ends. 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 of bronze jaws strip the cap and body portions of the capsules from the pins.

15. TRIMMING AND JOINING The stripped cap and body portions are trimmed to the required length by stationary knives . After trimming to the right length, the cap and body portion are joined and ejected from the machine. 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.

16. During production the thickness of the capsule wall is controlled by the viscosity of the gelatin solution, speed and time of dipping. Empty capsules should not be subjected to temperature above 38 ºC (might destroy the capsule shells such that they can not be handled in the Filling equipments) Empty capsules should maintain moisture Content between 12% and 15%. Below 10% they become brittle Above 16% they might increase in size (causing problems inthe filling equipment) or they might become soft.

17. CAPSULE FILLING MACHINE It is the mechanical device that fills the powders (active ingredients and the mixtures of active ingredients with combinations of different excipients) into hard or soft gelatin capsules. Capsule filling machines are used commonly in industrial and pharmaceutical purpose. Millions of capsules can be filled by using different varieties of capsule filling machines which are provided by different manufacturers.

18. Hard capsule FILLING Bench scale filling .(for small scale filling) - Manual filling machine eg: feton capsule filling machine 2) Industrial scale-filling. Comes in varying shapes and sizes - semi automatic machine - fully automatic machine

19. At present about 9 manufacturing companies supplies the capsule filling machines with different models . The following famous companies which provides capsule filling machines are Eli Lilly and company indianapolis IN Farmatic SNC , Bologna, Italy Macofar SAS, Bologna, Italy Hofliger and Karg, Waiblingen , Germany mG2 S.P.A., Bologna, Italy Osaka, Osaka, Japan Parke-Davis and company, Detroit, MI Perry Industries, Green BayWI Zanasi Nigris, S.P.A., Bologna, Italy The largest number of total machines are supplied by Lilly and Parke-Davis. The method of operation and the description of the machines are similar in these two companies .

20. The nine famous companies which provides capsule filling machines of different models and types are as follows: Lilly capsule filling machine, Lilly ROTOFIL capsule filling machine. Farmatic Model 2000/15, 2000/30 and 2000/60 capsule filling machine. Hofliger and Karg model GKF-303, GKF-602, GKF-1500 and GKF-2500 capsule filling machine. Macofar:MT-12, MT-13/1 and MT-13/2 capsule filling machine. mG2:Model G36/4, G36/2, G36, G37N and G38 capsule filling machine. Osaka Model 180 capsule filling machine. Perry: Perry Model CF ACCOFIL capsule filling machine. Zanasi:Zanasi Model LZ-64 and AZ-20 capsule filling machine

21. What is the common working principle of all capsule filling machines?

22. Bench scale filling Bed – 200-300 holes Powder tray Sealing plate with rubber top lever loading tray with 200-300 holes Pin plate with 200-300 holes scraper Cam handle

23. HAND OPERATED CAPSULE FILLING MACHINE It consist of a bed having 200-300 hole, 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, a cam handle. The empty capsules are filled in the loading tray and it is palced 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 the 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.

24. 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 and bodies. The loading tray is then removed and filled capsules are collected. With a 200 hole machine, about 5000 capsules can be filled in one hour, whereas in a machine having 300 holes, about 7500 capsules can be filled in one hour.

25. JAANSUN CAPSULE FILLING MACHINE

26. Semi-Automatic Capsule Filling machine There are 3 stations in this semi-automatic capsule filling machine orientation of capsule powder filling capsule closing.

27. THE FIRST STATION :ORIENTATION OF CAPSULES The functions of first station include : capsule feeding Aligning insertion into bores of holding ring vacuum is used for separating capsule cap and body in first station. After orientation of capsule, capsule cap can stay in upper holding ring and capsule body can stay in lower holding ring.

28. THE SECOND STATION:POWDER FILLING Separate the holding ring,put the lower (body) holding ring on the rotary table, pull the powder hopper over the lower (body) holding ring, then auger inside powder hopper starts to run and fill powder into the capsule body . While Iower holding ring turns one circle, push powder hopper to its original psition .

29. THE THIRD STATION:CAPSULE CLOSING Put upper holding ring and lower holding ring together, then position intact holding ring in front of peg ring .closing plate is pivoted to a position approximately 180 degrees Pneumatic pressure is applied to peg ring which finally push capsules inside the bores of holding ring the finished capsules will be collected into the container .

30. Lilly/Parke-Davis Storage hopper Rectifying unit Two piece filling ring Powder hopper Peg ring Closing plate Collecting chamber

31. SEMI AUTOMATIC MACHINE

32. AUTOMATIC CAPSULE FILLING MACHINE Automatic Capsule Filling Machine has been designed and developed to fill hard gelatin capsules with powder or pellets. It is an extremely durable and reliable machine that fills dosages to the highest accuracy. It can be applicable to the widest range of capsules at all sizes and guarantee the integrity of all capsules.

33. Fully automatic

34. The housing and surface are covered with stainless steel 304. All contact parts of medical powders are made from a corrosion resistant stainless steel 316. Parts are made by CNC computer machine. All parts are standardized and easy to substitute. Capable of filling 6 capsules at a time with operation from 10 stations. Accurate operation for orientation, opening, filling, joining and ejecting of the capsules Compulsory spiral feeding in the powder hopper to ensure powder feeding and filling. Dual capsule-opening design to ensure all capsules are opened. Electrical impact protection device to prevent any further damage. The machine will stop automatically in the event of collision.

35. Safety Sensing System to shut the machine down automatically in the event of problems when no capsules, no powder, door is opened, and abnormal load for the machine are detected. Automatic vacuum removal of the air in the dosing tube to give more accurate weight of the filled capsules. . Exclusive dosing tube system, temperature of the powder will not rise during the filling process. Adjustable compression piston in dosing trube to adjust the powder volume without change parts.

36. 40000 capsules per hour 80000 capsules per hour 160000 capsules per hour Farmatic Model 2000/60 Capsule filling machine Farmatic offers three models of filling equipments 2000/15 2000/30 2000/60 FARMATIC SNC Model capacity

37. HOFLIGER KARG AUTOMATIC CAPSULE FILLING MACHINE H & K line consists basically of four machine models. GKF-303 GKF-602 GKF-1500 GKF-2500 Hofliger and Karg

38. H & K model GKF-602 Empty capsule storage hopper Rectifier Bulk powder storage hopper Capsule body transport segment Closing station Filled capsules ejection station

39. Macofar Macofar line of equipments consists of three models. Low to medium capacity machines MT-12 35,000 capsules per hour MT-13/1 5,000 capsules per hour MT-13/2 10,000 capsules per hour MODEL CAPACITY

40. Five models of continuous motion filling machines are offered by mG2. G36/4 150 capsules per minute G36/2 300 G36 600 G37N 1600 G38 1000 mG2 MODEL CAPACITY

41. High capacity, continuous motion machine . The only model available is R-180 : 70000 to165000 capsules per hour Can be modified to 400000 capsules per hour . OSAKA

42. OSAKA MODEL R-180 SEMI AUTOMATIC CAPSULE FILLING MACHINE

43. ZANASI Nine different units in four model lines LZ-64 : 4000 capsules per hour AZ-20 : 9000 TO 20000 capsules per hour BZ series BZ-40 : 30000/hr BZ-72 : 60000/hr BZ-110 : 110000/hr BZ-150 : 150000/hr Z-5000 series Z-5000-R1 : 70000/hr Z-5000-R2 : 110000/hr Z-5000-R3 : 150000/hr

44. ZANASI AUTOMATIC CAPSULE FILLING MACHINE

45. CAPSULE FILLING OF HARD SHELL CAPSULES

46. HARD GELATIN CAPSULES MANUAL FILLING METHOD(PUNCH METHOD) HAND OPERATED METHOD AUTOMATIC OPERATED FILLING MACHINES

47. MANUAL FILLING METHOD Used for filling a small number of capsules in the pharmacy, at the prescription counter. The ingredients are triturated to fine & uniform powder. The powder is placed on a powder paper or ointment slab and smoothed with a spatula to a height approximately half the length of the capsule body

48. The base of the capsule is held vertically and the open end is repeatedly pushed or "punched" into the powder until the capsule is filled; The cap is then replaced to close the capsule. Each filled capsule is weighed using an empty capsule as a counterweight. Powder is added or removed until the correct weight has been placed in the capsule. The filled capsule is tapped so that no air spaces are visible within the contents

49. Hand Operated Method Pharmacists that prepare capsules on a regular or extensive basis may use hand-operated capsule machines. These machines are available in capacities of 24, 96, 100, and 144 capsules. machine is the tray used to hold the fill over the empty capsules, the spreader and roller used to distribute the fill material in the tray and permit it to enter the capsules uniformly, and the packer used to compact the fill in the capsules

50. AUTOMATIC OPERATING CAPSULE MACHINES Machines developed for industrial use can automatically remove the caps from empty capsules, fill the capsules, replace the caps, and clean the outside of the capsules at a rate of up to 1,65,000 capsules and greater per hour.

51. SEALING OF CAPSULES TAMPER-EVIDENT CAPSULES are made sealing the joint between the two capsule parts. DISTINCTIVE LOOKING CAPSULES can be made by sealing capsules with a colored band of gelatin, which cant be restored without expert sealing. HEA T WELDING PROCESS can also be used, that fuses capsules cap through the double wall thickness at junction LIQUID WETTING AGENT that lowers the M.P in contact areas of capsule cap & body & then thermally bonds the two parts using low temperatures

52. Coni-snap hard gelatin capsules A recent innovation in capsule shell design, where the two halves of the capsule shells are enable to be positively joined through locking grooves in the shell walls. The two grooves fit into each other and ensure reliable closing of the filled capsule. Opening of such capsule is difficult with increasing security of the contents of the capsule

53. CLEANING & POLISHING On small scale capsules may be cleaned individually or in small numbers by rubbing them with a clean guaze or cloth. On large scale many CAPSULE FILLING MACHINES with a cleaning vacuum that removes any extraneous material from the capsule as they exit the equipment. (ACCELACOTA APPARATU..S )

54. STORAGE CONDITIONS Hard gelatin capsules are stored in a tightly closed glass or plastic containers, protected from dust and extremes of humidity and temperature . Minimum Ideal Maximum Relative humidity 40% 50% 60% Temperature 15 c 20 o c 25 o c

55. These capsules contain 12 - 16% water but water content vary according to the storage conditions. Capsules become brittle in low humidity but are flaccid and lose their shape if stored in high humidity. They do not protect hygroscopic materials from atmospheric water vapor as moisture can diffuse through the gelatin wall. When storage temperature condition is high the quality of the hard gelatin capsules are affected

56. ADVANTAGES OF HARD GELATIN CAPSULE Simpler manufacturing process. Fewer production steps Less manufacturing equipments. Reduces stability problems with sensitive drugs. Granules, powders, liquids, semi-solid formulations and mini tablets can easily be filled alone or in combination. Reduces stability problems with sensitive drugs.  Printing options, axially or radially , provide greater possibilities in branding protection

57. <<<SOFT GELATIN CAPSULES>>>>>

58. SOFT GELATIN CAPSULES “ Soft gelatin capsules are one piece , hermetically sealed , and are made up of gelatin in which glycerin or polyhydric alcohol (sorbitol) are added , containing liquid , suspension or semisolid enclosed in matrix . ”

59. CHARACTERISTICS They may be oblong, oval, or round. They Vary in sizes They may be single colored or two toned

60. DESCRIPTION Drug present in these capsules may be suspension, solution or emulsion Ingredients that are solid at room temperature can also be encapsulated in softgels if they are at least semisolids below 45degree. The softgels can be coated with enteric resistant or delayed release coating material.

61. CAPSULE SHELL The capsule shell is basically composed of Gelatin, a plasticizer & water it may contain additional ingredients such as preservative, coloring & opacifying agents, flavorings, sugars, acids & medicaments to achieve desired effects Capsule shell WATER: NOT MORE THAN 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 . 2. 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

62. 3.COLOUR: Used in shell has to be darker than colour of encapsulating material colours may be natural or synthetic. 4.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. Concentration of opacifier may be up to 0.5 % 5.Chelating Agents: Iron is always present in raw gelatin, & should not contain iron more than 15 ppm. Additionally chelating agent may be used for preventing the reaction of iron with materials or colours.

63. "TYPICAL FORMULA FOR GELATIN SHEET" A typical gel mass formula for making soft gelatin capsules would be: Gelatine 35-45% Plasticizer 15-25% Water ~40% Dye / Pigment as needed Opacifier as needed Other (flavor, sugar,) as needed (((1 part gelatin, 1 part water, 0.4-0.6 part plasticizer)))

64. " GELATIN MASS MANUFACTURE > The gel is prepared in a 300-litre stainless steel vessel >Gelatin powder is mixed with water and glycerine. Heating. Stirring. The molten gelatin mass is formed >It is decanted into 200-kg mobile vessels >Turbine mixing where colours and flavours can be added. It ensures consistency of gelatin mass >This mass is kept at a constant temperature until it is needed for the next stage of the process

65. “ CAPSULE CONTENT " Content may be liquid, or a combination of miscible liquids Solution of a solid(s) in a liquid(s) or Suspension of a solid(s) in a liquid. It can be a liquid like a volatile oil composition E.g. Vegetable oils like arachis oil or aromatic or aliphatic hydrocarbons, ethers, esters, or alcohols. Solids that are not Sufficiently soluble in liquids or in combination of liquids are capsulated as Suspension. Suspending agents used are Lecithin, Soyabean oil, yellow wax

66. Orally administered: Solutions or suspensions that release contents in stomach. Chewable softgels: Highly flavored shell is chewed to release drug liquid fill matrix. suckable softgels: gelatin shell to be sucked & liquid matrix or just air inside capsule Meltable softgels: meltable softgels are used for pessaries or suppositories . Types of softgels

67. Manufacture of softgels: 1.plate process : It involves pressing 2 sheets of wet gelatin together b/w 2 molds. Each die mold contained pockets into which gelatin sheet was pressed & into which medication was filled. Pressure b/w 2 plates enable each capsule to cut out from mold & capsules were subsequently dried.

68. 2.ROTARY DIE PROCESS *Robert P scherer in 1933 invented this method *the material to be encapsulated flows by gravity <<Principle>> “Involves the formation of a heat seal b/w two gelatin ribbons, simultaneous with dosing of fill liquid into each capsule”

69. Before encapsulation, two processes are carried out: 1. Gell mass (providing softgel shell) 2. Fill matrix (for softgel contents) GELL MASS prepared by dissolving gelatin in water at approx, 80 degrees under vacuum and addition of plasticizers ( glycerol) * once gelatin is fully dissolved then other components are added (colorants, flavourants, preservatives )

70. Rotary die process (contd.) ENCAPSULATION : molten gel is pumped to machine and two thin ribbons of gelatin formed . *thickness of each gel ribbon is controlled in range of 0.5-1.5mm* Ribbons pass over rollers and are fed between two rotating die cylinders that determine the size and shape of capsules, forming two halves of capsule ribbons converge next to a fill injector Here appropriate volume of fill material is measured and dispensed by a pump die assembly rotates, filled capsule halves sealed together by heat and pressure application and ejected

71. ROTARY DIE PROCESS (CONTD.) FINISHING : drying in tumblers containing lint- free towels and large volume of forced air Capsules transferred To trays and placed in low- humidity drying rooms, at room temp, to remove excess moisture water content of the gelatin shell at start --- around 30% water content of the gelatin shell when evaporation end -- 8 or 9%

72. The following should be monitored/controlled: Gelatin temperature Fill temperature Ribbon thickness Seal or seam width Fill quantity pressure ( b/w rotary dies, controls softgel shape and final cut out from gel ribbon

73. Typical Parts Of Machine 1.Spreader Box 2.Cooling Drum 3. Oil Lubrication Roller 4. Gelatin Ribbon Guide Roller 5.Die Roll 6.Injection Wedge 7.Capsule Stripper 8.Conveyor 9.Medicine Filling Hopper 10.Medicine Filling Pump

74. "Accogel Capsule Machine" Or Stern machine, uses a system of rotary dies but is unique in that it is only machine that can successfully fill dry powder into a soft gelatin capsule. Measuring roll rotates directly over the die roll, and the pockets in the 2 rolls are aligned each other. Measuring roll-powder or granular fill material under vacuum. Die roll-plasticized sheet under vacuum Sealing roll-second gelatin sheet applied to form other half of capsule Pressure developed between die roll and sealing roll seals and cuts out the capsules

75. <<< PRODUCT QUALUTY CONSIDERATIONS>>>

76. >>>> GENERAL OFFICIAL Q.C. TESTS TO E PERFORMED ON ALL TYPES OF CAPSULES <<< ((ACCORDING TO B.P.)) 1.Uniformity of dosage unit 2.uniformity of content 3.uniformity of mass 4.dissolution 5.Storae 6.labelling

77. ** IN PROCESS TESTS gel ribbon thickness and uniformity across the ribbon seal thickness weight of capsule fill and its variation from capsule to capsule weight of capsule shell and its variation from capsule to capsule moisture level of the capsule shell before and after drying

78. ** FINISHED PRODUCT TESTS Permeability and sealing potency and impurity content average weight and weight variation uniformity of content disintegration dissolution moisture content microbial content

79. 1. permeability and sealing: capsules are tested for physical integrity, by visual inspection like, absence of breakage or open cap and body 2. POTENCY AND IMPURITY CONTENT: All capsules are tested for drug contents, as well as impurities and other substances must meet pre-defined specifications for a batch to be acceptable

80. 3. Weight variation test FOR HARD CAPSULES: 20 capsules are individually weighed Test complies if individual capsule falls with in 90-110% of average weight

81. 6. microbial content: capsules are tested to ensure lack of growth of bacteria and mold by microbiologiocal testing. test is carried out by incubating the capsule contents in growth medium and counting colonies formed after pre-defined period of time .

82. REFERENCE Pharmaceutical Dosage Forms and Drug Delivery, Second Edition By Ram I. Mahato http://www.pharmacopeia.cn/v29240/usp29nf24s0_c711.html http://www.authorstream.com/Presentation/aSGuest89715-887369-soft-gelatin-capsules/ http://www.slideshare.net/Ramyapriya7/quality-control-of-capsules