Chapter on Capsule
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This document provides information on hard gelatin capsules, including their production process, equipment used, quality control tests, and sizes. It discusses the preparation of gelatin, molding capsule halves, drying, trimming, joining, filling, sealing, and packaging processes. Key equipment for filling capsules are also outlined, including elevators, filling machines for powders, granules and liquids, air displacement units, metal detectors, and sorting machines. Standard operating procedures and environmental conditions for capsule filling are also provided.
Chapter on Capsule
- 1. SEMINAR ON 1 By:Rajesh L. Dumpala (B.Pharm, M. Pharm.) PhD. ( Pursuing) Research Scientist, Alembic Research Centre. Vadodara E.Mail:-rdumpala64@gmail.com
- 2. CONTENT1. INTRODUCTION TO CAPSULE 1.1 HARD GELATIN CAPSULE 1.1.1 PREPARATION OF HGC WITH PLANT LAYOUT 1.1.2 INDUSTRIAL SCALE EQUIPMENTS 1.1.3 STANDARD OPERATING PROCEDURE 1.1.4 QUALITY CONTROL TESTS 1.2 SOFT GELATIN CAPSULE 2. STUDY QUESTIONS 3. REFERENCES 2
- 3. 1.1 HARD GELATIN CAPSULE CAP BODY 3
- 4. HARD GELATIN CAPSULE SIZES AND THEIR APPROXIMATE CAPACITIES 4
- 5. CHANGE ROOM(M) CHANGE ROOM(F) OFFICE DISPENSING MAT. STORE DISPENSING AREA FILL MATERIAL STORE ROOM EMPTY CAPSULE STORE ROOM CAPSULE FILLING AREA AIRLOCK AIRLOCK STORE ROOM BLISTER PACKING STRIP PACKING PACKAGING AREA OFFICE SPARE PARTS I.P.Q.C INTERMEDIATE STORE DRYING SERVICE UNCLEANED CONTAINER Environment condition Humidity: Not more than 35% RH Temperature: Not more than 25% 5
- 6. COMPOSITION OF HARD GELATIN CAPSULE SHELL 1) GELATIN -- BLENDS OF BONE AND PORK SKIN GELATIN 2) COLORANTS --F,D&C COLOR --CERTIFIED DYE 3) OPACIFYING AGENT –TITANIUM DIOXIDE 4) PLASTICIZERS --PHTHALATE DERIVATIVE --GLYCERIN --CASTOR OIL -- PROPYLENE GLYCOL 5) PRESERVATIVES -- BENZOIC ACID -- PARABENS -- SULPHUR DIOXIDE 6) MOISTURE -- 12 – 15 % 6
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- 9. Here, the capsules are moulded onto stainless steel Pin Bars which are dipped into the gelatin solution. 9
- 10. Once dipped, pin bars rise to upper deck allowing the cap and body to set on the pins. 10
- 11. Temperature and humidity controlled air is blown over the mould pins to remove excess water content from the capsule halves. Humidity, temperature and gelatin viscosity is precisely monitored throughout the process. 11
- 12. Once drying is complete, the Pin Bars enter the Table section which positions the capsule halves for stripping from the Pins in the automatic section. 12
- 13. In the Automatic section, capsule halves are individually stripped from the Pins. 13
- 14. The cap and body lengths are precisely trimmed to a ±0.15 mm tolerance. 14
- 15. The capsule bodies and caps are joined automatically in the joiner blocks. 15
- 16. Finished capsules are pushed onto a conveyer belt which carries them out to a container. Capsule quality is monitored throughout the production process including size, moisture content, single wall thickness, and color. 16
- 17. Capsules are sorted and visually inspected on Inspection Stations. Perfect capsules are imprinted with the client logo on high-speed capsule printing machines. Capsules are now ready to be sterilized and packaged. 17
- 18. Special computer controlled process system monitors and controls total capsule manufacturing to ensure optimum out-put of highest quality capsules. 18
- 19. CAPSULE FILLING EQUIPMENT • Daily output 200,000 capsules 19
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- 22. Product conveying system 3.Air displacement unit Empty capsule sorter elevator Automatic capsule filling machine Check weigher Capsule sorter Dedusting & polishing machine Metal detection system 22
- 23. 1. CAPSULE ELEVATOR EQUIPMENT 2. CAPSULE FILLING EQUIPMENT 2.1 POWDER FILLING 2.2 GRANULE FILLING 2.3 PELLETE FILLING 2.4 TABLET FILLING 2.5 LIQUID FILLING 3. AIR DISPLACEMENT UNITS (ADU) 4. METAL DETECTION SYSTEM 5. DEDUSTING & POLISHING MACHINE 6. SORTER FOR DEFECTIVE CAPSULES 23
- 24. The FCE-100 is a high output elevator suitable for elevating from a lower level to higher level. This unit is extremely useful in fully automatic lines where the output from the exit chute of a filling/sorting machine, which is at a lower level, is connected to the inlet chute of a polishing machine which is at a higher level. Can convey all capsule sizes from 00 to5 Inbuilt blower unit GMP conforming design Out put: 1,00,000 capsules/hour 24
- 25. For more no. of filling machines see www.made-in-china.com www.fuchang.com More than hundereds of filling machines are there. 25
- 26. The AF-90T is a fully automatic capsule filling machine that can fill a large variety of powder formulations into hard gelatin capsules. A pellet filling / tablet filling / capsule in capsule device is available as an optional attachment. Output : Up to 90,000 capsules / hour for powder filling Up to 80,000 capsules /hour for pellet filling Up to 75,000 capsules /hour for tablet filling Conforming to cGMP Savings in manpower costs 26
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- 28. Output: 33,000 capsules per hou Self-contained horizontal hydraulic closing system which eliminates the need for compressed air . Internal vacuum pump TFR 8 Tablet Filling Ring for inserting tablets into capsules 28
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- 30. This machine can pack granular such as salt, sugar, medicine etc. 30
- 31. The ADU-100 is a dust extraction unit. It is used for collecting loose powder from the polishing chamber of the DP-100. It is also used for cleaning operations on automatic capsule filling machines. The unit removes loose powder, caps, bodies, and capsules lying around the machine. It can also be coupled with tableting machines for dust collection. 31
- 32. 100% online metal detection with automatic capsule filling machine The Metal Detection system works on the Eddy Current Principle using a focused electromagnetic field. Dual Channel Phase Sensitive systems are used. It detects all metals (Ferrous, non-ferrous / non-magnetic stainless steel). It detects very minute particles of stainless steel and metal flakes Inadvertently present in formulations All contact parts are manufactured with SS:318 as per GMP standards32
- 33. The DP-100 is an advanced de-dusting and polishing machine. More flexibility & higher degree of operating efficiency and cleanliness 1,20,000 capsules/hr 33
- 34. The Mini Capsule Sorter is specially designed for automatic sorting of loose caps, loose powder and diametrically defective filled capsules. It can directly be coupled with any automatic capsule filling machine. All contact parts are made of SS-316 and all aluminium parts are specially plated. Can sort capsules of sizes 000 to 5 34
- 35. (1) GENERAL REQUIREMENT: 1.1 The environment condition in which filling of hard gelatin capsule should be normally carried out is : Humidity :--------- Not more than 35% RH Temperature :--- Not more than 25 0C These conditions should be maintain even work has stopped at the end of working day and during the week- ends. 1.2 The area around machine should be kept clean at all times. The machine must be thoroughly cleaned during the week ends and when there is a product change –over. 35
- 36. 1.3 The speed gear should not be adjusted when the machine is running on power. 1.4 Operator should wear rubber gloves, nose mask and head covers when the machine is operated for filling. (2) PRELIMINARY OPERATIONS 2.1 The RH in the room or area should be checked and recorded on manufacturing sheet. Filling should not be started if humidity is more than 35%. 2.2 The compressed air supply should be turned on and regulator set at about 5 psi. 2.3 The vacuum pump should be turned on with vacuum hole blocked and the vacuum adjusted to not less than 600 mm Hg. 36
- 37. (3) LOADING AND RECTIFICATION 3.1 The setting of the loader and rectifier is checked by rotating the machine manually with the clutch in the “ON position” and the adjustments should be made. 3.2 The bag of empty capsule shells should be opened and with a clean scoop capsules should be loaded into the hopper of the rectification assembly. 3.3 The capsule holding ring should be placed on the turn –table and turned clock wise until it stops firmly against the drive pin. 37
- 38. 3.4 The machine should be run manually to check if the capsules enter the ring correctly. If not, the necessary adjustments should be made. 3.5 The main switch of the machine should be switched on and the vacuum pump started. The vacuum should not be less than 600 mmHg. 3.6 The machine should be started and the clutch lever moved to the right to bring the capsule loader into action. It should be checked whether the capsules are loaded properly. If the loading is satisfactory, the loading of the disc should be completed. 38
- 39. 3.7 The ring assembly should be subjected to two or three revolutions on the turn- table in an anti clockwise direction to provide the capsules additional exposure to vacuum for effective separation of the bodies from the caps. 3.8 The ring assembly should be removed from the table slowly taking care to avoid spilling the capsule; if then be placed on the ring of the machine. 3.9 If the loading and rectification of the capsules are satisfactory the process should be repeated with another ring assembly. 39
- 40. (4) FILLING OF POWDER 4.1 The operator should run his hand lightly over the ring to ensure that all the capsules are below the ring surface, 4.2 The speed of the turntable should be adjusted to the pre-determined rate. This should not be adjusted while the machine is running on power. 4.3 The drug hopper should be filled with the powder up to the stirring arm. 4.4 The machine should be switched on and the drug hopper pulled over the face of the moving ring until the stirrer start moving and the powder fills the capsule bodies. 40
- 41. 4.5 At the end of one revolution of the ring should be pushed back smartly in order to avoid double feeding of powder. 4.6 Excess powder from the surface of the ring should be scraped off with a teflon scraper and the powder should be collected in the dust tray. 4.7 The body ring with the capsules filled with powder should be removed and the cap ring placed on it and positioned so that the two rings are joined. (5) SEALING OF CAPSULES 5.1 The pressure of the compressed air supply should be checked and adjusted if necessary to between 5.5 kg/sq.cm to 6.5 kg/sq.cm. The air supply valve should be open. 41
- 42. DIMENSIONS (in millimeter) TABLE 1 OUTSIDE DIAMETER Size CAP (mm) BODY(mm) #0 7.57 - 7.69 7.26 - 7.38 #1 6.85 - 6.97 6.56 - 6.68 #2 6.28 - 6.40 6.01 - 6.13 TECHNICAL SPECIFICATIONS The various quality variants are controlled as per specification prescribed in I.P. 1996 for empty HGC shell. 42
- 43. TABLE 3 PRELOCK JOINED LENGTH OF EMPTY SHELLS Size Prelock Joined Length (mm) #0 23.92 24.92 #1 20.59 21.59 #2 19.02 20.02 TABLE 2 LENGTH Size CAP (mm) BODY(mm) #0 10.88 - 11.48 18.42 - 19.02 #1 9.71 - 10.31 16.42 - 17.02 #2 8.87 - 9.47 15.04 - 15.64 43
- 44. TABLE 5 WEIGHT OF CAPSULES (in milligram) & VOLUME (in CC) AVERAGE WEIGHT (Deviation ± 5%) & VOLUME (in CC) Size Average Weight (mg) (Avg. of 20 Capsules Taken Together) Volume (CC) #0 96 0.68 #1 76 0.50 #2 63 0.38 TABLE 4 WALL THICKNESS Size CAP (mm) BODY(mm) #0 0.190 - 0.210 0.183 - 0.203 #1 0.185 - 0.205 0.181 - 0.201 #2 0.180 - 0.200 0.180 - 0.200 44
- 45. TABLE 7 MOISTURE CONTENT AND DISINTEGRATION TIME MOISTURE CONTENT 13.0 % - 16.0 % DISSOLUTION TIME Less than 15 minutes. TABLE 6 MICROBIOLOGICAL LIMITS TOTAL COUNTS OF ORGANISM Less than 1000 / gm E COLI NIL (Absent) SALMONELLA NIL (Absent) TESTS AS PRESCRIBED BY I.P. 1996 45
- 46. A.PROCEDURE FOR PRODUCT TO PRODUCT CHANGE OVER Dedusting external surface – Use a clean nylon brush and vacuum cleaner. Dismantling- Remove A. Filling and Loading turn- tables B. pusher slide C. Rectifier, raceway with guide block D. Magazine E. Drug hopper, auger and stirrer F. Peg ring plate G. Partial fill attachment 46
- 47. Collect all these parts in a suitable SS container. CLEANING OF PARTS – clean the above parts by washing with 0.1%Teepol solution and scrubbing with soft clean nylon brush. Rinse with jet of potable water followed by rinsing with 5 micron filtered water. CLEANING OF CAPSULE PLATES- capsule plates are soaked in hot 5 micron filtered water for 5-10min. The holes are cleaned using 0.1% Teepol solution. Rinse with jet of potable water by dipping in 5 micron filtered water. CLEANING OF MACHINE BODY- clean with 0.1% Teepol solution and scrubbing with soft nylon brush. Clean with potable water. CONFORMING EFFECTIVENESS OF CLEANING- the water rinse of product hopper and capsule plates is sent to QC department to confirm absence of previous product. 47
- 48. Drying – the cleaned dried parts as mentioned in step 2 are wiped and dried using a clean lint free duster. The capsule plate has air-dried and stored in a SS trolley. Assembling – Resemble all the parts of machine carefully checking for correctness of assembling and free motion of moving parts. Replace the filter bag in the vacuum can below the machine with a clean filter bag. 48
- 49. RAW MATERIALTESTING GELATIN: BLOOM VISCOSITY MOISTURE PH ISO IONIC POINT,PH PARTICLE SIZE SO2 (PPM MAX) H2O2 CLARITY MICROBIAL STANDARDS FILL MATERIAL POWDER SEMI SOLID LIQUIDS-SUSPENSION, EMULSION, SOLUTIONS 49
- 50. I.p.Q.C. DURING FILLING WEIGHT VARIATION TEST MOISTURE CONTENT LOCK LENGTH FINAL PRODUcT Q.C. PHARMACOPOIEAL STANDRAD UNIFORMITY OF MASS UNIFORMITY OF CONTENT DISINTEGRATION TEST DISSOLUTION TEST MICROBIAL TEST INDUSTRIAL STANDRAD DIMENSION CAPSULE SHAPE SOLUBILITY ODOUR 50
- 51. INTRODUCTION PLANT LAY OUT MANUFACTURING PROCESS EQUIPMENTS STANDARD OPERATING PROCEDURE I.P.Q.C. FINAL PRODUCT Q.C 51
- 52. One piece, hermetically sealed soft gelatin shell containing a liquid, a suspension or semisolid. Filling volume from 0.1 ml to 20 ml. Available in different shapes like round oval, oblong, tube shaped and many more. 52
- 53. CHANGE ROOM(F) CHANGE ROOM(M) OFFICE DISPENSING MAT. STORE CORRIDORE UNCLEANED CONTAINER DRYING OFFICE SPARE SPARTS PACKAGING AREA BLISTER PACKING FILL CAPSULE STORE ROOM AIRLOCK AIRLOCK I.P.Q.C INTERMIDIATE STORE GELATIN PREPARATION MEDICAMENT PREPARATION ENCAPSULATION AREA WASHING ROOM SOLVENT STORE ROOM Two floor building first preparation of medicament and gelatin encapsulation room at ground floor 53
- 54. COMPOSITION OF SOFT GELATIN CAPSULE SHELL 1) GELATIN 2) WATER 3) PLASTICIZER GLYCERIN SORBITOL 4) PRESERVATIVES METHYL PARABEN PROPYL PARABEN 5) COLORANTS F.D & C CERTIFIED LAKES 6) OPACIFIER TITANIUM DIOXIDE 7) FLAVOURING AGENT ETHYL VANILLIN 8) ANTI TANNING AGENT FUMARIC ACID (AIDS TO SOLUBILITY) 54
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- 56. STEPS OF MANUFACTURING OF SOFT GELATIN CAPSULE SHELL 56
- 57. The Shell of the Soft Gelatin Capsules comprises of pure Pharmaceutical grade Gelatin, a plasticizer ( usually Glycerin ),and other ingredients. Gelatin Shell raw Materials are accurately weighed and then blended with demineralized water and melted under vacuum in large stainless steel pressure tanks. Completed batches are then transferred to the production lines in heat controlled receiving tanks in which the gelatin mass is maintained at the required temperature and viscosity. 57
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- 59. LIST OF METHODS 1) GLOBEX METHOD 2) ROTORY DIE METHOD 3) ACCOGEL METHOD 4) NORTON METHOD 5) COLTON METHOD 6) UPJOHN METHOD 7) PLATE METHOD 8) RECIPROCATING DIE METHOD 59
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- 63. Immediately after manufacture capsules are subjected to “naptha” wash to remove mineral oil form the outer surface of the capsule. Centrifuge is used for capsule washing Products are pre-shaped, semi dried in tumbler washer drier units. Tumbler drier unit having temp. <350C which removes all the solvent used in washing and 50 – 60% of water 63
- 64. CAPSULE DRYING TUNNEL SYSTEM is constructed from modular panels in stainless steel AISI 304. The tunnels have a laminar flow air filtration unit, which allows a better and more efficient drying of the capsule products. 64
- 65. 100% inspection is performed on the external appearance (Improper Sealing, Color, Soft spot & Seam continuity) Capsules are manually inspected for physical defects 65
- 66. Online Automatic Capsule Inspection Machine. Affordable 3 camera system 120,000 Capsules/hours INSPECAPS 150 66
- 67. Capsules are over-printed for logos or trade marks, if required. Products are strip packed, blister packed, bottle pack and bulk packed as required. 67
- 68. During encapsulation Seal thickness and ribbon thickness Uniformity of mass Disintegration time Fill matrix weight Temp. of gelatin tank Capsule shell weight Moisture content &soft gel hardness at the end of the drying stage 68
- 69. PHARMACOPIEAL STANDRAD ACTIVE INGREDIENT ASSAY RELATED INGREDIENT ASSAY UNIFORMITY OF MASS UNIFORMITY OF CONTENT DISSOLUTION TEST MICROBIAL TEST MOISTURE CONTENT DETERMINATION RUPTURE TEST INDUSTRIAL STANDRAD DIMENSION CAPSULE SHAPE SOLUBILITY ODOUR 69
- 70. The combination example consists of a high potency insoluble active in a lipid emulsion, sustained release tablet and a cocktail of two crystalline active materials. A combination of release profiles can be incorporated in the system.70
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- 76. Schedule M, Indian Government, 2003,1-43 Pharmaceutical capsules . Second edition Quality Assurance Guide vol. I& II first edition Dispensing For Pharmaceutical Students by Cooper and Gunn How to Practice GMPs by P.P.Sharma Pharmaceutical Process Validation by LOFTUS and NASH www.indianindustry.com www.fujicapsule.com/english/system/seam.htm http://pharmlabs.unc.edu/capsules/text.htm www.pharmagel.it/production2.htm www.drugdeliverytech.com www.capsugel.com www.innercaps.com www.intota.com/viewbio. 76
- 78. THANKS TO ALL 78