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.

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

7. 7

8. PREPARATION OF GELATIN
8

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

20. • Farmetic
2000/15---40,000cap/hr
2000/30---80,000cap/hr
2000/60---1,60,000cap/hr
20

21. 21

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

27. 27

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

29. 29

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

55. 55

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

58. 58

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

60. 60

61. 61

62. 62

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

71. 71

72. 72

73. 73

74. 74

75. 75

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

77. www.eravat.com
www.safrroy.com
www.made-in-china.com
77

78. THANKS
TO ALL
78