this presentation gives brief about introduction and innovation in capsule

1. INTRODUCTION TO
CAPSULE AND
INNOVATION IN CAPSULE
DOSAGE FORM
VIJAY GAJERA
M.PHARMA SEM III( PHARMACEUTICS)
L.M COLLEGE OF PHARMACY

2. LIST OF CONTENTS -
 Introduction
 Innovations in capsules
1 . Innovation in capsule shells
2 . Innovation in capsule system
 Newer technologies
 Reference
2

3. INTRODUCTION
• DEFINITION:-
These are solid dosage form of medicaments, in
which drug is enclosed in either a hard or soft
soluble container or shell made up of gelatin.
3

4. 4
MAINLY TWO TYPES
1. HARD GELATIN CAPSULE
2. SOFT GELATIN CAPSULE

5. 5
These capsules are made up of gelatin blends, small
amount of certified dyes, opaquants, plasticizers and
preservatives.
HARD GELATIN CAPSULE

6. 6
Certified Dyes
Colour approved by D & C act.
Opacifiers
Tio2
Plasticizers
Sorbitol, Glycerin.
Preservatives
Propyl and Methyl Parabens

7. PARTS OF CAPSULE
7
CAP
BODY

8. 8
MANUFACTURE OF EMPTY GELATIN
CAPSULES
Steps involved in making empty gelatin
capsules…
 Dipping
 Spinning
 Drying
 Stripping
 Trimming and Joining
 Polishing

9. 9

10. 10
Dipping :
Pairs of the stainless steel pins are dipped into the
dipping 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 are rotated to distribute the gelatin over the
pins uniformly and to avoid the formation of a bead
at the capsule ends.

11. 11
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 to
remove water
Stripping :
A series of bronze jaws strip the cap and body
portions of the capsules from the pins.

12. 12
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.

13. 13
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.
Storage
Finished capsules normally contain an equilibrium
moisture content of 13-16%.
To maintain a relative humidity of 40-60% when
handling and storing capsules

14. 14
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

15. 15
There are two basic types of gelatin
TYPE A
Derived from acid treated precursor that exhibits
an iso electric point at pH-9. It is manufactured
mainly from pork skin.
TYPE B
Derived from alkali treated precursor that
exhibits an iso electric point at pH-4.7. It is
manufactured mainly from animal bones

16. 16
SOFT GELATIN CAPSULE
Definition:-
Soft Gelatin capsules are one piece, hermetically sealed, 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.

17. 17
MANUFACTURE OF SOFT GELATIN
CAPSULES
Is manufactured by four methods
 Plate process
 Rotary die process
 Reciprocating die
 Accogel machine

18. 18
PLATE PROCESS:
•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.

19. 19
Rotary die process:
The material to be encapsulated flows by gravity. the
gelatin sheets are feed on rolls contain small orifice
lined up with the die pocket of the die roll.
Two plasticized gelatin ribbons are continuously and
simultaneously fed with the liquid or paste fill between
the rollers of the rotary die mechanism where the
capsule are simultaneously filled, shaped, hermetically
sealed and cut from the gelatin ribbon.
The sealing of the capsule is achieved by mechanical
pressure on the die rolls and the heating(37-40°C) of the
ribbons by the wedge.

20. 20
The rotary die process

21. 21
IMPORTANT SPECIFICATIONS OF
GELATIN
Bloom or gel strength: It is a measure of cohesive
strength of cross-linkage that occurs between
molecules and is proportion to the molecular
weight of gelatin.
Bloom is determined by measuring the weight in
grams required to move a plastic plunger of
0.5inches in diameter, 4mm into a gelatin that
has held at 10°C for 17 hrs.
The unit of bloom is grams and it is between 150-
250g

22. Viscosity: Is determined by viscometer at 60°C and
it is a measure of the molecular chain length.
Standard used: 25-45 mill poise.
Iron content: Iron is always present in raw gelatin,
and its concentration usually depends on the iron
content of the large quantities of water used in its
manufacture .
amount should not exceed 15ppm.
22

23. 23
SIZE OF CAPSULES
Size Volume in ml Size in mm
000 1.37 26.3
00 0.95 23.7
0 0.68 21.8
1 0.50 19.2
2 0.37 18.3
3 0.30 15.3
4 0.21 14.7
5 0.15 11.9

24. 24
SIZE OF CAPLUSE
*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.

25. 25
SHAPE OF CAPSULE
The shape of soft gelatin
capsule are round, oval,
oblong, tube.

26. 26
EVALUVATION OF CAPSULES
1. STABILITY TESTS.
a) Shell integrity test
b) Determination of shelf life
2.INVARIABILITY TESTS.
a ) Weight variation
b) Content uniformity
3. DISINTEGRATION TEST.
4. DISSOLUTION TEST.
5. MOISTURE PERMEATION TEST.

27. 1.STABILITY TESTS
 Stability tests for capsules are performed to know the
integrity of gelatin capsule shell ( but not to know the
stability of therapeutically active agent ) and for
determining the shelf life of capsules.
 The tests helps in improving the quality of contents of
capsule shell and for choosing the appropriate retail
package.
BEFORE ACTUALLY PERFORMING THE TEST
FOLLOWING FACT:
the capsule shell are to be stabilized to know
atmospheric condition with relative humidity about 20-
30 % and temperature about 21-24⁰c . 27

28. 28
A ) SHELL INTEGRITY TEST :
▪ This test is performed to find out the integrity of
capsule shell.
The standard capsule shells kept at the room
temperature 40 ⁰c and 80% RH becomes more soft
,sticky and swollen .
B) DETERMINATION OF SHELF LIFE :
Shelf life or the expiry date of packed capsules is
determined under normal storage conditions.

29. INVARIABILITY TESTS
The invariabilty in the medicaments packed in
the capsule shells can be determined by
performing the following tests :
a) Weight variation test
b) Content uniformity test
29

30. DISINTEGRATION TEST
 Disintegration test is a method to evaluate the rate
of disintegration of solid dosage forms .
disintegration is defined as the breakdown of solid
dosage form into small particles after it is ingested .
30

31. DISSOLUTION TEST
▪ Dissolution test is an official method to
determine the dissolution rate of a solid dosage
form .
▪ Dissolution rate is defined as the rate at which the
drug is released into the systemic circulation from
the dosage from .
31

32. DISSOLUTION TEST APPARATUS
32
a) . Apparatus -1 ( rotating basket dissolution
apparatus ) :-
▪Small wire mesh size basket – 22
▪Temperature – 37 +/- 5⁰c
▪Rotated speed – 25 -150 rpm
▪Dissolution medium height from the
bottam of the vessel :- 23-27 mm

33. 33
b) Apparatus -2 ( rotating paddle dissolution
apparatus) :-
Small wire mesh size :- 22
Dissolution medium hight from the
bottam of the vessel :- 23-27 mm
▪Temperature – 37 +/- 5⁰c
▪Rotated speed – 25 -150 rpm

34. MOISTURE PERMEATION TEST
To assure the suitability of containers for
packaging capsules .
The moisture permeating feature of capsules
packaged in
▪ single unit containers – blister pack or strip pack
▪ unit dose containers – glass or plastic bottles
Are to be determined .
34

35. Some of the innovations are targeted to:
 Overcome the disadvantages associated with
conventional capsules.
 Achieve modified drug release.
 Encapsulation of various kind of material.
 Modified applications
35

36. Capsules are use for filling different materials like
Powder Granules Beads
PastesCapletsTablets 36

37. INNOVATIONS IN CAPSULES:
 Innovations in Capsule Shells: it includes
modification of capsule shell to improve shell
property.
 Improvement in the shell property
 Provide physical strength
 Protection from moisture
 Protection from microbial contamination
 Protection from light and oxygen
 Improve compatibility of fill material with capsule shell
 Innovations in Capsule System: it includes modification
of the system to achieve modified release.
37

38. 1--INNOVATIONS IN CAPSULE
SHELLS:
IT INCLUDES:
Non animal Capsule Animal Capsule
 HPMC Capsules Gelatine/ PEG Capsules
 Pullulan Capsules Coni-Snap®
 PVA Capsule Press-fit® Gelcaps
 Starch Capsule LiCaps®
 V Caps® Posilock
Minicapsule
OceanCaps
38

39. 1. NON-ANIMAL CAPSULE SHELL
A. HPMC CAPSULES(HYPROMELLOSE):
Hypromellose as a release controlling polymer with diffusion
and erosion controlled release
Features :
• Chemically stable.
• Low moisture content than Gelatin capsule, Less brittle
• Fast dissolution
• Lower water vapor permeability than Gelatin capsule.
(Gelatin>PEG-Gelatin>HPMC)
• High tolerance to temperature
• Chemical inactivity
39

40. QUALI-V®-I: A New Key for Dry Powder Inhalers
 Superior physical performance a moisture
content.
 Content could easily arises in the usage of DPI
with capsules.
 Better cutting & puncturing performance.
 Elimination of the generation of shell particles in
use.
40

41. 41

42. 42

43. B. PULLULAN CAPSULES
 Pullulan is a neutral glucan
 like Amylose, Dextran, Cellulose
 Water-soluble polysaccharide
• Derived by bacterial fermentation from corn.
• odorless, tasteless, and completely biodegradable .
• Dried capsules are comparatively weak in physical
strength
• Requires water to act as a film plasticizer, which may have
a negative effect on active ingredients.
43

44. NP CAPSTM:
 Made up of pullalan.
 Pullulan is very stable and well-characterized, and
has achieved wide regulatory acceptance with its
proven safety record.
 No chemical modification,
 Starch-free
 Preservative-free
44

45. C. PVA CAPSULES:
 Insoluble drugs can be dissolved in solvents such as
macrogol400, being filled in capsules.
 The bioavailability of insoluble drugs can be improved
very much.
 E.g. PONDAC Capsule (name)
45

46. D. STARCH CAPSULES:
 Manufactured by the injection moulding technique
developed by Capsugel (Capill®).
 Sealing is achieved by applying a hydro alcoholic
solution to inner section of the cap, immediately prior
to its being placed on to the body.
Offers advantages like.
 pH independent dissolution
 Suitable for enteric coating
 Tamper evident
46

47. Enteric starch -
 Coating of starch capsules appear to be less
problematic becoz of the smooth seal, coupled with the
higher bulk density of the capsules, which provides for
s more uniform coating bed.
 VCaps®:
 Two-piece capsules made from cellulosic raw materials
 Vcaps capsules are also starch-free, and
preservative-free
 Easy to swallow
 Effectively mask taste & odor
47

48. 2. ANIMAL CAPSULE SHELL
A. Ocean Caps TM:
o It contain all-natural marine supplements
o Ideally suited for fish-eating vegetarians looking For fish
capsules, and marine supplements such as fish oil, salmon
liver oil, shark cartilage, glucosamine iron, zinc, calcium and
vitamins B2 and B12 .
48

49. C. LICAPS®:
 specially designed to be sealed for secure containment of liquids
and semi-solids.
 They may be filled at temperatures up to 70° C.
D. POSILOK®:
 The locking system used by Qualicaps.
 It ensures that the contents reach the consumer intact, and are
protected at all times from external contamination.
49

50. E. GELATIN/PEG CAPSULES:
 Reduce the brittleness of standard gelatin capsules when
exposed to a low-moisture content thus making the
capsules more compatible to hygroscopic formulations or
moisture-sensitive ingredients
 At moisture content b/w 8-12 %, gelatin / PEG capsules
have equivalent mechanical strength to standard
capsules with moisture b/w 13-16 %.
Gelatin/PEG Features
 Less brittle
 Good for hygroscopic formulations
 Good for moisture-sensitive ingredients
 Odorless, tasteless
 Three-year shelf life 50

51. MINI CAPSULE
 Minicapsule dimensional specifications
 Minicapsules are available in both gelatin and
hypromellose (HPMC) options.
CAPACITY
25 mm3
CAP LENGTH 4.3 mm +/- 0.30 mm
BODY LENGTH 7.3 mm +/- 0.30 mm
CAP DIAMETER 2.65 mm +/- 0.10 mm
BODY DIAMETER 2.40 mm +/- 0.10 mm
CLOSED JOINED
LENGTH
8.40 mm +/- 0.30 mm
WEIGHT 9.5 mg +/- 2 mg 51

52. INNOVATIONS IN CAPSULE SYSTEM:
To provide modified release :
 PORT CAPSULE TECHNOLOGY:
 HYDROPHILIC SANDWICH (HS) CAPSULE
 L-OROS®
 PULSINCAP
 CHEWABLE SOFT GELATIN CAPSULE
ENCAPSULATING LIQUID FILL
 INNERCAP TECHNOLOGY
 GALACTICLES
52

53. 1. PORT CAPSULE TECHNOLOGY:
eg.Pseudoephedrine delayed release
53

54. 54

55. 2 . HYDROPHILIC SANDWHICH(HS) CAPSULES:
 time delayed probe capsule , This effectively created a “ Hydrophilic
Sandwich “ between two gelatin capsule .
 When the outer capsule dissolved, the sandwich of HPMC formed a
gel barrier layer that provided a time delay before fluid could enter the
inner capsule and cause drug release
55

56. 3. L-OROS®:
Controlled Release of Non-Aqueous Liquid Formulation
 L-OROS Hard cap
 L-OROS Soft cap
 Delayed liquid bolus delivery system
consists of liquid drug, an osmotic engine or push layer and
a semi permeable membrane coating
 Enhanced bioavailability of class II drugs
 Uniform blood levels over specific period of time
 Reduced first pass effect
 Reduced dose
 Patient compliance
 Made of pharmaceutical acceptable excipient
56

57.  1.L-OROS HARD CAP:
The drug layer and the osmotic engine are encased in hard capsule which is
surrounded by the rate controlling semi permeable membrane.
A barrier layer composed of an inert substance separates the drug layer from
osmotic engine.
A delivery orifice is laser drilled at the opposite end of the osmotic engine providing
an outlet for the drug.
57

58. •The liquid drug formulation is encased in soft capsule. It is in turn surrounded by a
barrier layer, osmotic engine, and a semi permeable membrane in order.
•A delivery orifice in drilled through semi-permeable membrane,osmotic engine and
barrier layer. 58

59. DELAYED LIQUID BOLUS SYSTEM:
Delivers the pulse of the liquid drug.
The system consists of the placebo delay layer, a liquid
drug layer, an osmotic engine all encased by a subcoat
and then surrounded by semi-permeable membrane.
59

60.  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.60

61. 5. PULSIN CAP:
Used for pulsatile drug delivery.
consists of insoluble capsule body and a soluble capsule
cap.
61

62.  GalacticlesTM Oral Lipid Matrix in Liquid-Filled Softgel Capsules: A Novel
Drug Delivery System for Improved Oral Bioavailability & improve the
formulation of poorly soluble drugs, administered in liquid-filled softgel
capsules.
(Drug development & delivery Issue Date: Vol. 2 No. 7 October 2002)
50% neutral lipids (mono-, di-, and tri-glycerides), and 50% polar lipids
(mixed galactolipids and phospholipids, 70:30) called galactolecithin
6. GalacticlesTM
62

63. NEWER TECHNOLOGIES :
1. ORBEXA® TECHNOLOGY:
 It produces beads that are of controlled size and density
and suitable for formulation as controlled release
multiparticulates - using granulation, spheronization and
extrusion technique.
 The resultant beads can be coated with functional
polymer membrane for additional release rate control and
may be filled into capsules
63

64. Advantages of Orbexa
 Aqueous or solvent-based granulation
 High-speed process is well suited for sensitive
molecules like proteins
 Suitable for high drug loading
64

65. 2. EURAND MINITABS® TECHNOLOGY:
 Eurand's microencapsulated drugs can be taste-masked
and directly compressed with Advatage to ensure an
optimised drug delivery process.
Microcaps® - microencapsulation of drug particles via a
proprietary coacervation technique for uniform, precise
taste-masking
65

66. 3. SODAS® TECHNOLOGY:
 SODAS® (Spheroidal Oral Drug Absorption
System) is particulate drug delivery system.
 SODAS® Technology is based on the
production of uniform spherical beads of 1-2mm
in diameter containing drug plus excipients and
coated with product specific controlled release
polymers. 66

67. 4. CODAS® TECHNOLOGY:
 Chronotherapeutic Oral Drug Absorption
System(CODASTM Technology) was developed to
achieve this prolonged interval.
 Delay is introduced by the level of release
controlling polymer applied to the drug loaded
beads. The release controlling polymer is a
combination of water soluble and water insoluble
polymers.
67

68.  As water from the GIT contacts the polymer coat
beads, the water soluble polymer slowly
dissolves and the drug diffuses through the
resulting pores in the coating.
 The water insoluble polymer continues to act as
a barrier, maintaining the controlled release of
the drug.
68

69.  Chewable SGC require mixture of gelatin having
different bloom values.
 Most preferable combination ration : 3:1 to 5:1
 It contains ingredients like
 Low bloom gelatin
 Medium bloom gelatin
 Placticizers
 Water
 Moisture retaining agent
 Other
CHEWABLE SOFT GELATIN CAPSULE
ENCAPSULATING LIQUID FILL
69

70. REFERENCES:
 www.capsugel.com
 www.capsuline.com
 www.qualicaps.com
 www.banpharm.com
 A REVIEW ON RECENT INNOVATIONS IN CAPSULE
DOSAGE FORM, R D Doshi*, P L Patel , M R Patel , K
R Patel , N M Patel, INTERNATIONAL JOURNAL OF
DRUG FORMULATION AND RESEARCH, volume
2/Issue 3, May-June 2011, page no.77-92
 RECENT ADVANCES IN ORAL PULSATILE DRUG
DELIVERY
 ANANTHA NAYAKI RAVULA*, BAIRI AGAIAH GOUD,
Journal of Advanced Pharmaceutical
Sciences,Vol.1/Issue 1/2011, page no. 57-62
70

71. THANK YOU
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