INNOVATION IN CAPSULE DOSAGE FORM

INNOVATION IN CAPSULE
DOSAGE FORM
LIST OF CONTENTS  Introduction
 Innovations
in capsules
1 . Innovation in capsule shells
2 . Innovation in capsule system
 Newer technologies
 Current research
 Reference
MAINLY TWO TYPES
1. HARD GELATIN CAPSULE
2. SOFT GELATIN CAPSULE
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
Capsules are use for filling different materials like
Powder
Tablets
Granules
Caplets
Beads
Pastes
INNOVATIONS IN
CAPSULES:

Innovations in Capsule Shells: it includes
modification of capsule shell to improve shell property.
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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.
1 INNOVATIONS IN CAPSULE
SHELLS:
IT INCLUDES:
Non animal Capsule
Capsule
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HPMC Capsules
Pullulan Capsules
Capsule(OceanCaps)
PVA Capsule
Starch Capsule
V Caps®
Animal
Gelatine/ PEG Capsules
Coni-Snap®
Press-fit® Gelcaps
LiCaps®
Posilock
Minicapsule
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
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.
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.

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, Glutenfree.
C. PVA CAPSULES:
Insoluble drugs can be dissolved in solvents such as
macrogol 400, being filled in capsules
.
The bioavailability of insoluble drugs can be improved
very much.
E.g. PONDAC Capsule (name)
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
Enteric starch Coating of starch capsules appear to be less problematic becoz of the
smooth seal, coupled with the higher bulk densityof 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, gluten-free and preservative-free
Easy to swallow
Effectively mask taste & odor
2. ANIMAL CAPSULE SHELL
A. Ocean CapsTM:

It contain all-natural marine supplements
Ideally suited for fish-eating vegetarians looking for fish
capsules, and marine supplements such as fish oil, DHA,
salmon liver oil, shark cartilage, glucosamine iron,zinc,
calcium and vitamins B2 and B12 .
B. PRESS FIT® GELCAPS:


consisting of a high-gloss gelatin coating that encases a
caplet core.
Manufactured by exclusive cold- shrink process
Press-fit gelcaps combine the best qualities of a gelatin
capsules with the density of a tablet, creating an exciting
new dosage form that can be custom engineered to meet
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.
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
 Minicapsule

dimensional specifications
Minicapsules are available in both gelatin and
hypromellose (HPMC) options.
25 mm3
CAPACITY
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
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

1. PORT CAPSULE TECHNOLOGY:
eg.Pseudoephedrine delayed release
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
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
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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

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.
•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.
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.
 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.
5. PULSIN CAP:
Used for pulsatile drug delivery.
consists of insoluble capsule body and a soluble capsule
cap.
6. GalacticlesTM

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 liquidfilled 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
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

Advantages of Orbexa
 Aqueous or solvent-based granulation
 High-speed process is well suited for sensitive
molecules like proteins
 Suitable for high drug loading
2. EURAND MINITABS® TECHNOLOGY:

Eurand's microencapsulated drugs can be tastemasked and directly compressed with Advatab to
ensure an optimised drug delivery process.
Microcaps® - microencapsulation of drug particles via
a proprietary coacervation technique for uniform,
precise taste-masking
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 12mm in diameter containing drug plus
excipients and coated with product specific
controlled release polymers.
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.
 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.
5. PRODAS® TECHNOLOGY:
which is unique in that it combines the benefits
of tabletting technology within a capsule.
 It can be used to pre-program the release rate of
a drug.

 PRODAS®
technology, by incorporating
minitablets with different release rates, can
display the characteristics of a number of
different conventional dosage forms:
 delayed release component for site/regional
release and/or food resistance
 sustained release component for additional
controlled release/profile extension
6. BANNER’S VERSETROLTM TECHNOLOGY:
 Drug
is incorporated in lipophilic or
hydrophilic matrix and that is than
incorporated in soft gelatin capsule shell.
7. Bijel Capsules: Co-release Micro-gel
new generic route to gel capsule formulation,
involving particles suspended in fluid-bicontinuous
mixture of two solvents.
 The bijel capsules are made of two fluids and hence
they are both a gel and an emulsion. The water and oil
domains inside the capsules can be used to deliver
chemically different active ingredients. The capsules
can be designed to release or mix the active
ingredients in response to a specific external stimulus.

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Chewable SGC require mixture of gelatin having
different bloom values.
Most preferable combination ration : 3:1 to 5:1
It contains ingredients like,


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Low bloom gelatin
Medium bloom gelatin
Placticizers
Water
Moisture retaining agent
Other
Jintan Capsule Mira
cell
Soft Capsule
Hard capsule
DROPPING METHOD
FILLER
ROTARY DIE PROCESS
DIPPING METHOD
10%~
30%~
20~50%
DIAMETER
0.3mm~10mm
5mm~20mm
10mm~21mm
CONTENT
LIPOPHILIC
HYDROPHILIC
POWDER
LIPOPHILIC
POWDER IN SUSPENSION
POWDER
SHELL
MATERIAL
GELATIN
AGAR
NATURAL GELLING
SUBSTANCE
GELATIN
GLYCERIN
GELATIN
GLYCERIN
SHELL
FUNCTION
HEAT RESISTANCE
ACID RESISTANCE
FREEZING RESISTANCE
NO FUNCTION
NO FUNCTION
CHARACTERI
STICS
FUNCTIONS CAN BE
ADDED TO THE SHELL.
POSSIBLE TO DESIGN
MULTIPLE LAYER
CAPSULES
SHELL THICKNESS IS
LARGE ENOUGH TO JOINT
TWO PCS OF GELATIN
SHEETS.
USE OF GLYCERIN CAN
CAUSE BLOCKING.
ONLY AVAILABLE FOR
POWDER, NOT
LIQUID AS CONTENT.
NO USE FOR SMALL
CAPSULES.
APPEARNCE
MANUFACTU
RING
SHELL
RATIO
Drugs and Dosage Forms Used for Oral Transmucosal
system
Drug
Brand Name Availability Formulation/
(Manufacturer)
Nifedipi
ne
Gel-filled
Capsule
Procardia
(Pratt)
Adalat
(Bayer)
10 and
20
mg/capsul
e
Dose/
Onset of
Duration of
Excipients
Directions Action (min) Action
Glycerin,
peppermint
oil, PEG,
soft
gelatin
capsule
Swallow
whole,
bite and
swallow,
or bite
and hold
sublingu
all
10
Approx 2
hr
EXAMPLES OF MARKETED PRODUCTS
Drug
Dosage form
Compound
Company
Indication
FORMULATIONS
Name
Neoral®
Cyclosporine
Soft gelatin Capsule
Novartis
Immune
Suppressant
Norvir®
Ritonavir
Soft gelatin capsule
Abbott
Laboratories
HIV antiviral
Fortovase®
Saquinavir
Soft gelatin capsule
Hoffmann-La
Roche
HIV antiviral
Agenerase®
Amprenavir
Soft gelatin capsule
Glaxo
Smithkline
HIV antiviral
Convulex®
Valproic acid
Hard gelatin Capsule
Ligand
Antiepileptic
Lipirex®
Fenofibrate
Soft gelatin capsule
Genus
Antihyperlipoprote
inemic
Sandimmune®
Cyclosporine
Soft gelatin capsule
Pharmacia
Immuno
Suppressant
CURRENT RESEARCH





Invitro – invivo evaluation of a novel capsule for colon specific drug
delivery (JPS Vol. 98 No. 08 Aug. 2009 Page no. 2626)
A novel approach to prepare insulin-loaded poly ( lactic –co-glycolic
acid microcapsule) (JPS Vol. 98 no.05 May 2009 page no.1712)
Effect of lipophilic compounds on the compatibility of lipid based
formulation with HG capsules. (JPS Vol. 99 no.01 Jan 2010 )
The Bilayer floating capsule : A stomach – directed drug delivery
system for misoprostol. ( Pharmaceutical research Vol. 9 No.3 1992)
Self micro emulsifying drug delivery system
(IJPS Vol-1, Issue-2, 2010)
Self micro emulsifying drug delivery systems are isotropic mixtures of oil,
surfactant, co-surfactant and drug with a unique ability to form fine oil in water
microemulsion upon mild agitation following dilution with aqueous phase.

Pulsatile delivery systems: An approach for
chronotherapeutic diseases (Year : 2010 | Volume : 1 | Issue :
1 | Page : 55-61)
Marketed technologies such as PULSYS™, CODAS® , TIMERx® , and
DIFFUCAPS® follow one of the above mechanisms to render a sigmoidal drug
release profile.

Novel iron- polysaccharide multilayered microcapsule for controlled insulin
release.
(C.A. vol. 150 no. 22, 2009 page no. 1469)

cholesterol mediated anchoring of enz. Loaded liposomes within disulfide
stabilized polymer carrier capsule. (C.A. vol. 150 no. 21 , 2009 page no. 1479)
achieved by non covalently sandwiched the liposomes b/w a tailor made cholesterol
modified poly(-lysine) precursor layer & a poly ( methacrylic acid) –co- (cholesteryl
methacrylate) capping layer.

COATING METHOD FOR SOFT GELATIN CAPSULES WITH
IMPROVED STABILITY .
(Ref: Chemical Abstracts, Vol 151, Number 13, September 28,2009 , Page2156,
297838p)

hydrocapsule : A new method for aqueous drug delivery.
(C.A. vol. 149 no. 2 2008 page no. 1479)

development of boron nanocapsule for neutron capture therapy.
(C.A. vol. 150 no. 22, 2009 page no. 1455)

Cross-linked DNA capsules templated on porous calcium
carbonate microparticles: (Colloids and Surfaces A: Physicochemical and
Engineering Aspects, Volume 356, Issues 1-3, 5 March 2010, Pages 126-133)
first, DNA was adsorbed onto calcium carbonate
microparticles, and then the adsorbed DNA was covalently crosslinked with each other by using ethylene glycol diglycidyl ether.
This method has the potential to be used for the preparation of
various single-component polymer capsules.
LIST OF REFERENCE
Chemical Abstracts, Vol 151, Number 13, September
28,2009 , Page no. 2156
 JPS Vol. 98 No. 08 Aug. 2009 Page no. 2626
 JPS Vol. 98 no.05 May 2009 page no.1712
 JPS Vol. 99 no.01 Jan 2010
 JPS Vol. 69 no.04 April 2007 page no. 479-488
 Pharmaceutical research Vol. 9 No.3 1992
 Angewandte Chemie International Edition Volume 49,
Issue 39, pages 6954–6973, September 17, 2010)
 IJPS Vol-1, Issue-2, 2010
 Drug development & delivery Issue Date: Vol. 2 No. 7
October 2002

Journal of Pharmaceutics and Cosmetology Vol 1: 2
(2011) page no 56-66
 Drug development & delivery Issue Date: Vol. 2 No. 7
October 2002
 www. morishita jintan co.ptd
 http://en.wikipedia.org/wiki/Encapsulation_(pharmacol
ogy)
 www.innercaps.com
 www.capsugel.com
 http://www.emisphere.com
 http://www.qualicaps.co.jp/
 http://www.capstech.com.cn
 C.A. vol. 150 no. 22, 2009 page no. 1469
 C.A. vol. 149 no. 2 2008
 C.A. vol. 150 no. 21 , 2009
