HPMC capsule is superior to hard gelatin capsules in terms of mechanical strength, hygroscopicity and compatibility with a wide range of drugs. It exhibits better short term stability at high temperature conditions and remains flexible even at low moisture content. Two important areas where improvements have to be achieved in order to qualify the HPMC capsules ahead of Gelatin capsules are in their machineability and in the in vitro and in vivo disintegration/dissolution performances.

1. Presented By: DHRUTI AVLANI
B.Pharm, 4th year, 7th semester
Registration No.: 122770210011
Roll No.: 27701912011
NSHM Knowledge Campus, Kolkata –
Group of Institutions
GUIDE: Dr.Sutapa Biswas Majee

2. Capsules are solid dosage forms in which one or more medicinal and inert
ingredients are enclosed in a small shell or container usually made of
gelatin.
The concentrated solutions which require previous dilution are unsuitable
for capsules because if administered as such lead to irritation of
stomach.
1) Hard (two piece) Capsule 2)Soft (one piece) Capsule
 Mask the taste and odour of unpleasant drugs.
 Attractive in appearance, easy administration, economical.
 Shells are physiologically inert and quickly digested in the
gastrointestinal tract.
 Shells can be opacified (with titanium dioxide) or coloured, to give
protection from light.

3. Non - toxic
Soluble in hot water and sets to form a gel on
cooling
Good film-forming material, producing a strong
flexible film
The gelatin films are homogeneous in structure,
which gives them strength
Readily soluble in biological fluids at body
temperature

4. CROSS -
LINKING
• Causes -
• Excipients
undergo auto
oxidation.
• High
temperature
and humidity.
• Water soluble
proteins,
example
lysine.
MOISTURE
SENSITIVITY
• Moisture
content <12%,
hygroscopic
formulation –
gelatin film
becomes
brittle.
• Moisture
content >18% -
gelatin film
becomes soft.
RELIGIOUS
• Animal source
of gelatin can
be a problem
for certain
consumers
such as
vegetarians,
religious or
ethnic groups.
OTHERS
• Maillard
reaction –
discolouration
of the capsule.
• Special
packaging and
storage
conditions to
ensure
product
stability.

5.  HPMC stands for Hydroxypropyl Methyl Cellulose.
 Also known as Hypromellose.
 It is a methyl and hydroxypropyl mixed ether of cellulose.
 It is a natural polysaccharide found in all plant parts mainly wood.
 White to slightly off white powder or granules .
 It is a semisynthetic, inert polymer.
 It is insoluble in hot water, acetone and chloroform.
 It is soluble in cold water giving a colloidal solution owing to the
reversible thermal gelation property.

6. GELATIN HPMC

7. Mixing Of Raw
Materials
Dipping Drying
Coating/Banding
And Polishing
Capsule Filling
Positioning And
Stripping
NO Stringent
Gelation Conditions

8. QUALI-V®
Shionogi
Qualicaps
Carrageenan
Gelling Agent
Moisture
Content: 4-6%
Vcaps®
Capsugel
Gelling Gum
Moisture
Content: 5-6%
Vcaps Plus®
Capsugel
No Gelling
Agent
Moisture
Content: 4-5%

9.  Inspite of gelatin being the most widely used capsule shell
material, it has various disadvantages (animal source, cross-linking
property, moisture sensitive) and an alternative was required to
overcome the problems. So, HPMC has been considered as a good
alternative to gelatin.
 The main area where HPMC capsules can have better prospect
compared to gelatin capsules is in wider patients’ preferences since
it is not derived from animal source (skin or bones). It does not
show any cross linking property and is highly stable at different
conditions.
 The use of HPMC as an alternative to gelatin as capsule shell
material can only be confirmed by analysing and comparing the
quality control parameters of the empty and filled HPMC vs Hard
Gelatin capsules. (literature data)

10. PHYSICOMECHANICAL
PARAMETERS
• Capsule Dimensions
• Scanning Electron Microscopy
• Mechanical Strength
• Weight Variation
• Transport Simulation Test
IN-VITRO TESTS
• Formaldehyde Challenge
Test
• In-vitro Disintegration &
Dissolution Test
IN-VIVO TESTS
• Oesophageal Sticking
Tendency
• In-vivo Disintegration &
Dissolution Test
• Animal Data
• Human Bioavailability
INVITRO – INVIVO
CORRELATION AND
STABILITY STUDIES
CAPSULE SHELL EVALUATION

11. 2) SCANNING ELECTRON MICROSCOPY
Clean edge with a very smooth
surface - no leakage and better
disintegration studies
Rough edge with a smooth surface- no
leakage
1) CAPSULE DIMENSION
Slightly more gap between body and
cap- ↑ rejection rate due to leakage
Very little gap between body and cap-
almost no leakage
PARAMETER
HPMC CAPSULE SHELL GELATIN CAPSULE SHELL

12. 5) TRANSPORT SIMULATION TEST
No leakage No leakage
4) WEIGHT VARIATION
It is not significant in both the cases, therefore low rejection rate
3) MECHANICAL STRENGTH
At low humidity- maintain elasticity
and resist breakage. [2-7%
moisture content at 10-60% RH]
At low humidity- become brittle and
exhibit higher breakage rates. [13-
16% moisture content at 35-65% RH]
PARAMETER
HPMC CAPSULE SHELL GELATIN CAPSULE SHELL

13. Capsules were filled with lactose spiked with formaldehyde at 25 ppm
Capsules were emptied and filled with acetaminophen at a fill weight 380 mg
(±10 mg)
The capsules were tested as per the acetaminophen capsules USP monograph
for Acetaminophen Capsules – Dissolution Test with water and USP apparatus
II (paddle, 50 rpm)
After 1 week storage at room temperature, dissolution of acetaminophen from
the HPMC shell is unchanged while gelatin shell observed significant dissolution
slow down
1 week storage in HDPE
bottles at room temperature
Cross-linking susceptibility of
capsules is assessed by comparing
the dissolution results.

14. HPMC is a
bioadhesive
material
Therefore it is expected
that an increase in the
oesophageal residence time
would occur before reaching
stomach.
Both HPMC and Gelatin capsules are
administered simultaneously with 180 ml
water to eight healthy male subjects
following an overnight fast.
No
prolonged
oesophag-
eal hold-
ups,even
for HPMC
capsules
To avoid oesophagus
entrapment of solid dosage
forms, they should be taken
in upright body position with
at least 50 mL of water to
minimize entrapment
INFERENCE
METHOD
PRINCIPLE

15. IN-VIVO
STUDIES
PRINCIPLE:
Capsules radiolabled
with indium-111, filled
with a plug of lactose-
based formulation and
administered
simultaneously to each
individual with 180 ml
of water.
RESULT:
HPMC Capsule – 9 mins
Gelatin Capsule – 7 mins
INFERENCE:
Due to this minimal
difference, HPMC
is considered as an
alternative to
Gelatin capsules.

16. PARAMETERS ANIMAL DATA HUMAN DATA
SPECIES Dog (4 male dogs) Humans (6 human beings)
CONDITIONS Overnight fast and fed state Overnight fast and fed state
PARAMETER Tmax Tmax
PRINCIPLE
METHOD
Blood samples were drawn up to
24 or 30 h after dosing; plasma
was separated, analyzed for
drug content and validated by
mass spectroscopy.
Blood samples were collected
up to 72 h post-dose, plasma
separated and analyzed for
drug content with a validated
by mass spectroscopy.
RESULTS for
immediate
release
formulations
• HPMC capsules reflected a
rapid Tmax, indicating that the
dissolution of the capsule shell
was not rate-limiting for
absorption.
• Short Tmax reflects rapid in
vivo dissolution of HPMC
capsules.
• The median Tmax of ~1h in
fast state reflects the rapid
disintegration of the HPMC
capsule shell.
• Thus, HPMC capsules yield a
quick in-vivo plasma profile
for humans.

17. • HPMC: No change in dissolution of the
compound from capsule shell
• GELATIN: Significant slow down in dissolution
takes place
1) FORMALDEHYDE
CHALLENGE
TEST
• HPMC: Slow, but does not cause any delay in
drug absorption
• GELATIN: Fast
2) IN-VITRO
DISINTEGRATION
& DISSOLUTION
• No sticking tendency for both the capsule shells
• To avoid oesophagus entrapment of solid dosage
forms, must be taken in upright body position
with water to minimize entrapment
3) OESOPHAGEAL
STICKING
TENDENCY

18. • HPMC: 9 mins ; GELATIN: 7 mins
• Due to this minimal difference, HPMC is
considered as an alternative to Gelatin
capsules.
4) IN-VIVO
DISINTEGRATION
& DISSOLUTION
• HPMC: Rapid Tmax indicates dissolution of the
capsule shell was not rate-limiting for
absorption whereas short Tmax reflects rapid
in vivo dissolution of HPMC capsules.
5) ANIMAL
DATA
• HPMC: The median Tmax of ~1h in fast state
reflects rapid disintegration of the HPMC
capsule shell. Therefore they yield a quick
invivo plasma profile for humans.
6) HUMAN
BIOAVAILABILITY

19. VISUAL
EVALUATION
HPMC SHELL :
• No change upto
40°C
• Deformed at 70°C
GELATIN SHELL:
• No change upto
50°C
• Deformed at 60°C
DISINTEGRATION
DISSOLUTION
HPMC SHELL:
• No change upto
90°C
GELATIN SHELL:
• No change upto
60°C
• Deformed at 60°C
MECHANICAL
STRENGTH
HPMC SHELL:
• No change upto
90°C
GELATIN SHELL:
• No change upto
60°C
• Deformed at 60°C
HPMC capsules (200 capsules) were filled into glass bottles and heated
at different temperatures (up to 90 °C) for 24 h in an oven. The glass
bottles are kept at room temperature for at least 5 h before opening
and the capsules were evaluated on these parameters.

20. PARAMETERS HPMC CAPSULE GELATIN CAPSULE
Scanning
Electron
Microscopy
Clean edge with a very
smooth surface - no leakage,
better disintegration studies
Rough edge with a smooth
surface- no leakage
Mechanical
Strength
At low humidity- maintain
elasticity and resist
breakage. [2-7% moisture
content at 10-60% RH]
At low humidity- become
brittle and exhibit higher
breakage rates. [13-16%
moisture content at 35-
65% RH]
Weight Variation Not significant, therefore low
rejection rate
Not significant, therefore
low rejection rate
Transport
Simulation Test
No leakage No leakage

21. PARAMETERS HPMC CAPSULE GELATIN CAPSULE
Formaldehyde
Challenge Test
No change in dissolution of the compound
from capsule shell
Significant slow down in
dissolution takes place
In-vitro & In-vivo
Disintegration &
Dissolution Test
Slow, but does not cause any delay in drug
absorption
Dissolution Time: 9 minutes
Fast
Dissolution Time: 7
minutes
Oesophageal
Sticking Tendency
No sticking tendency No sticking tendency
Animal Data Rapid Tmax indicates dissolution of the
capsule shell was not rate-limiting for
absorption whereas short Tmax reflects
rapid in vivo dissolution of capsules.
-
Human
Bioavailability
The median Tmax of ~1h in fast state
reflects rapid disintegration of the HPMC
capsule shell. Therefore they yield a quick
invivo plasma profile for humans.
-
Stability Studies Stable upto 90°C Stable upto 60°C

22.  HPMC capsule is superior to hard gelatin capsules in terms of
mechanical strength, hygroscopicity and compatibility with a
wide range of drugs. It exhibits better short term stability at high
temperature conditions and remains flexible even at low moisture
content.
 Water in HPMC shell walls does not act as a plasticizer. Thus if
they lose water when they are exposed to low humidities during
storage or if the formulation filled in to them is hygroscopic then
they do not become brittle.
 Two important areas where improvements have to be achieved in
order to qualify the HPMC capsules ahead of Gelatin capsules are in
their machineability and in the in vitro and in vivo
disintegration/dissolution performances.

23. Oxygen penetration through shell walls is about 3 fold slower
for Gelatin than HPMC capsule. to put this into perspective it
must be remembered that the bulk of the oxygen will enter the
capsule through the gap between the cap and the body.
Band-sealing of HPMC capsules can reduce the
amount penetrating into the capsule. An anti-oxidant
can also be included in the formulation.
Pullulan is a natural water-soluble high
molecular polysaccharide produced from
starch. It exhibits low oxygen transmission
and extended shelf life. Eg: NPcaps

24. 1) Khar Roop K., Vyas SP, Ahmad Farhan J., Jain Gaurav K. (Eds),
Capsules in Lachman/Lieberman’s The Theory and Practice of
Industrial Pharmacy, 4th Edition, CBS Publishers & Distributors
Pvt. Ltd., New Delhi, 546 – 578.
2) Moawia M. Al-Tabakha, HPMC Capsules: Current status and
future prospects, J Pharm Pharmaceut Sci, 2010, 13, 428 – 442.
3) Rabadiya Bhavisha, Rabadiya Paresh, A Review: Capsule shell
material from gelatin to non animal origin material, International
Journal Of Pharmaceutical Research And Bio-Science, 2013, 2, 42-
71.
4) Stegemann Sven, Hard Gelatin Capsules today – and tomorrow,
Capsugel, 2nd edition, 2002, 1-23, http://www.capsugel.com
(accessed as on July 7, 2015)