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Table of Contents

General Product Characteristics

Properties of base Polymers


Capsule Composition
Gelling Mechanism
Capsule Properties
Appearance
Hygroscopicity
Mechanical Properties
Oxygen Permeability
Disintegration
Chemical Stability

HGC vs Vcaps vs NPcaps: What are the Differences?


Gelatin
Capsules

Hypromellose
Vcaps

Pullulan
Npcaps

Functional Characteristics
Moisture Content
Dimensions

14%

6%

12%

WW Specification

WW Specification

WW Specification

Sizes
Cross Link
Susceptible to Maillard Reaction
Gelling Agent
Gelling Promoter
Machineability
In Vitro Disintegration*
In Vivo Disintegration*
Oxygen Barrier Properties*

All

00 - 4

00 - 5

Yes

No

No

Yes

No

No

Self Gelling

Gellum Gum

Carageenan

None

Potassium Acetate

Potasium Chloride

Excellent

Good

Excellent

2.18

2.54

1.46

28

Excellent

Poor

Best

Extensive

Limited

Will be Extensive

Glass-Like

Natural Looking

Glass-Like

No?

Yes

Yes

Limited Locations

Yes

Yes

Limited Locations

Yes

Yes

No

Yes

No

No

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

No

Limited

Yes

Difficult

Yes

No Experience

No

Yes

Yes

Approx. 5 sec

Approx. 12 sec

Approx. 4 sec

Extensive

Extensive

Extensive

Appearance
Colour Pallet
Appearance
Certifications
Non-GMO
Halal
Kosher-KO
Kosher-OU
Non-Animal
GRAS Status
Gluten Free
Starch Free
Preservative Free
Non- Animal Approval Japan
General
Manufacturing Locations
Enteric Coat
Cold Water Soluble
Oesophageal Transit Time
Excipient Compatability

General Product Characteristics

Gelatin
Hypromellose =

Vcaps

Pullulan

NPcaps

Gelatin

Gelatin is a mixture of purified protein fractions consisting of


amino acids joined by amide linkages to form linear polymers.
Composition of bovine bone gelatin Source: Collagen from animal bones or skin
(values are given as numbers of residues per 1000 total residues)
Alanine
Glycine
Valine
Leucine

116.6
335
21.9
24.3

Isoleucine
Proline
Phenylalanine
Tyrosine
Serine
Threonine
Cystine
Methionine
Arginine
Histidine
Lysine
Aspartic acid
Glutamic acid
Hydroxyproline
Hydoxylysine

10.8
124.2
14.0
1.2
32.8
18.3
3.9
48.0
4.2
27.6
46.7
72.6
93.3
4.3

Amino acids have a two carbon bond.


One of the carbons is a part of a group
called the CARBOXYL GROUP. A
carboxyl group is made up of one
carbon, two oxygens and one
hydrogen atom. The carboxyl group is
acidic. The second carbon is a part of
the AMINO GROUP.
Amino means there is an NH2 group bonded to the carbon atom.
In the image you see a "+" and a "-". Those are there because in
Amino Acids one hydrogen atom moves to the other end of the
molecule. An extra "H" gives you a positive charge.

Hypromellose
Partly methylated and hydroxypropylated cellulose,
varying in MW from 10 000 to 1 500 000.

Source: Wood pulp

Where R is H, CH3 or CH3 CH(OH) CH2


Only self gelling at temperature 60C

Pullulan

Pullulan is an extracellular bacterial polysaccharide

Maltotriose:

Maltose:

Source:

Produced using a fermentation process


from corn starch by
Aureobasidium pullulans

Pullulan production
Corn syrup; certified Non- GMO
Nutrient
Microorganism

Fermentation

Filtration

Concentration

Pullulan

White dry powder


Aureobasidium pullulans
Abundant in nature (decaying trees, exterior
windows, breweries, paper mills, etc.)
Non-toxic
Non-pathogenic

Properties of Base Polymers


Solubility

Gel
Forming

Equilibriu
m
Moisture
Content at
50% RH

Practically
odorless and
tasteless slightly
yellow colored
powder

Insoluble in
cold water.
Soluble in
hot water.

Cooling <
40C of a
soln. above
a min.
critical
conc.

~ 14%

Hypromello
se
10 - 1500
(Vcaps)

Odorless and
tasteless, white or
creamy-white
powder

Soluble in
cold water

Thermo
gelling ~
60C

~ 6%

Pullulan
(NPcaps)

Odorless and
tasteless, white
powder

Soluble in
cold water

No

~ 12%

Polymer

Gelatin

M.W. 103

15 - 250

10 - 400

Description

Capsule Composition
Component

Gelatin

Vcaps

NPcaps

Polymer

Gelatin

Hypromellose

Pullulan

Gelling agent

Self gelling

Gellan gum

Carrageenan

Gelling promoter

None

Potassium acetate

Potassium
chloride

Capsule Properties
Gelatin capsules
Dissolution behaviour similar for all suppliers
Non-gelatin capsules
Dissolution properties dictated by the gelling agent
(gellan or carrageenan). i.e. Shionogis Quali-V will have
similar dissolution properties to NPcaps as both contain
carrageenan as gelling agent.

Capsule Properties
Other capsule properties, i.e.
hygroscopicity, mechanical properties,
permeability depend on the properties
of the base polymer.

Appearance
Gelatin

Vcaps

Smooth
Rough surface
surface
Natural look
High degree of
transparency
High gloss

NPcaps

Smooth surface
High degree of
transparency
High gloss

Hygroscopicity

Moisture Content & Mechanical


Properties
Customer Relevance

Moisture in shell can influence drug stability (eg aspirin).

Advantage of HPMC (limited no. of drugs in this category).

HPMC advantage in low dose inhalation drugs.

Fill material can influence capsule properties if fill is hygroscopic capsule moisture content could decrease with tendency to brittleness.

Capsule storage conditions for NPcaps will be important.

Final package requirements may not be the same as for gelatin.

Oxygen Permeability
Permeability test performed based on
oxygen transmission rate test
Standard ASTM D-3985 Unit cm 3/m2/day for 100 m film thickness

Oxygen Permeability
Capsules with wheat germ oil stored at 22C/50% for 3 months.

Peroxide
value

Oxygen Permeability
Csutomer Relevance?

Oxygen sensitive contents could degrade and


become rancid.
Extremely critical for liquids where interaction
between shell and content is intimate.

Disintegration

EP Monograph
Capsules should disintegrate within 15 min

NPcaps Shelf-Life
Shelf-life test methodology
Storage conditions 15 - 25C/35 - 65% RH in original closed carton
Visual aspect and transparency
Water content (LOD)
Mechanical performance (Tube-test)
Dissolution/disintegration behavior
Pre-lock, closing force
Filling test performance (GKF 400)

NPcaps: Stability of
Ascorbic Acid
Comparison of gelatin and NPcaps
filled with ascorbic acid and stored
for six weeks at 40C/75%RH

Gelatin shows brown discoloration


characteristic of Maillard reaction between
ascorbic acid and protein (amino groups)

Gelatin

No indication of discoloring for NPcaps

NPcaps

NPcaps Stability
Customer Relevance?
Anticipate shelf life to be identical to gelatin.
Avoid oxidation
Use less anti-oxydant

Compatibility with Colorants


Gelatin
Wide range of
achievable colors is
established
Capsule properties
(brittleness)
acceptable

Vcaps
Limited range
Iron oxides
Riboflavin

NPcaps
Under investigation

HGC vs Vcaps vs NPcaps: What are the Differences?


Gelatin
Capsules

Hypromellose
Vcaps

Pullulan
Npcaps

Functional Characteristics
Moisture Content
Dimensions

14%

6%

12%

WW Specification

WW Specification

WW Specification

Sizes
Cross Link
Susceptible to Maillard Reaction
Gelling Agent
Gelling Promoter
Machineability
In Vitro Disintegration*
In Vivo Disintegration*
Oxygen Barrier Properties*

All

00 - 4

00 - 5

Yes

No

No

Yes

No

No

Self Gelling

Gellum Gum

Carageenan

None

Potassium Acetate

Potasium Chloride

Excellent

Good

Excellent

2.18

2.54

1.46

28

Excellent

Poor

Best

Extensive

Limited

Will be Extensive

Glass-Like

Natural Looking

Glass-Like

No?

Yes

Yes

Limited Locations

Yes

Yes

Limited Locations

Yes

Yes

No

Yes

No

No

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

No

Limited

Yes

Difficult

Yes

No Experience

No

Yes

Yes

Approx. 5 sec

Approx. 12 sec

Approx. 4 sec

Extensive

Extensive

Extensive

Appearance
Colour Pallet
Appearance
Certifications
Non-GMO
Halal
Kosher-KO
Kosher-OU
Non-Animal
GRAS Status
Gluten Free
Starch Free
Preservative Free
Non- Animal Approval Japan
General
Manufacturing Locations
Enteric Coat
Cold Water Soluble
Oesophageal Transit Time
Excipient Compatability