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REVIEW ARTICLE Afzal Unnisa Sahana et.al / IJIPSR / 2 (9), 2014, 1988-2013
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com September Issue 1988
A REVIEW ON VEGGIE CAPS
1 Shahana Afzal Unnisa
*,
2Arunajyothi.G,
3 Harika.K,
4Nikhila.D,
5M.Srujan Reddy
1,2,3,4B.Pharm scholars, Samskruti College of pharmacy, Hyderabad, INDIA
5Department of Pharmaceutics, Samskruti College of Pharmacy, INDIA
Corresponding Author:
Shahana Afzal Unnisa
Department of Pharmaceutics,
Samskruti College of pharmacy,
Ghatkesar, Hyderabad, INDIA
Email: [email protected]
Mobile: +91 9573658485
International Journal of Innovative
Pharmaceutical Sciences and Research www.ijipsr.com
Abstract
Most of our empty gelatin capsules are made from animal products, which mean they aren’t a great
option for those who choose to live a vegetarian lifestyle. If you want to offer medications to this
specific audience, Capsule Depot offers vegetarian capsules to meet the needs of these patients. Today’s
health conscious consumers are focused on what they ingest more than ever before, and Capsugel has
products to help you meet this growing demand for vegetarian products with capsules that satisfy an
array of consumer cultural, lifestyle and dietary needs. Another major concern pharmaceutical
companies have is patients who are vegetarians. Hypromellose is the official Pharmacopeia name for
hydroxypropyl methylcellulose (HPMC). It is a cellulose derivative made from plants and is used to
make capsules without using materials of animal origin. Unlike gelatin capsules, vegetarian capsules will
not cause allergies to people who have sensitive skin. Hypersensitivity to cow and bovine products
triggers itchiness and hives when gelatin capsules are taken. There will be no such problems when
veggie capsules are taken.
Key words: Vegetarian, capsule, gelatin, dietary needs, HPMC.
REVIEW ARTICLE Afzal Unnisa Sahana et.al / IJIPSR / 2 (9), 2014, 1988-2013
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com September Issue 1989
INTRODUCTION
Definition: A solid dosage form in which the drug is enclosed in a hard or soft soluble container,
usually of a form of gelatin [1]. Or a small soluble container, usually made of gelatin that encloses
a dose of an oral medicine or a vitamin [2]. Or capsule- a pill in the fom of a small rounded
gelatinous container with medicine inside [3]. Or Capsules are solid dosage forms in which the
medication contained within gelatin shells. The medication may be powder, a liquid or a
semisolid mass. Capsules are usually intended to be administered orally by swallowing them
whole. Occasionally, capsules may be administered rectally or vaginally [4].
Fig. 1: images of capsules Fig. 2: Images of capsules
Fig. 3: Different parts of capsule
Mothes and Dublanc, two Frenchmen, are generally credited with the invention of the gelatin
capsules. Their patents granted in MARCH and DECEMBER of 1834, covered a method for
producing single- piece, olive-shaped, gelatin capsules, which were closed after filling a drop of
concentrated warm gelatin solution. The two piece telescoping capsule, invented by JAMES
NURDOCK of London (1848), was patented in England in 1865 [5].
REVIEW ARTICLE Afzal Unnisa Sahana et.al / IJIPSR / 2 (9), 2014, 1988-2013
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com September Issue 1990
In addition, to having advantages of elegance, ease of use and portability, capsules have become a
popular dosage form because they provide a smooth ,slippery, easily swallowed and tasteless shell
for drugs; the last advantage is particularly beneficial for drugs having an unpleasant taste or
odour. They are economically produced in large quantities and in a wide range of colours and
they generally provide ready availability of the contained drug since minimal excipient and little
pressure are required to compact the material, as is necessary in tableting [5].
Capsules are not usually used for the administration of extremely soluble materials such as
potassium chloride, potassium bromide, or ammonium chloride since the sudden release of such
compounds in the stomach could result in irritating concentrations. Capsules should not be used
for highly efflorescent or deliquescent materials. Efflorescent materials cause the capsule to
soften, where as deliquescent powders may dry the capsule shell to excessive brittleness. In some
cases, this dehydration may be retarded or prevented by the use of small amounts of inert oils in
the powder mixture [5].
History of Capsules [6]:
Revising the history through the changes in the forms of medicine
REVIEW ARTICLE Afzal Unnisa Sahana et.al / IJIPSR / 2 (9), 2014, 1988-2013
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com September Issue 1991
MATERIALS REQUIRED:
Beef extract
Gelatin
Calf skin
Pork,
Cattle and horse bones,
Split cattle hides
Collagen
Cellulose
Hypromellose, pullalan
1. Gelatin:
Gelatin or gelatin (from Latin: gelatus meaning "stiff", "frozen") is a translucent, colorless,
brittle (when dry), flavorless foodstuff, derived from collagen obtained from various animal by-
products. It is commonly used as gelling in food, pharmaceuticals, photography, and cosmetic
manufacturing. Substances containing gelatin or functioning in a similar way are
called gelatinous. Gelatin is an irreversibly hydrolyzed form of collagen. It is found in
most gummy candy as well as other products such as marshmallows ,gelatin dessert, and some ice
cream, dip and yogurt. Household gelatin comes in the form of sheets, granules, or powder.
Instant types can be added to the food as they are; others need to be soaked in water beforehand
[7].
Fig. 4: Gelatin powder Fig. 5: Gelatin substance
Fig. 5: Gelatin marketed formulation Fig. 6: Gelatin marketed formulation
REVIEW ARTICLE Afzal Unnisa Sahana et.al / IJIPSR / 2 (9), 2014, 1988-2013
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com September Issue 1992
Composition and properties:
Gelatin is a mixture of peptides and proteins produced by partial hydrolysis of collagen extracted
from the skin, bones, and connective tissues of animals such as domesticated cattle, chicken, pigs,
and fish. During hydrolysis, the natural molecular bonds between individual collagen strands are
broken down into a form that rearranges more easily. Its chemical composition is, in many
respects, closely similar to that of its parent collagen [8].
Photographic and pharmaceutical grades of gelatin are generally sourced from beef bones. Gelatin
forms a viscous solution when dissolved in hot water, which sets to a gel on cooling. Gelatin
added directly to cold water does not dissolve well. Gelatin is also soluble in most polar solvents.
Gelatin solutions show viscoelastic flow and streaming birefringence. The solubility of the gelatin
is determined by the method of manufacture. Typically, gelatin can be dispersed in a relatively
concentrated acid. Such dispersions are stable for 10–15 days with little or no chemical changes
and are suitable for coating purposes or for extrusion into a precipitating bath.
The mechanical properties of gelatin gels are very sensitive to temperature variations, the
previous thermal history of the gel, and time. These gels exist over only a small temperature
range, the upper limit being the melting point of the gel, which depends on gelatin grade and
concentration (but is typically less than 35 °C) and the lower limit the freezing point at which ice
crystallizes. The upper melting point is below human body temperature, a factor which is
important for mouth feel of foods produced with gelatin [9].The viscosity of the gelatin/water
mixture is greatest when the gelatin concentration is high and the mixture is kept cool (≈ 4 °C).
The gel strength is quantified using the Bloom test .
Structure of gelatin
REVIEW ARTICLE Afzal Unnisa Sahana et.al / IJIPSR / 2 (9), 2014, 1988-2013
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com September Issue 1993
Sources of gelatin:
Fig. 7: Beef bones Fig. 8: Different sources
Figure 9: Pork
Production [10, 11]
Gelatin is derived from pork skins, pork, horses, and cattle bones, or split cattle hides. The raw
materials are prepared by different curing, acid, and alkali processes which are employed to
extract the dried collagen hydrolysate. These processes may take up to several weeks, and
differences in such processes have great effects on the properties of the final gelatin products.
The manufacturing processes of gelatin consist of three main stages:
1. Pretreatments to make the raw materials ready for the main extraction step and to remove
impurities which may have negative effects on physico chemical properties of the final gelatin
product,
2.The main extraction step, which is usually done with hot water or dilute acid solutions as a
multi-stage extraction to hydrolyze collagen into gelatin, and finally,
3.The refining and recovering treatments including filtration, clarification, evaporation,
sterilization, drying, rutting, grinding, and sifting to remove the water from the gelatin solution, to
REVIEW ARTICLE Afzal Unnisa Sahana et.al / IJIPSR / 2 (9), 2014, 1988-2013
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com September Issue 1994
blend the gelatin extracted, and to remove the water from the gelatin solution, to blend the gelatin
extracted, and to obtain dried, blended and ground final product.
1. Pretreatment
Once the raw materials have been thoroughly cleaned, different process steps are carried out to
obtain gelatine depending on the type of raw material. There are two basic types of process:
Acid process - for gelatine type A:
The raw material (mostly pigskin) is subjected to a 24-h conditioning process. This involves
treatment with acid. After this, the gelatine can be extracted.
Alkaline process - for gelatine type B:
Here, the raw material (either ossein or bovine hide) is subjected to several weeks of treatment
with alkali. This enables the collagen structure to be gently transformed. The collagen it contains,
now softened by the pretreatment, can now be extracted using warm water.
2. Extraction
The pretreated raw materials are then treated with warm water in an extraction process, the
gelatine being removed in a number of process steps. The first gelatine extracts, obtained at
relatively low temperatures, are rather firm and have a light color. The extraction solutions
contain approximately 6 % gelatine. After these first extracts, the remaining material is treated
with fresh water but at a higher temperature. This sequence is continued until all the gelatine has
been extracted into solution.
A variation of this classical extraction process is the so-called continuous process. Here, warm
water and raw material are continuously fed into the extraction vessel and the gelatine solution is
continuously removed. The desired properties of the gelatine can be adjusted by means of
temperature and PH.
3. Purification
In this step, the gelatine solution obtained from the extraction process is placed in high-
performance separators where it is freed from residual traces of fat from the raw material and
from any insoluble particles. Precoat filters are then employed to remove fine-particle
contamination with the help of Kieselgur (diatomaceous earth), followed by filtration through
cellulose plates (as used in the beverage industry). Purification of the gelatine is completed by
removing any salts present using an ion exchange process.
REVIEW ARTICLE Afzal Unnisa Sahana et.al / IJIPSR / 2 (9), 2014, 1988-2013
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com September Issue 1995
4. Concentration
In the concentration step, multi-stage vacuum evaporators are used to remove part of the water
from the dilute gelatine extraction solution in a gentle process. In this way, the gelatine becomes
viscous and honey-like in consistency. This highly viscous solution is then passed through
polishing filters made of cellulose plates; these remove the very finest of particles that may
remain.
5. Drying
Subsequent to the concentration step, the gelatine solution is heat-sterilized for safety purposes; it
is then cooled and allowed to set. The gelatine is now in the form of "gelatine noodles"; these are
then run onto a conveyor belt of a dryer. Here, the gelatine is dried with sterile, pre-washed. Pre-
dried and filtered air. At the end of the drier, the now hard and brittle gelatine is broken up, milled
and stored in the warehouse until required for further use. Individual batches are only released for
further use on the successful completion of physical, chemical and bacteriological testing in the
lab.
6. Milling, sieving, blending
Milling, sieving and blending are the final three processing steps. Here, the dried gelatine is
customized to the requirements of individual customers. Once filled into silos, Big-Bags, sacks or
bags and after final release from the lab, the products are transported to the customers.
Figure 10: Schematic Representation of Manufacture of Gelatin
Capsule Manufacturing Process [12]:
1. Once raw materials have been received and released by Quality Control, the gelatin and hot
demineralized water are mixed under vacuum in R&J Engineering's Stainless Steel Gelatin
Melting System.
REVIEW ARTICLE Afzal Unnisa Sahana et.al / IJIPSR / 2 (9), 2014, 1988-2013
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com September Issue 1996
Fig. 11: Stainless steel gelatin melting system
2. After aging in stainless steel receiving tanks, the gelatin solution is transferred to stainless steel
feed tanks
Fig. 12: Feed tank receiving gelatin
3. Dyes, opacifants, and any needed water are added to the gelatin in the feed tanks to complete
the gelatin preparation procedure. The feed tanks are then used to gravity-feed gelatin into the
R&J Capsule Machine
Fig. 13: Addition of dyes, opacifants and others
4. Precision controls constantly monitor humidity, temperature, and gelatin viscosity
throughout the production process
Fig. 14: Precision control
REVIEW ARTICLE Afzal Unnisa Sahana et.al / IJIPSR / 2 (9), 2014, 1988-2013
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com September Issue 1997
5. 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.
Fig. 15: Entry of pin bars
6. In the Automatic section, capsule halves are individually stripped from the Pins.
Fig. 16: Stripping of capsules from pins
7. The cap and body lengths are precisely trimmed to a ±0.15 mm tolerance.
Fig. 17: trimming of capsule cap and body
8. The capsule bodies and caps are joined automatically in the joined blocks
Fig. 18: Joining of cap and body of capsule
REVIEW ARTICLE Afzal Unnisa Sahana et.al / IJIPSR / 2 (9), 2014, 1988-2013
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com September Issue 1998
9. Finished capsules are pushed onto a conveyer belt which carries them out to a container.
Fig. 19: Finished Capsules
10. Capsule quality is monitored throughout the production process including size, moisture
content single wall thickness, and colour.
Fig.20: Quality checking of capsules
11. Capsules are sorted and visually inspected on specially designed R&J Inspection Stations
Fig. 21: Visual inspection of capsules
12. Perfect capsules are imprinted with the client logo on high-speed capsule printing machines.
Capsules are now ready to be sterilized and packaged.
Fig. 22: Imprinting of capsules with logo
REVIEW ARTICLE Afzal Unnisa Sahana et.al / IJIPSR / 2 (9), 2014, 1988-2013
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com September Issue 1999
Uses: [13, 14, 15, 16]
Probably best known as a gelling agent in cooking, different types and grades of gelatin are used
in a wide range of food and non-food products: Common examples of foods that contain gelatin
are gelatin desserts, trifles, aspic, marshmallows, candy corn, and confections such
as Peeps, gummy bears, fruit snacks, and jelly babies. Gelatin may be used as a stabilizer,
thickener, or texturizer in foods such as yogurt, cream cheese, and margarine; it is used, as well,
in fat-reduced foods to simulate the mouthfeel of fat and to create volume without adding
calories.
Technical uses:
Capsules made of gelatin.
Certain professional and theatrical lighting equipment use colour gels to change
the beam colour. These were historically made with gelatin, hence the term colour gel.
Gelatin typically constitutes the shells of pharmaceutical capsules in order to make them
easier to swallow. Hypromellose is a vegetarian-acceptable alternative to gelatin, but is
more expensive to produce.
Animal glues such as hide glue are essentially unrefined gelatin.
It is used to hold silver halide crystals in an emulsion in virtually all
photographic and photographic papers. Despite some efforts, no suitable substitutes with
the stability and low cost of gelatin have been found.
Used as a carrier, coating or separating agent for other substances; for example, it
makes beta-carotene water-soluble thus imparting a yellow colour to any soft
drinks containing beta-carotene.
Gelatin is closely related to bone glue and is used as a binder in match heads
and sandpaper.
Cosmetics may contain a non-gelling variant of gelatin under the name hydrolyzed
collagen.
Gelatin was first used as an external surface sizing for paper in 1337 and continued as a
dominant sizing agent of all European papers through the mid-19th century. In modern
times it occasionally found in some glossy printing papers, artistic papers, playing cards,
and it maintains the wrinkles in crêpe paper.
REVIEW ARTICLE Afzal Unnisa Sahana et.al / IJIPSR / 2 (9), 2014, 1988-2013
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com September Issue 2000
Other uses
Blocks of ballistic gelatin simulate muscle tissue as a standardized medium for
testing firearms ammunition.
Gelatin is used by synchronized swimmers to hold their hair in place during their routines
as it will not dissolve in the cold water of the pool. It is frequently referred to as
"knoxing," a reference to Knox brand gelatin.
When added to boiling water and cooled, unflavored gelatin can make a home-made hair
styling gel that is cheaper than many commercial hair styling products, but by comparison
has a shorter shelf life (about a week) when stored in this form (usually in a refrigerator).
After being applied to scalp hair, it can be removed with rinsing and some shampoo.
It is commonly used as a biological substrate to culture adherent cells.
Also used by those who are sensitive to tannins (which can irritate the stomach) in teas,
soups or brews.
It may be used as a medium with which to consume LSD. LSD in gelatin form is known
as "windowpane" or "geltabs."
Gelatin is used to make the shells of paintballs, similar to the way pharmaceutical capsules
are produced.
Gelatin is also used as an ingredient in implantable medical devices, such as in some bone
void fillers.
Gelatin is also used in nail polish remover and makeup applications. The gelatin is often
tinted in different colours to match a model's natural skin tone.
Leaf or sheet gelatin is also used directly in food-based model-making, for example to
make translucent, edible, diamond-paned windows in gingerbread houses.
Gelatin can be used as a binding agent in India ink.
Gelatin may additionally be used as a technique within the process of fine art printmaking. The
prints are made by creating a block of gelatin and applying printing inks. The gelatin is made
using twice the normal amount of gelatin granules to the usual amount of water. Once set -
printmaking ink (usually water based) is applied to its surface. Other water based media may also
be applied. Items such as dried grass, leaves and paper stencils are placed onto the inked surface.
Gelatin monotype is best done with the use of medium to lightweight paper. This is gently pressed
onto the inked plate once the 'design' has been composed.
REVIEW ARTICLE Afzal Unnisa Sahana et.al / IJIPSR / 2 (9), 2014, 1988-2013
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com September Issue 2001
Disadvantages:
1. Water soluble material is difficult to incorporate.
2. Highly moisture sensitive. Gelatin is extremely water soluble, which helps it dissolve in the
body. The downside is that soft gelatin capsules are very sensitive to heat and humidity. In hot or
humid climates, soft gel caps may stick together or even break open before you have a chance to
use them. Keeping your soft capsules in the bathroom may also decrease their life expectancy,
since showers create a hot, humid climate that may not dissipate quickly.
3. Efflorescent material cannot be incorporated, they may cause softening/leaching
4. Deliquescent materials cannot be incorporated. They may cause hardening or brittle capsule.
5. More Costly. Many pharmaceutical companies do not have the equipment necessary to fill soft
gelatin capsules and have to transport the drugs to have them processed, adding to the cost. This
cost can increase the price the consumer pays. Certain health supplements, such as cod liver oil,
come in liquid and soft gel cap form. In most cases, the price is greater for the soft capsules than
for the liquid.
Advantages of gelatin capsules:
1. Soft gels are easy to swallow, once swallowed, release their contents very quickly. Have the
ability to mask odors and unpleasant tastes
2. Have an elegant appearance
3. Readily dissolve in the gastric juices of the digestive tract
4. They may enhance the bioavailability of the active ingredient
5. In specialized dosage form, soft gel can be made into chewable, extended release, captabs, etc.
It can also be used for ophthalmic preparations, e.g. aplicaps, vaginal/rectal suppositories.
6. Dosage Accuracy. Uniformity and precision dosage
7. Product Security. Dosage and formulation are tamper-resistant (a punctured or tampered soft
gels will leak or become discolored). Protection against counterfeit.
8. Product Stability. Sealed container, Protection from light for photosensitive formulations,
Protects drug from oxidation and degradation [17]
Sources of veggie caps:
Hypromellose, cellulose, pullalan.
REVIEW ARTICLE Afzal Unnisa Sahana et.al / IJIPSR / 2 (9), 2014, 1988-2013
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com September Issue 2002
Pullulan:
Pullulan is a polysaccharide polymer consisting of maltotriose units, also known as α-1,4- ;α-1,6-
glucan'. Three glucose units in maltotriose are connected by a α-1, 4 glycosidic bond, whereas
consecutive maltotriose units are connected to each other by a α-1, 6 glycosidic bond. Pullulan is
produced from starch by the fungus Aureobasidium pullulans. Pullulan is mainly used by the cell
to resist against dessication and predations, the presence of this polysaccharide also facilitate
diffusion of molecules both into and out of the cell. The presence of pullulan in the
environnement next to the cell favorises the formation of biofilm.
As an edible, mostly tasteless polymer, the chief commercial use of pullulan is in the manufacture
of edible films that are used in various breath freshener or oral hygiene products such
as Listerine Cool Mint of Johnson and Johnson (USA) and Meltz Super Thin Mints of Avery Bio-
Tech Private Ltd. (India). As a food additive, it is known by the E numberE1204 [18].
Structure of pullulan
REVIEW ARTICLE Afzal Unnisa Sahana et.al / IJIPSR / 2 (9), 2014, 1988-2013
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com September Issue 2003
Pullulan is a water-soluble glucan gum produced aerobically by growing yeast like
fungus Aureobasidium pullulans. It is a regularly repeating copolymer with the chemical structure
{→ 6)-α-D-glucopyranosyl-(1 → 4)-α-D-glucopyranosyl-(1 → 4)-α-D-glucopyranosyl-(1 →}n.
Thus the polysaccharide is viewed as a succession of α-(1 → 6)-linked (1 → 4)-α-D-triglucosides
i.e. maltotriose (G3). Pullulan have a wide range of commercial and industrial applications in
many fields like food science, health care, pharmacy and even in lithography. Due to its strictly
linear structure, pullulan is also very valuable in basic research as well as a well-defined model
substance. This review attempts to critically appraise the current literature on fungal
exopolysaccharide (EPS) ‘pullulan’ considering its microbial sources, structural geometry,
upstream processing, downstream processing, peculiar characteristics and applications [19].
The Advantage of Pullulan Vegetable empty capsule [20]
1) Pullulan Empty Capsule
A Brilliant Appearance:
Pullulan vegetable capsules are brilliantly clear and shiny. Finished products using Pullulan
vegetable capsules are visually attractive.
B Chemically Inert:
Pullulan is chemically inert, and does not react or cross link with contents the capsules are
intended to deliver.
C Excellent Oxygen Barrier:
Pullulan film is 300 times stronger oxygen barrier than HPMC film and 9 times stronger than
gelatin film of the same thickness. Pullulan capsules are the best choice for oxygen sensitive
materials.
D Environment Friendly and Health Conscious
Pullulan is water extracted from fungi grown on starch substrate, much like the mushroom
growing on fertile ground. There are no toxic chemicals involved in growing, harvest and extract
pullulan. So it is very natural and environment friendly.
Disadvantages[21]:
Pullulan is more sensitive than other materials (e.g. gelatin or HPMC) to low moisture conditions.
This sensitivity causes increase in shell brittleness at low water content. Unsatisfactory brittleness
means higher manufacturing losses, a poorer quality and higher costs.
REVIEW ARTICLE Afzal Unnisa Sahana et.al / IJIPSR / 2 (9), 2014, 1988-2013
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com September Issue 2004
Hypromellose
Hypromellose is the official Pharmacopeia name for hydroxypropyl methylcellulose (HPMC). It
is a cellulose derivative made from plants and is used to make capsules without using materials of
animal origin. Hypromellose (INN), short for hydroxypropyl methylcellulose(HPMC), is
a semisynthetic, inert, viscoelastic polymer used as an ophthalmic lubricant, as well as
an excipient and controlled-delivery component in oral medicaments, found in a variety of
commercial products.
As a food additive, Hypromellose is an emulsifier, thickening and suspending agent, and an
alternative to animal gelatin [22].
Structure of Hypromellose
Figure 23: physical form of HPMC
Chemistry [23]
Hypromellose is a solid, and is a slightly off-white to beige powder in appearance and may be
formed into granules. The compound forms colloids when dissolved in water. This non-toxic
ingredient is combustible and can react vigorously with oxidizing agents.
Hypromellose in an aqueous solution, unlike methylcellulose, exhibits a thermal gelation
property. That is, when the solution heats up to a critical temperature, the solution congeals into a
non-flowable but semi-flexible mass [24].
Formula: C56H108O30
INCI Name: Hydroxypropyl Methylcellulose
REVIEW ARTICLE Afzal Unnisa Sahana et.al / IJIPSR / 2 (9), 2014, 1988-2013
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com September Issue 2005
Recommended Usage: 0.1 - 2%
Physical Form: Off-White, free-flowing, light-weight, granular powder
Nonionic
Solubility: Soluble in Water/Not soluble in Oils
Viscosity: 2% in solution (water) = 18,000-120,000 cps [25].
Method of Preparation [26, 27, 28, 29]
5 g HPMC was dissolved in 100 mL of distilled water with continuous stirring.
After complete dissolution, the solution was filtered using filter paper to remove
undissolved particles. 2% PVP solution was prepared.
Now 50 mL of 5% HPMC solution and 50 mL of 2% PVP solutions were mixed together
and stirred continuously using magnetic stirrer for 20 min to ensure uniform mixing of the
solutions in the blend matrix.
During stirring 0.2% of Sorbitol predissolved in distilled water was added to the blend
solution and stirred for 10 more minutes.
The stirred solution was allowed for a while and then it is poured onto the clean leveled
glass plate and allowed to dry for a week.
After complete drying, the films were peeled out of the glass plate and stored in
desiccators to avoid moisture.
The prepared films appear to be transparent, smooth, and flexible.
This indicates that the two polymers may possibly be fully miscible with Sorbitol creating a new
single polymer matrix.
Following the same procedure, other samples of different concentrations and different wt
(%) of plasticizers were prepared.
Uses
• Cement renders
• Gypsum products
• Pharmaceutical
• Paints & coatings
• Food
• Cosmetics
• Detergents & cleaners
REVIEW ARTICLE Afzal Unnisa Sahana et.al / IJIPSR / 2 (9), 2014, 1988-2013
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com September Issue 2006
Use in whole grain breads [30]
Agricultural Research Service scientists are investigating using the plant-derived HPMC as a
substitute for gluten in making all-oat and other grain breads. Gluten, which is present in wheat,
rye and barley is absent (or present only in trace quantities) in oat and other grains. Like gluten,
HPMC can trap air bubbles formed by the yeast in bread dough, causing the bread to rise.
Although it has not been widely studied, it is predicted that whole grain breads made with HPMC
will have cholesterol-lowering effects.
Use in construction materials [31]
HPMC is used primarily in construction materials like tile adhesives and renders where it is used
as a rheology modifier and water retention agent.
Ophthalmic applications [32, 33]
Hypromellose solutions were patented as a semisynthetic substitute for tear-film. Its molecular
structure is predicated upon a base celluloid compound that is highly water soluble. Post-
application, celluloid attributes of good water solubility reportedly aids in visual clarity. When
applied, a Hypromellose solution acts to swell and absorb water, thereby expanding the thickness
of the tear-film. Hypromellose augmentation therefore results in extended lubricant time presence
on the cornea, which theoretically results in decreased eye irritation, especially in dry climates,
home, or work environments.
Advantages:
The non-animal origin of HPMC capsules ensures full compatibility with Halal and Kosher
certifications and compared to gelatin the raw material offers many technological benefits.
Due to its low moisture content which ranges from 4 to 6%, the HPMC is a perfect choice
for moisture-sensitive drugs.
Even after storage under harsh condition the capsules won't retain elevated moisture
levels.
Unlike gelatin, HPMC doesn't tend to form cross-linked bonds which results in high
stability and well-defined dissolution profiles.
Disadvantages:
Processing of a thin HPMC film is not so simple as with gelatin, the actual manufacturing
time become slightly longer.
REVIEW ARTICLE Afzal Unnisa Sahana et.al / IJIPSR / 2 (9), 2014, 1988-2013
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com September Issue 2007
Each manufacturer posses of his own patented process of gelation which subsequently
affects the dissolution profiles.
Thus, Hypromellose capsules from different manufacturers are not interchangeable for
every purpose (unlike in gelatin).
Hypromellose with gellan:
Capsugel launched DRcaps, a vegetarian capsule with acid-resistant properties.
They are made of hypromellose as well as Vcaps, but they contain a gelling agent and
water in addition.
Thanks to its properties, the capsules provide adequate protection from the stomach
environment without the need for aditional coating.
This makes it a perfect solution for drugs unsuitable for coating as well for saving extra
costs.
Drcaps provide the same benefits as other capsules which mean the ability to mask
unpleasant tastes and odors.
The moisture content of DRcaps is low (4-6%) [34].
Preparation of Veggie Capsules
The manufacturing of HPMC based capsules requires some modification to the molding machine
or to the formulation of the shell materials. HPMC gelling from solution occurs when the
temperature is increased while it is converted to its original solution as the temperature is
decreased, unlike gelatin solution. It means that the pins immersed in the dip pan containing the
HPMC solution must be of higher temperature (70°C) in order for the film to be formed. The pins,
the temperature of the pins must be further maintained post-dip to facilitate gelation until the
films dry out in the kilns [35, 36, 37, and 38]. Because HPMC shell walls are much weaker than
gelatin made shells, removal of the capsule from the pins and subsequent handling and filling are
difficult. To overcome these problems, three approaches were adapted. These approaches were to
use a stripper jaw with overcome these problems, three approaches were adapted.
These approaches were to use a stripper jaw with depressions on the inner surface increase the
formed HPMC film thickness and the use of gelling agents. The following gelling agents were
experimented: tamarind seed polysaccharide, carrageenan, pectin, curdlan, gellan gum and
furcellaran. Shionogi Qualicaps Co. (Japan) was able to produce HPMC carr capsule using the
standard machinery for the hard gelatin capsule by using HPMC gelling system containing
REVIEW ARTICLE Afzal Unnisa Sahana et.al / IJIPSR / 2 (9), 2014, 1988-2013
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com September Issue 2008
carrageenan as a gelling aid (kappa- and iota- carrageenan are preferred) and potassium chloride
as gelation promoter.
The company has a Quali-V registered trademark. European patent EP0592130 claims that
HPMC with higher whiteness, lower equilibrium moisture content and better film properties and
compatibility with drugs could be produced by exposing the materials to ultraviolet light in the
wavelength range of at least 200 nm [39]. The claim indicates that at the wavelength 253.7 nm,
the preferred conditions for ultraviolet radiation are a spacing of about 10 cm for about 10 hours.
An invention of Warner-Lambert Company (now with Capsugel that later became part of Pfizer)
have documented the preparation of HPMC capsules with hydrocolloids such as gellan gum
(HPMCgell) and sequestering agents (such as ethylenediaminetetraacetic acid, sodium citrate,
citric acid and their combinations 5% of the capsule shell materials comprised of approximately
equal proportions of both the hydrocolloid and the sequestering agent. The claim shows that these
capsules would have films that are less brittle (unlike those produced with carrageenan), no poor
disintegration in vivo and the film transparency is retained [40].
Uses of Veggie Capsules [41]
1. As in gelatin capsules, vegetarian capsules are also used for encapsulating all sorts of
substances such as medicines and vitamin supplements.
2. As already mentioned, they are a healthier alternative to gelatin capsules.
3. That means the utilization of gelatin capsules are also the same with veggie capsules. The only
difference is the material they are made of.
Advantages of Vegetarian Capsules [42]
Since they are plant-based foods, vegetarian capsules have some decided advantages over gelatin
capsules. Here are some of them.
• Unlike gelatin capsules, vegetarian capsules will not cause allergies to people who have
sensitive skin. Hypersensitivity to cow and bovine products triggers itchiness and hives when
gelatin capsules are taken. There will be no such problems when veggie capsules are taken.
• Those who have kidney and liver problems can now take their supplements with veggie caps
without worrying about the side effects. Before, they can’t take their supplements because of the
protein contained in gelatin capsules. Their liver and kidneys have to work hard to excrete the
protein contained in the gelatin capsules.
REVIEW ARTICLE Afzal Unnisa Sahana et.al / IJIPSR / 2 (9), 2014, 1988-2013
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com September Issue 2009
• Vegetarian capsules are also friendly to people who are eating kosher foods. Since these
capsules do not contain any animal by-product, they are sure that what they are eating is really
“clean” food with no traces of non-kosher animals.
Table 1: Differences between veggie capsules and gelatin capsules
SL.NO VEGGIE CAPS GELATIN CAPS
1 100% vegetarian. Animal derived-from cows and pork skin.
2 Hpmc is used Gelatin is used.
3 GRAS listed in FDA GRAS listed in FDA.
4 KOSHER CERTIFIED. KOSHER CERTIFIED.
5
Suitable for cultural, religious and
Vegetarian dietary requirements.
Not suitable for veggetarianvegetarian
requirements.
6
Suitable over wide range of temperatures
And humidity. Not that much suitable
7 Perfect for hygroscopic materials. Not suitable.
8
Compatiable with capsule filling
Machine, all sizes available. Same compatability
9 Doesn’t support bacterial growth. It doesn’t show bacterial growth under good
storing conditions.
Dietary restrictions and gelatin substitutes [43]
1. The consumption of gelatin from particular animals may be forbidden by religious or cultural
rules.
2.For example, Jewish kosher and Islamic Halal customs require gelatin from sources other than
pigs, like cows and/or fish and from animals slaughtered ritually.
3. Romani people are cautious of gelatin products that may have been made from horses, as their
culture forbids the consumption of horses.
4. There are companies that specify the source of the gelatin used.
5. Vegans and many vegetarians choose not to eat foods containing gelatin made from animals.
6. Likewise, Hindu & Jain customs may require gelatin alternatives from sources other than
animals, as many Hindus are vegetarian
7. Hindus who are not vegetarians will often consume gelatin from all sources except cow, which
is considered sacred.
8. Other people simply consider gelatin unpalatable due to the ingredients used in its production.
REVIEW ARTICLE Afzal Unnisa Sahana et.al / IJIPSR / 2 (9), 2014, 1988-2013
Department of Pharmaceutics ISSN (online) 2347-2154
Available online: www.ijipsr.com September Issue 2010
Marketed Products
Fig. 24: Biotin marketed product Fig. 25: 7-Ketodehydroepiandrosterone marketed
Product
Drug: biotin Drug: 7-Ketodehydroepiandrosterone
Category: vitamin b product Category: Steroid
Uses: promotes healthy skin, hair, nails. Uses: Increasing activity of the thyroid gland,
Boosting the immune system.
CONCLUSION
Since Vegetarian Capsules are plant-based foods, vegetarian capsules have some decided
advantages over gelatin capsules. As in gelatin capsules, vegetarian capsules are also used for
encapsulating all sorts of substances such as medicines and vitamin supplements. As already
mentioned, they are a healthier alternative to gelatin capsules. That means the utilization of
gelatin capsules are also the same with veggie capsules. The only difference is the material they
are made of. The consumption of gelatin from particular animals may be forbidden by religious or
cultural rules. Those who have kidney and liver problems can now take their supplements with
veggie caps without worrying about the side effects. Before, they can’t take their supplements
because of the protein contained in gelatin capsules. Their liver and kidneys have to work hard to
excrete the protein contained in the gelatin capsules.Vegetarian capsules are also friendly to
people who are eating kosher foods. Since these capsules do not contain any animal by-product,
they are sure that what they are eating is really “clean” food with no traces of non-kosher animals.
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