International Journal of Innovative Pharmaceutical ... (1).pdf · International Journal of...

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.

mailto:[email protected]




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].




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




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

http://en.wikipedia.org/wiki/Latin_language

http://en.wikipedia.org/wiki/Collagen

http://en.wikipedia.org/wiki/Food

http://en.wikipedia.org/wiki/Pharmaceuticals

http://en.wikipedia.org/wiki/Photography

http://en.wikipedia.org/wiki/Cosmetic_manufacturing

http://en.wikipedia.org/wiki/Cosmetic_manufacturing

http://en.wikipedia.org/wiki/Hydrolysis

http://en.wikipedia.org/wiki/Gummy_candy

http://en.wikipedia.org/wiki/Marshmallow

http://en.wikipedia.org/wiki/Gelatin_dessert

http://en.wikipedia.org/wiki/Ice_cream

http://en.wikipedia.org/wiki/Ice_cream

http://en.wikipedia.org/wiki/Dip_(food)

http://en.wikipedia.org/wiki/Yogurt




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

http://en.wikipedia.org/wiki/Viscous

http://en.wikipedia.org/wiki/Gel

http://en.wikipedia.org/wiki/Solvent

http://en.wikipedia.org/wiki/Birefringence

http://en.wikipedia.org/wiki/Human_body_temperature

http://en.wikipedia.org/wiki/Mouthfeel

http://en.wikipedia.org/wiki/Bloom_(test)




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




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.




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.




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




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




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




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.

http://en.wikipedia.org/wiki/Gelling_agent

http://en.wikipedia.org/wiki/Cooking

http://en.wikipedia.org/wiki/Gelatin_dessert

http://en.wikipedia.org/wiki/Trifle

http://en.wikipedia.org/wiki/Candy_corn

http://en.wikipedia.org/wiki/Peeps

http://en.wikipedia.org/wiki/Gummy_bear

http://en.wikipedia.org/wiki/Fruit_snack

http://en.wikipedia.org/wiki/Jelly_baby

http://en.wikipedia.org/wiki/Food_additive#Categories

http://en.wikipedia.org/wiki/Yogurt

http://en.wikipedia.org/wiki/Cream_cheese

http://en.wikipedia.org/wiki/Margarine

http://en.wikipedia.org/wiki/Mouthfeel

http://en.wikipedia.org/wiki/Colour_gel

http://en.wikipedia.org/wiki/Light_beam

http://en.wikipedia.org/wiki/Capsule_(pharmacy)

http://en.wikipedia.org/wiki/Hypromellose

http://en.wikipedia.org/wiki/Animal_glue

http://en.wikipedia.org/wiki/Silver_halide

http://en.wikipedia.org/wiki/Emulsion

http://en.wikipedia.org/wiki/Photographic_paper

http://en.wikipedia.org/wiki/Beta-carotene

http://en.wikipedia.org/wiki/Soft_drink

http://en.wikipedia.org/wiki/Soft_drink

http://en.wikipedia.org/wiki/Match

http://en.wikipedia.org/wiki/Sandpaper

http://en.wikipedia.org/wiki/Cosmetics

http://en.wikipedia.org/wiki/Hydrolyzed_collagen_(hydrolysate)

http://en.wikipedia.org/wiki/Hydrolyzed_collagen_(hydrolysate)

http://en.wikipedia.org/wiki/Sizing

http://en.wikipedia.org/wiki/Cr%C3%AApe_paper




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.

http://en.wikipedia.org/wiki/Ballistic_gelatin

http://en.wikipedia.org/wiki/Firearm

http://en.wikipedia.org/wiki/Ammunition

http://en.wikipedia.org/wiki/Synchronized_swimming

http://en.wikipedia.org/wiki/Hair_gel

http://en.wikipedia.org/wiki/Hair_gel

http://en.wikipedia.org/wiki/LSD

http://en.wikipedia.org/wiki/Paintballs

http://en.wikipedia.org/wiki/Gingerbread_house

http://en.wikipedia.org/wiki/India_ink

http://en.wikipedia.org/wiki/Printmaking

http://en.wikipedia.org/wiki/Monotype




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.




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

http://en.wikipedia.org/wiki/Polysaccharide

http://en.wikipedia.org/wiki/Polymer

http://en.wikipedia.org/wiki/Maltotriose

http://en.wikipedia.org/wiki/Glucan

http://en.wikipedia.org/wiki/Glucose

http://en.wikipedia.org/wiki/Glycosidic_bond

http://en.wikipedia.org/wiki/Glycosidic_bond

http://en.wikipedia.org/wiki/Starch

http://en.wikipedia.org/wiki/Fungus

http://en.wikipedia.org/wiki/Aureobasidium_pullulans

http://en.wikipedia.org/wiki/Oral_hygiene

http://en.wikipedia.org/wiki/Listerine

http://en.wikipedia.org/wiki/Food_additive

http://en.wikipedia.org/wiki/E_number




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.




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

http://en.wikipedia.org/wiki/International_Nonproprietary_Name

http://en.wikipedia.org/wiki/Semisynthesis

http://en.wikipedia.org/wiki/Polymer

http://en.wikipedia.org/wiki/Excipient

http://en.wikipedia.org/wiki/Colloid

http://en.wikipedia.org/wiki/Oxidising_agent

http://en.wikipedia.org/wiki/Methylcellulose

http://en.wikipedia.org/wiki/Congeal

http://en.wikipedia.org/wiki/Congeal

http://en.wikipedia.org/wiki/Critical_point_(thermodynamics)

https://www.google.co.in/search?sa=X&biw=994&bih=636&q=hypromellose+formula&stick=H4sIAAAAAAAAAGOovnz8BQMDgxkHnxCnfq6-QZpxvIGFlnp2spV-ckZqbmZxSVElhJWcmBOfnJ9bkF-al2KVll-UW5qT-F1w9oZExzDeVVnHr1QLK4pxT7s_DQB-MdldUwAAAA&ei=2a8eVJC4HoKNuATn0YKIDg&ved=0CKcBEOgTKAEwDQ




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




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.

http://en.wikipedia.org/wiki/Agricultural_Research_Service

http://en.wikipedia.org/wiki/Gluten




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




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.




• 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.




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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