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Chapter 3

Capsules

PRESENTED BY:

HARI KESH MEENALECTURER OF PHARMACEUTICS

G.D.MEMORIAL COLLEGE OF PHARMACY,JODHPUR
http://en.wikipedia.org/wiki/File:Prozac_pills.jpg

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Introduction - The definition of

capsules

Capsula Latin word: small box (fixedvolume!)

From a pharmaceutical stand point:

Capsules are solid dosage forms in whichmedicinal agents and/or inert substances areenclosed within a small shell of gelatin.

Gelatin capsule shells may be hard or softdepending on their composition.

Administration route of capsules

orally (whole or mixed with food or drink afteropening capsules)

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Introduction - The definition of

capsules

Capsules are solid dosage forms in which the drugsubstance is enclosed in either a hard or soft soluble

container or shell of a suitable form of gelatin.

Steps in capsule production1. Mixing of ingredient

2. Granulation and lubrication

3. Making of capsules4. Filling of capsules

5. Uniformity testing

6. Packing and labeling 3

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Introduction Advantages ofcapsules for oral administration

1. conveniently carried2. readily identified3. easily taken4. prescribing flexibility5. Efficiently and productively manufactured6. Packaged and shipped at lower cost and with

less breakage7. More stable and have a longer shelf-life

8. Empty hard gelatin capsules are often used inthe extemporaneous compounding ofprescriptions.

9. Tablets and capsules are sometimes used as the

source of a medicinal agent when it is nototherwise available.

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Introduction - Dosage forms thatmust be left intact

Dosage forms that must be left intact include:

enteric coated tablets: designed to pass through thestomach for drug release and absorption in intestine

extended/controlled release dosage forms: designed toprovide prolonged release of the medicament

sublingual or buccal tablets: formulated to dissolveunder the tongue or in the mouth

If a patient is unable to swallow an intact soliddosage form, an alternative product may beemployed, such as chewable tablet, instantdissolving tablet, oral liquid, suppository or

injection.

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Types of capsules

Gelatin capsule shells may be hard or softdepending on their composition.

Hard gelatin capsules

Soft gelatin capsules

Hardgelatin capsules: two-piece capsules

(body and cap).Softgelatin capsules: one-piece capsules.

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The application of hard gelatin capsules

used to manufacture most medicated agents

employed in clinical trials, to compare the

effect of an investigational drugs with those ofanother drug product or placebo

used in the extemporaneous compounding

The empty capsule shells consist of

gelatin, sugar, water, colorants (various dyes),and opaquants (titanium dioxide).

They can be clear, colorless and essentially

tasteless or they may be coloured with dyes

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Gelatin: Nature

Gelatin is a mixture of water solubleproteins (Mw ranges from 20-250 kDa).

Prepared by the hydrolysis of collagen(protein of the connective tissues),

followed by purification, concentration anddrying.

Main sources of collagen: Animal bonesand skin.

It is available in the form of a fine powder,a coarse powder, shreds, flakes or sheets.

Average molecular weight of gelatin varies

between 20,000 and 2,00,000. 8

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Types of gelatin

According to the hydrolysis processing:

Two popular grade of gelatin:

Pharmagel A and Pharmagel BType A: produced by acid hydrolysis, IEP

4.7 and pH 4.8 to 5.2

Type B: produced by basic (alkaline)hydrolysis, IEP 9.0 and pH 6.5 to 9.5

A mixture of the two types or only one can beused according to the required properties.

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Gelatin: Important propertiesThe main quality control item of gelatin

Bloom strength (a measure of gel rigidity) Viscosity degradation

Moisture content

transparency ash value

pH value

Iron: Its concentration depends on theiron content of the water used in itsmanufacture. 15ppm for gelatin used in

soft gelatin capsules. 10

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Gelatin as a capsule shell:WHY?

Non toxic

FDA approved in food stuff!!!

(risk of disease transmission).

Soluble in biological fluids atbody temperature.

Good film-producing material.

Displays thixotropic properties.

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Capsule shell:

Gelatin Opecifier

Water PreservativeColourants Wetting agents

Materials to be filled (formulation):

Active ingredients Diluents (filler)Glidants lubricants

Wetting agents Disintegrants

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Capsules shell:Water contentNormally, hard gelatin capsules contain between

13 to 16% of moisture. High % of water: softening and deformation,

microbial contamination.

Low % of water: brittle, breakdown upon use.

12-16 %: acts as a plasticizer.

Very critical during manufacturing and storage.

The solubility property of gelatin:

Insoluble in cold water, soften through the absorption ofup to ten times its weight of water;

soluble in hot water and in warm gastric fluid.

Gelatin, being a protein, is digested by proteolyticenzymes.

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Capsule shell: Colourants

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Mainly synthetic.

Water-soluble or water-insoluble.

Azo- or non-azo dyes.

Usually, a mixture is used.

Examples: erythrosine,indigocarmine.

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The manufacture of hardgelatin capsule shells

The shell consists of two parts, the capsule body and thecapsule cap.

The body is longer and slightly smaller in diameter thanthe cap.

Shape is mainly oblong.

The process of capsule shell production with the peg/pinmethod:

dipping drying stripping trimming joininga) The thickness of the gelatin walls must be strictly controlled.

b) The caps are slightly larger in diameter than the bodies.

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Manufacture of Hard Gelatin Capsules

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1. Shell composition :

Gelatin :

Prepared by the hydrolysis of collagen.

Gelatin in its chemical and physical properties,

depending upon the source of the collagen andextraction.

There are two basic types of gelatin:

Type A and Type B. The two types can be differentiated by their

isoelectric points (7.0 9.0 for type A and 4.8 5.0

for type B) and by their viscosity and film formingcharacteristics.

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Manufacture of Hard Gelatin Capsules

Combination of pork skin and bone gelatin are often

used to optimize shell characteristics.The physicochemical properties of gelatin of most

interest to shell manufactures are the bloom strength

and viscosity.Colorants :

Various soluble synthetic dyes (coal tar dyes) and

insoluble pigments are used.

Not only play a role in identifying the product, but

also may play a role in improving patient compliance.

E.g., white, analgesia; lavender, hallucinogenic effects;

orange or yellow, stimulants and antidepressants.

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Opaquing agents :

Titanium dioxide may be included to render the

shell opaque.

Opaque capsules may be employed to provide

protection against light or to conceal the contents.

Preservatives :

When preservatives are employed, parabens are

often selected.

Manufacture of Hard Gelatin

Capsules

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2) Shell manufacture :

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I. Dipping :

Pairs of the stainless steel pins are dipped into the dippingsolution to simultaneously form the caps and bodies.

The pins are at ambient temperature; whereas the

dipping solution is maintained at a temperature of about

50

0

C in a heated, jacketed dipping pan. The length of time to cast the film has been reported to be

about 12 sec.

II. Rotation :

After dipping, pins are elevated and rotated 2-1/2 timesuntil they are facing upward.

This rotation helps to distribute the gelatin over the pins

uniformly and to avoid the formation of a bead at the

capsule ends.

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III.Drying :

The racks of gelatin coated pins then pass intoa series of four drying oven.

Drying is mainly done by dehumidification.

A temperature elevation of only a less degreesis permissible to prevent film melting.

Under drying will leave the films too sticky for

subsequent operation.

IV. Stripping :

A series of bronze jaws strip the cap and body

portions of the capsules from the pins.

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V. Trimming :

The stripped cap and body portions aredelivered to collects in which they are firmly

held.

As the collects rotate, knives are broughtagainst the shells to trim them to the required

length.

VI. Joining :

The cap and body portions are aligned

concentrically in channels and the two portions

are slowly pushed together.

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Some improvements to hard gelatin capsule shells capsule-making pegs (body-making or cap-making pegs):

general rounded shape pegs tapered pegs

tapered rims, indentations and locking grooves:

straight-walled capsule shell tapered rim capsule shellwith indentations and locking grooves

a) The tapered rims avoid splitting;

b) The indentations prevent premature opening;

c) The grooves lock the two capsule parts together afterthe capsule has been filled.

extension capsule cap (CONI-SNAP SUPRO)

increase the security of the contents and the integrity ofthe ca sule

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Tamper-evident sealing and imprinting Tamper-evident sealing : through various capsule

sealing techniques

Imprintingwhich signals will be imprinted on finished capsules?

a) names and monograms of the manufacturer

b) the assigned national drug code (NDC) number

c) other markings making the product identifiable anddistinguishable from other products

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Capsule sizes

How to select capsule size?

1) the amount of fill material to be encapsulated

2) the density and compressibility of the fill

3) The final determination largely may be the result of trial. The sizes of empty capsulesThere are different sizes: from OOO (biggest) to 5 (smallest),

different filling capacity (60 mg to 1 g) depending on thedensity.

For human use: 000(the largest), 00, 0, 1, 2, 3, 4, 5 (the

smallest)

For veterinary use: Larger capsules are available.

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Capsule size and body fillvolumes

S.No. Capsule Size Body Volume(ml)

Body Weight(gm)

1. 000 1.30 1.00

2. 00 0.95 0.65

3. 0 0.68 0.50

4. 1 0.50 0.32

5. 2 0.37 0.25

6. 3 0.30 0.20

7. 4 0.21 0.15

8. 5 0.13 0.10

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For veterinary use larger capsules No., 10, 11 and 12 approx

capacities of 30, 15 and 7.5 gms. are also marketed.

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Preparation of filled hardgelatin capsules

The general steps of preparation

1) developing and preparing the formulation and

selecting the size of capsule.

2) filling the capsule shells.3) capsule sealing (optional).

4) cleansing and polishing the filled capsules.

The selection of capsule size For a commercial product: during the product

development stage

In the extemporaneous compounding of prescriptions

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Developing the formulation andselection of capsule size

The goal of developing a capsule formulation is to preparea capsule with

How to get to the goal?

1) pharmaceutical processing

2) pharmaceutical excipient

The pharmaceutical processing in the preparation of filledhard gelatin capsules

1) blending: uniform powder mix, uniform drugdistribution

2) comminution/milling: 50~100 microns, suitable for adrug of low dose (10mg or greater)

3) micronization: 10~20 microns, suitable for drugs oflower dose

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The pharmaceutical excipient in the preparationof filled hard gelatin capsules (continued)

3) Lubricant or Glidant: to enhance the flow propertiesof the powder mix

e.g. fumed silicon dioxide, magnesium stearate,calcium stearate, stearic acid, or talc

#: magnesium stearate, water-proofing characteristics,retard penetration of the GI fluids, delay drug

dissolution and absorption4) Wetting agents: to facilitate wetting of the dry powder

e.g. surfactants, as sodium lauryl sulfate

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The form of filling material in capsules:1) powder or granulate

2) pellet mixture

3) paste or wetted mass: the mixture of liquid and an inert

powder4) capsule

5) tablet

6) liquids: fixed or volatile oils (locking or sealed gelatin

capsules)

7) eutectic mixtures: mixed with a diluent or absorbent toseparate the interacting agents and to absorb anyliquefied material

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Examples of filled hard gelatin capsules

1) Tetracycline capsules

Active ingredient: Tetracycline hydrochloride, 250 mg

Filler: Lactose

Lubricant/Glidant: Magnesium stearate

Capsule colorants: omitted

Capsule opaquant: Titanium dioxide

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Filling hard capsule shells

2. The pouring methodsuitable for filling a small number of capsules in

the pharmacy

suitable for granular material

3. Hand-operated capsule filling machines

Hand operated and electrically operatedmachines are in practice for filling the capsules

but for small and quick dispensing handoperated machines are quite economical.

These machine are very simple to operate, canbe easily dismantled and reassembled.

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Filling of hard gelatin capsules

Equipment used in capsule filling operations

involves one often of two types of filling

systems.

Zanasi or Martelli encapsulator:

Forms slugs in a dosatar which is a hollow

tube with a plunger to eject capsule plug.

Hofliger-Karg machine:

Formation of compacts in a die plate using

tamping pins to form a compact.

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In this both system, the scale-up process

involve bulk density, powder flow,

compressibility, and lubricant distribution.

Overly lubricated granules are responsible for

delaying capsule disintegration and dissolution.

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OSAKA MODEL R-180

SEMI AUTOMATIC CAPSULE

FILLING MACHINE

Difficulties in filling the capsules

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Deliquescent and hygroscopic powders: agelatin capsule contains water which is extractedor taken up by a hygroscopic drug and renders thecapsule very brittle which leads to cracking of thecapsule.

The addition of absorbent like magnesiumcarbonate or light magnesium oxide overcomesthis difficulty provided the capsules are packed intightly closed glass capsule vials.

Eutectic mixtures: certain substances whenmixed together tend to liquefy or form a pastymass due to the formation of a mixture which has

a lower melting point than room temperature. 42



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The absorbents used are magnesium oxide andkaolin.

Another method in dealing with such typedifficulty is that the substances are mixedtogether so as to form a eutectic mixtures, then

absorbent like MgCO3 or Kaolin is used Addition of inert powders:when the quantity of

the drug to be filled in capsules is very small

and it is not possible to fill this much smallamount in capsules then inert substances or adiluents is added so as to increase the bulk ofthe powder which can be easily filled in

capsules.



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Filling of granular powders: some powderswhich lack adhesiveness and most granularpowders are difficult to fill in the capsule bypunch method because they are not

compressible and flow out of the capsule assoon as they are lifted from the pile of thepowder in to which they are punched.

To overcome this difficulty the non adhesivepowder should be moistened with alcoholand the granular powders should be reducedto powder before filling in to capsules.

44



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Use of two capsules: some of the manufactures

separate the incompatible ingredients of theformulation by placing one of the ingredients insmaller capsule and then placing this smallercapsule in a larger capsule containing the other

ingredients of the formulation.

Liquids:oil and liquids which will not dissolvegelatin may be filled into hard gelatin capsules.

When the quantity of the liquid to beincorporated is small, it is first mixed with aninert absorbent which is then added to anotheringredient, mixed thoroughly and filled in to

capsule. 45


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Capsule sealing

Sealing of the caps on to bodies is possibleby moistening the upper part of the bodyand slipping the cap on make the capsulestamper-evident

1) sealing with a colored band of gelatin2) heat welding

3) Thermally bonding at 40-45 with the helpof a melting-point-lowering liquid wettingagent

4) extemporaneously, by lightly coating theinner surface of the cap with a warm gelatin

solution

Cl i d li hi l

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Cleaning and polishing capsules

Small amount of powder may adhere to the

outside of capsules after filling.1) On a small scale, cleaning with a clean gauze

or cloth.

2) On a large scale, cleaning vacuumThe following steps are involved in thefinishing process:

1. salt polishing2. cloth dusting

3. brushing

4. inspection

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Differs from HGC in:

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1. Bloom strength: less than HGC

2. Amt of water and humidity.

3. Hydrophilicity.

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The pharmaceutical applications of soft gelatin

capsules are

1) as an oral dosage form for human or veterinaryuse

2) as a suppository dosage form for rectal use or forvaginal use

3) as a specialty package in tube form, for humanand veterinary single dose application oftopical,ophthalmic, and otic (ear) preparations, and rectalointments.

4) in the cosmetic industry, may be used for breath

fresher's, perfumes, bath oils & skin creams.

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The components of soft gelatin capsules1) gelatin2) glycerin or polyhydric alcohol3) water/moisture

4) preservative5) colorant6) markings

7) opaquants8) Flavors may be added and up to 5% sucrose maybe included for its sweetness and to produce achewable shell.

Manufacture of Soft Gelatin

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Manufacture of Soft Gelatin

Capsules

I. Composition of the shell: Similar to hard gelatin shells, the basic component

of soft gelatin shell is gelatin; however, the shell has

been plasticized. The ratio of dry plasticizer to dry gelatin determines

the hardness of the shell and can vary from 0.3-

1.0 for very hard shell to 1.0-1.8 for very soft shell.

Up to 5% sugar may be included to give achewable quality to the shell.

The residual shell moisture content of finished

capsules will be in the range of 6-10%.

S ft G l ti C l

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Soft Gelatin Capsules

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II. Formulation :

Formulation for soft gelatin capsules involves

liquid, rather than powder technology.

Materials are generally formulated to produce

the smallest possible capsule consistent with

maximum stability, therapeutic effectiveness andmanufacture efficiency.

The liquids are limited to those that do not have

an adverse effect on gelatin walls. The pH of the liquid can be between 2.5 and 7.5.

Emulsion can not be filled because water will be

released that will affect the shell.

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The types of vehicles used in soft gelatin capsules

fall in to two main groups:

1. Water immiscible, volatile or more likely more volatileliquids such as vegetable oils, mineral oils, medium-

chain triglycerides and acetylated glycerides.

2. Water miscible, nonvolatile liquids such as low

molecular weight PEG have come in to use morerecently because of their ability to mix with water

readily and accelerate dissolution of dissolved or

suspended drugs.

All liquids used for filling must flow by gravity ata temperature of 350c or less.

The sealing temperature of gelatin films is 37-

400

C.

P ti f ft l ti l

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Preparation of soft gelatin capsules

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III Manufacture process :

A. Plate process :The process involved

Placing the upper half of a plasticized gelatin sheet

over a die plate containing numerous die pockets, Application of vacuum to draw the sheet in to the

die pockets,

Filling the pockets with liquor or paste,

Folding the lower half of gelatin sheet back over

the filled pockets, and

Inserting the sandwich under a die press where

the capsules are formed and cut out.

Preparation of soft gelatin

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Preparation of soft gelatincapsules

The plate process(using a set of molds)The plates contain die pockets.

1) placing a warm sheet of gelatin on the bottom plate

2) pouring the liquid-containing medications

3) placing the second sheet of gelatin

4) putting the top plate of the mold into place

5) pressing the mold to form, fill, and seal the capsules

simultaneously6) removing and washing the capsule

Today, this equipment can no longer be purchased.

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The rotary die process (1933, R. P. Scherer)more efficient and productive

1) Liquid gelatin is formed into two ribbons2) The two ribbons are brought together3) Metered fill material is injected between the

ribbons

4) These pockets of fill-containing gelatin aresealed

Rotary die press

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y p

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Rotary die soft capsulemachine

The dies for production of softcapsule

C. Accogel process:

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g p

In general, this is another rotary process involving

A measuring roll,

A die roll, and

A sealing roll.

As the measuring roll and die rolls rotate, the

measured doses are transferred to the gelatin-linked pockets of the die roll.

The continued rotation of the filled die converges

with the rotating sealing roll where a second gelatin

sheet is applied to form the other half of the

capsule.

Pressure developed between the die roll and sealing

roll seals and cuts out the capsules.

Preparation of soft gelatin

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Preparation of soft gelatincapsules

The Accogelmachine (1949,

Cyanamid company)

This equipment is

unique in that it is

the only equipmentthat accurately fillspowdered dry solids.

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D B bbl h d

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D. Bubble method:

The Globex Mark II capsulator produces truly

seamless, one-piece soft gelatin capsules by abubblemethod.

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A concentric tube dispenser simultaneously

discharges the molten gelatin from the outer

annulus and the liquid content from the tube. By means of a pulsating pump mechanism, the

liquids are discharged from the concentric tube

orifice into a chilled-oil column as droplets thatconsists of a liquid medicament core within a

molten gelatin envelop.

The droplets assume a spherical shape under

surface tension forces and the gelatin congeals on

cooling.

The finished capsules must be degreased and

dried.


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E. The reciprocating die process

(1949, Norton company)

is similar to the rotary process in that ribbons ofgelatin are formed and used to encapsulate the

fill, but it differs in the actual encapsulatingprocess.

1) A set of vertical dies continually open and closeto form rows of pockets in the gelatin ribbons.

2) These pockets are filled with the medicationand are sealed, shaped, and cut out of the film.

3) The capsules fall into refrigerated tanks whichprevent the capsules from adhering to one

another.


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Three formulation strategies based on having a high

resting viscosity after filling have been described.

1. Thixotropic formulations,

2. Thermal-setting formulations,

3. Mixed thermal-Thixotropic systems.

The more lipophilic contents, the slower the release

rate.

Thus, by selecting excipients with varying HLB

balance, varying release rate may be achieved.

The nature of soft gelatin

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gcapsule shell

1) The gelatin is Pharmacopoeial grade with

additional specifications required by the capsulemanufacturer.

a) Bloom strength(measure of rigidity) :Load in

gms required to push a stand plunger 4mm intothe gel.

The gelatin used in HGC is of higher bloomstrength (200-250 gm) than that used forSGC(150gm)

b) viscosity:

Generally, 25 to 45 millipoise is acceptable.

c iron: 15 m

The nature of soft gelatin

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The nature of soft gelatincapsule shell

2) Plasticizersglycerin or Sorbitol or combinations of these

The ratio by weight of dry plasticizer to dry gelatindetermines the hardness of the gelatin shell.

0.4/1 hard

0.6/1 medium

0.8/1 soft

The ratio by weight of water to dry gelatin can vary from0.7-1.3 to 1.0.

3) The color of the gelatin shell

Formulation of soft gel

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Gelatine: Alkali processed(Type B) 40% of gelmass.

We can also use Type A acid gelatin.Plasticizer:20-30% of gel mass,its amount

depends on:1-Hardness 2- dissolution and Disintegrant.3- Stability. 4-Compatabile with all.5- appearance.Water:30-40% of gel mass, ensure proper

processing, excess water is removed by drying.In dry soft gels water 5-8% w/w, thus good

stability.Colourants and opacifier: asHGC

Formulation of soft gel

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The fill material of soft gelatin

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The fill material of soft gelatincapsules

1) liquids

a) water-immiscible volatile and nonvolatile liquids

b) water-miscible, nonvolatile liquids

c) water-miscible and relatively nonvolatile liquidse.g. propylene glycol, isopropyl alcohol

d) Liquids that can easily migrate through the capsuleshell cannot be encapsulated into soft gelatin capsules

2) solids (solutions, suspensions, pasty mass, drypowders, granules, pellets, or small tablets.)

Disadvantages of SGC

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Disadvantages of SGC

1. Special manufacturing equipment.2. Limited choice of excipients.

3. Any change in water % affect hardness.

4. Hygroscopic & volatile compounds cause

hardening.5. Acid & Alkalis cause hydrolysis & leakage.

6. Not for product Extract But,

Product Extract + carrier oil + beeswax + lecithin=encapsulation)

7. Fish oil has bad odour & taste, thus includesConc. Of flavor.

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The container and preservation

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The container and preservationcondition described in USP

containers1) light resistant container:

2) well-closed container:3) tight container:4) Hermetic seal Container :

Preservation conditions1)Freezer: -25 ~ -10; 2)Cold: 40 ;8)Protection from Freezing: (breakage of the container, loss

of strength or potency, destructive alteration of its

characteristics)

Compendial requirements for

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p qcapsules

Disintegration test for capsulesThe disintegration tests for hard and soft gelatin

capsules follows the same procedures and usesthe same apparatus as for uncoated tablets.

1) Method

The capsules are placed in the basket-rack assembly,which is repeatedly immersed 30 times per minute into athermostatically controlled fluid at 37 and observedover the time described in the individual monograph.

2) To fully satisfy the test, the capsules disintegratecompletely intoa soft mass having no palpably firmcore, and only some fragments of the gelatin shell.

Compendial requirements for

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p qcapsules

Dissolution test for capsules1) The apparatus, dissolution media and test is the

same as that for uncoated and plain coated tablets.

If the capsule shell interfere with the analysis, the

content of specified number of capsules can beremoved and the empty capsule shells dissolved inthe dissolution medium before proceeding with thesampling and chemical analysis.

2) Generally, when a dissolution test is applied to anexisting capsule product, the disintegration test isunnecessary.

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Compendial requirements forl

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capsules

Other requirements:

1) content labeling: the quantity of each activeingredient in each dosage unit.

2) stability testing

method: long-term stability testing, acceleratedstability test

aim: storage condition, shelf life

3) moisture permeation test: the USP requiresdetermination of the moisture permeationcharacteristics of single- unit and unit dose-containers to ensure their suitability for

acka in ca sules.

Inspecting, counting, packaging,

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spect g, cou t g, pac ag g,and storing capsules

1) Inspectingvisual or electronic inspection uniform in

appearance

2) Counting

a) counting tray;b) counting and filling machines

3) Packaging

unit dose and strip packaging (sanitary,

identifiable, safe)4) Storing

in tightly capped container in a cool, dry

place

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CAPSULE

POLISHING

MACHINE

AUTO MATICCAPSULE

ARRANGEMNT

The Gel Mass (Capsule shell)

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The gel is prepared in a300-litre stainless

steel vessel.

HOW?

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The Gel Mass (Capsule shell)Gelatine powder

mixed with water and glycerine that is then

heated and stirred under vacuum.

The molten gelatin mass is then decanted into 200-kg mobile vessels where colours and flavours canbe added using a turbine mixer that ensuresconsistency of the gelatin mass.

This mass is kept at a constant temperature until itis needed for the next stage of the process

The Medicine (Capsule fill)

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The medicine preparation area has a standard

range of mixers, homogenizers and millingequipment for the preparation of the fills. Theproduct being prepared dictates whatequipment has to be utilized.

For simple oils the material is decanted into a200 kg mobile vessel, positioned on a floorscale, blanketed with Nitrogen, if required, andthen sealed ready for the next stage of the

process. Blends of oils follow a similar process but a

Silverson mixer is used to ensure a uniform mixis achieved.

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Inspection

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To Summarize!

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References

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1. The theory and practice of industrial pharmacy.

Leon Lachman, Herbert A. Lieberman, Joseph L.

Kanig. Third edition. Varghese publishing house.

Page no. 681-703.

2. Pharmaceutical dosage forms: Tablets. Volume 3.

second edition. Leon Lachman, Herbert A.Lieberman, Joseph B. Schwartz. Page no. 303-365.

3. Pharmaceutical process scale up edited by

Michael Levin.4. Modern pharmaceutics. Edited by Gilbert S.

Banker & Christopher T. Rhodes. 4th edition.

5. www.google.com

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