Types of Capsules:
Depending upon the
form of the capsule shell the capsule may be classified into two types as:
-----
Hard gelatin capsule
Soft gelatin capsule
Hard gelatin
capsule:
Hard gelatin capsules
are usually made up of a base containing plasticizers and water. The base may
also contain preservatives, colors, flavors and sugars. Capsule shells are made
up of two cylindrical halves, one slightly large in diameter bur shorter n
length and the other slightly shorter in diameter and longer in length. The
former in shown as cap and latter as body of the capsule. The drug is filled in
the narrower and longer half over which the other half is fitted as a cap.
The hard gelatin
capsule is made in a range of eight sizes from size 000 (the largest) to size 5
(the smallest). The most popular sizes in practice are size 0 through to
4.
Size Volume
in ml
5 0.13
1 0.48
4 0.20
0 0.67
3 0.27
00 0.95
2 0.37
000 1.36
Soft gelatin
Capsule:
These capsules are
soft and elastic in nature which are prepared from gelatin and water to which
glycerin, sorbitol or propylene glycol has been added as a plasticizer which
make the capsules flexible. They usually contain a preservative to prevent the
growth of bacteria and fungi. These capsules are available in a number of
shapes and sizes, e.g. spherical, ovoid, cylindrical and tubes. The contents of
soft capsules may very from 0.1ml to 30ml.
Advantages:
A compression stage
is not included in the manufacturing process.
The dose content
uniformity is optimized because the drug is dissolved or dispersed in a liquid
which is then dosed volumetrically into the capsules accurately.
Drugs sensitive to
oxidation or hydrolysis on long term storage can be protected from the
environment by solution or dispersion in oil and encapsulation by gelatin.
The drug is dissolved
or dispersed in a water miscible or oily liquid and when the capsule is
ingested, the capsule breaks and the solution dissolves or is emulsified to
give a drug dispersion of high surface area and good bioavailability.
Uses: The soft
gelatin capsules are used for: --------.
Water-immiscible
volatile and nonvolatile liquids such as vegetable and aromatic oils, aromatic
and aliphatic hydrocarbons, chlorinated hydrocarbons, ethers, esters, alcohol
and organic acids.
Water-miscible,
nonvolatile liquids, such as polyethylene glycols, and nonionic surface active
agents as polysorbate 80.
Water-miscible and
relatively nonvolatile compounds, as propylene glycol and isopropyl alcohol,
depending on factors as concentration used and packaging conditions.
Filling liquids and
semisolids Vit. Preparations such as halibut liver oil, Vit. A & D and
multivitamins.
Containing eye, ear,
nose and throat preparations.
As a substitutes for
suppositories.
Packing cosmetics,
flavors and food concentrates.
Ophthalmic ointments
are frequently packed in unit dose capsules.
Difference between
soft and hard gelatin capsules:
Characteristics
Soft gelatin capsule
Hard gelatin capsule.
Shape
Spherical, Oval,
Cylindrical and tube
Usually cylindrical
Filled medicaments
May be solid, liquid
and semi solid
Only for solid
Boundary wall
Soft and flexible
Firm and rigid.
Moisture content in
gelatin
0.7 - 1.3 parts of
water to each part of dry gelatin
13% – 16%
The gelatin wall
Usually contain
plasticizers, water and preservative
Usually contain
plasticizers, water, preservatives, color, flavors and sugar.
Formulation process
One continuous
process, e.g. filling & formulation in same time.
Two step process,
first the shell formation and then the filling process is completed.
Volatile drug
substance
Suitable for filling
Non suitable for
filling
Capacity
May contain 0.1 –
30ml.
May contain 30 –
600mg.
Structure
Only the body
The body and the cap
Gelatin strength.
Low bloom gelatin
used
High bloom gelatin
used.
Dry Glycerin/ Dry
Gelatin
0.8/1
0.4/1
Example
Indomethacin BP
Tetracycline HCl BP
( - tocophrol acetate
100mg
vitamin A 2lac
Raw materials for
gelatin capsules
The materials used
along with active ingredients and additives to prepare capsule shell both for
hard and soft gelatin capsules are generally: --------
- Gelatin
- Plasticizers
- Colors
- Preservatives
The first step of the
process is to prepare a gelatin solution in demineralized water or a mixture of
demineralized water and glycerol. To this are added, colorants, preservatives
and process aids depending upon the type of capsules required.
Gelatin:
Gelatin is a
heterogeneous product derived by irreversible hydrolytic extraction of treated
animal collagen and as such, it never occurs naturally. Its physical and
chemical properties are mainly functions of the parent collagen, method of
extraction, pH value, thermal degradation and electrolyte content. Common
sources of collagen are animal bones, hide portions and frozen pork skin. Bone
and skin gelatins are readily available in commercial quantities in most areas
of the word. Gelatin is insoluble in cold water but soluble in hot water and in
warm gastric juice gelatin capsule rapidly dissolves and exposes its contents.
Gelatin being a protein is digested by proteolytic enzymes and absorbed.
The properties of the
gelatin which are most important for the capsule manufacturer are: ------
Bloom strength: Bloom
strength of gelatin is a measure of the cohesive strength of the cross linking
that occurs between gelatin molecules and is proportional to the molecular
weight of the gelatin. It is expressed as the load in grams required pushing a standard
plunger a set distance into a prepared gelatin gel (6.66% solution at 100C).
The gelatin used in hard capsule manufacture is termed high bloom gelatin
whereas for soft capsules lower bloom material is used.
Viscosity: Viscosity
of gelatin is a measure of the molecular chain length and determines the
manufacturing characteristics of the gelatin film. It is determined on a 62/3%
concentration of gelatin in water at 600C. The viscosity for gelatin can range
from 25 – 45 millipoise. It is used by the manufacturers of both types to
control the thickness of the films or sheets.
Iron contents: Iron
is always present in the raw gelatin and its concentration usually depends on
the iron content of the large quantities of water used in its manufacture. Gelatins
used in the manufacture of soft gelatin capsules should not contain more than
15 ppm of this element.
The advantageous
qualities of gelatin: Gelatin is the major component of capsules due to their
four essential basic properties described below: --------
It is non toxic.
It is widely used in
foodstuffs and is acceptable for use in every country in the word.
It is readily soluble
in biological fluids at body temperature.
It is a good film
forming material.
As a solution in
water or a water glycerol blend it undergoes a reversible phase change form a
sol to a gel at temperatures only a few degrees above ambient. This property
enables films of gelatin to be prepared easily.
Preparation of
gelatin formation:
Gelatin is a
substance of natural origin. It is prepared by the hydrolysis of collagen which
is the main protein constituents of connective tissues. Common sources of
collagen are animal bones, hide portions and frozen pork skin. Bone and skin
gelatins are readily available in commercial quantities in most areas of the
word.
Types: There are two
types of methods for gelatin formation: --
Type A: Gelatin is
derived from an acid treated precursor and exhibits an isoelectric point in the
region of pH 9.
Type B: Gelatin is
derived from an alkali treated precursor and exhibits an isoelectric point in
the region of pH 4.7.
The choice of
manufacturing methods depends upon the nature of the raw materials; skins are
mainly acid processed whereas bones are usually basic processed. Animal bones
need additional treatment, in that they first need to be decalcifies and to
produce ossein, a soft sponge like material.
Uses:
The gelatin is used
in capsule manufacturing for its bloom strength.
The viscosity of gelatin
also used to control the thickness of the films or sheets.
They are used in
reducing haze or cloudiness in the finished capsule.
Plasticizer:
Plasticizers are the
substances which are added to plastic formulation to achieve softness and
flexibility. DEHP is a commonly used plasticizer. Among the plasticizer
Glycerin USP, Sorbitol USP, Pharmaceutical Grade Sorbitol Special and
combination of these are the most prevalent. Further Propylene glycol, Sucrose
and Acacia etc. are also used in this purpose.
The ratio by weight
of dry plasticizer to dry gelatin determines the hardness of the gelatin shell.
The ratio by weight of water to dry gelatin can vary from 0.7 – 1.3 (H2O) to
1.0 (dry gelatin) depending on the viscosity of the gelatin being used.
Hardness
Ratio
Dry Glycerin/ Dry
Gelatin
Application
Hard
0.4/1
Oral, oil based or
shell softening products
Medium
0.6/1
Oral, tube, vaginal
oil based, water miscible based or shell hardening products.
Soft
0.8/1
Tube, vaginal, water
miscible based or shell hardening products.
0.35/1
Oral capsules with
oil fills where final capsule should be hard
0.46/1
Oral capsules with
oil fills where shell requires to be more elastic
0.55-0.65/1
Capsules containing
oils with added surfactant or products with bydrophilic liquid fills.
0.76/1
Oral capsules where a
chewable shell is required.
Uses:
It is used to achieve
softness and flexibility.
It is commonly used
in plastic materials such as vinyls, cellulosies etc.
It is also used with
stabilizers.
Coloring agents:
Coloring agents may
be defined as components employed in pharmacy solely for the purpose of
imparting color. They may be classified into two kinds, as: -------
Soluble dyes: The
soluble dyes are mainly synthetic origin. E.g. Nitroso-dyes, nitro-dyes,
azo-dyes, oxazines, thiazines, xanthenes, anthraquinones, acridines and
quinolines etc. They are used in: ----
Coloring fabrics
Various artistic
purposes
Mixture of dyes to
make capsules color.
Insoluble pigments:
The pigments used of two types:---
Titanium dioxide: It
is used in the largest quantity (0 – 0.5%). It is white and used as an
opacifying agent.
The iron oxides:
Three pigments are used: Black, Red and Yellow.
For the manufacture
of bi-colored soft gelatin capsules aluminium lakes are used to prevent color
transfer between two layers of the capsule.
Preservatives:
In the common
pharmaceutical sense a preservative is a substance that prevents or inhibits
microbial growth and may be added to pharmaceutical preparations for this
purpose to avoid consequent spoilage of the preparations by microorganisms.
Preservatives are
sometimes added to capsules as an in process aid in order to prevent
microbiological contamination during manufacture. When soft gelatin capsules
are stored in non protective packages, antifungal agents are added to them to
prevent growth on their surfaces. Example:
Potassium sorbitate and methyl, ethyl and propyl hydroxybenzoate.
Preparation of Filled
Hard Gelatin Capsule
The preparation of
hard gelatin capsules may be divided into the following steps: ---------
Developing and
preparing the formulation and selecting the size capsule.
Filling the capsule
shells.
Capsule sealing
(optional)
Cleaning and
polishing the filled capsules.
Capsule formulation
and selection of capsule size:
Hard gelatin capsules
are generally used to encapsulate between about 65mg and 1gm of powder
material, including drug and any diluent required. All formulations for filling
into capsules must possess two basic requirements which are: -------
Be able to be
accurately dosed into the capsule shell.
Release their active
contents in a form which is available to the patients.
If the dose of the
drug or the amount of drug to be placed in a single capsule is inadequate to
fill the volume of the capsule, a diluent is necessary to add the proper degree
of bulk to the drug to produce the proper fill. But when the amount of drug is
large enough to fill a capsule completely a diluent may not be required.
Lactose in a common diluent used in capsule filling.
Lubricants are used
to facilitate the flow of the powder when an automatic capsule filling machine
is utilized. Magnesium stearate, Calcium stearate or talk (about 0.25 – 1%)
generally used as lubricant in capsule making.
The practice of
adding surfactants in capsule formulation is to facilitate the wetting of the
drug substance by the bathing of gastrointestinal fluid and thus to promote
dissolution of the drug.
To determine the size
of capsule to be used or the fill weight for a formulation the following
relationship is used: --
5 to 10% excess of
each ingredient is calculated just to compensate for the loss of material due to
sticking to the pestle, the motor and any other surfaces that come into contact
during operation. When the amount of drug representing a usual dose is too
large to place in a single capsule, two or more capsules may be required to
provide the desired dose of that particular drug.
In all instances, the
amount of drug to be present in a single capsule is first determined and the
amount of diluent or inert materials if any is determined subsequently on the
basis of its being needed to add bulk to the formulation.
Filling the capsule
shells:
Capsule filling may
be operated hand or machine. In both process the single mechanism is involved
which is as follows: ------
First the weighed
amount of active ingredients and with out additives are prepared for the
filling operation. Now the capsule shells are taken to separate them into cap
and body. The body is then filled with the prepared powder mixture or granules.
Now the cap is pressed on the body to close it. A properly filled capsule
should have its body filled with the drug mixture and its cap fully extended
down the body so as to enclose the powder in the body. The cap is not used to
hold powder but to retain it. Finally the filled capsule shells are ejecting
for cleaning and polishing.
Capsule sealing:
The filled capsules
may be sealed by the following process: -------
A heat welding
process that fuses the capsule cap to the body through the double wall
thickness at their juncture.
Utilizing a melting
point lowering liquid wetting agent in the contact areas of the capsule’s cap
and body and then thermally bonds the two parts using low temperatures
(40-450C).
Extemporaneously
prepared capsules may be sealed by lightly coating the inner surface of the cap
with a warm gelatin solution immediately prior to placement on the filled
capsule body.
Cleaning and
Polishing capsules:
Small amounts of
powder may adhere to the outside of capsules after filling. The powder may be
bitter or otherwise unpalatable and should be remove before packaging or
dispensing.
On a small scale,
capsules may be cleaned individually or in small numbers by rubbing them with a
clean gauze or cloth. On the large scale, may capsule filling machines are
affixed with a cleaning vacuum that removes any extraneous material from the
capsules as they exits the equipment. (Accela-Cota apparatus – Eli Lilly and
company.)
NAME SOME CAPSULE
FILLING MACHINES
Machine name
Company name
Lilly ROTOFIL
Eli Lilly & Co., Indianapolis , IN.
Farmatic Model 2000/60
G.B. Gundi Bruno
S.p.A., Bologna , Italy
H & K Model 602
Robert Bosch GmbH, Waiblingen , West
Germany
Macofar Model MT-12
Macofar, Bolonga , Italy
mG2 Model G36
mG2 Macchine
Automatiche, Bolonga , Italy
Sharples-Stokes, Warminster , PA.
Perry Model CF
ACCOFIL
Perry Industries, Green Bay , WI
Zanasi Model LZ-64
Zanasi, S.p.A., Bolonga , Italy
Quality control of
capsule
Quality control is a
part of quality assurance. Quality control refers to the process of striving to
produce a perfect product by a series of measures requiring an organized effort
by the entire company to prevent or eliminate errors at every stage in production.
It concerns quality control of raw materials, finished products and packaging
materials.
Whether capsules are
produced on a small or large scale all of them are required to pass the quality
control tests such as disintegration test, weight variation test, contents
uniformity tests, certain visual tests etc. the hard and soft gelatin capsules
should be subjected to following tests for their standardization: ----
Shape and size
Color
Thickness of the
capsule shell
Disintegration test
Weight variation test
Percentage of
medicament test
Leaking test for
semisolid and liquid ingredients from soft capsules.
In official book, the
following quality control tests are recommended for capsules: ------
Disintegration
test:
For performing
disintegration test on capsules one capsule is placed in each tube which are
then suspended in the beakers to move up and down for 30 min. into a
thermostatically controlled fluid at 370C, unless otherwise stated in the
monograph. To fully satisfy the test, the capsules disintegrate completely into
a soft mass having no palpably firm core and only some fragments of the gelatin
shell.
Dissolution test:
For performing the
test a suitable volume of dissolution medium like distilled water, HCl or
Phosphate buffer at a pH of 7.3 as stated in the individual monograph is filled
in the glass vessel which is submerged in the water bath maintained at 370C.
The capsule to be tested in introduced in the basket and fitted in position.
The motor is started and its revolutions adjusted according to monograph. The
samples are withdrawn at specified intervals and filtered immediately through a
suitable filter medium. Generally 5ml sample solution is withdrawn each time
which is replaced with 5ml of medium at 370C in order to maintain a constant
volume in the vessel. The samples are tested by chemical analysis for
proportion of drug dissolved which should meet the requirements as stated in
the monograph.
Since the capsule
shells interfere with the analysis, the contents of a specified number of
capsules can be removed and the empty capsule shells dissolved in the
dissolution medium before proceeding with the sample in and chemical
analysis.
Weight variation
test:
For hard capsule: Ten
capsules are individually weighed and the contents removed. The emptied shells
are individually weighed and the net weight of the contents calculated by
subtraction. From the results of an assay performed as directed in the
individual monograph, the content of active ingredient in each of the capsules
is determined. The capsules pass the test if the weight of individual capsule
falls within 90-110% of the average weight. If this requirement is not met,
then the weight of the contents for each individual capsule is determined and
compared with the average weight of contents.
For soft capsule: The
gross weight of 10 intact capsules is determined individually. Then the
contents are removed by squeezing the shells which has been carefully cut. The
remainder contents are removed by washing with a suitable solvent. The solvent
is allowed to evaporate at room temperature over a period of about 30 min.,
taking precautions to avoid uptake or loss of moisture. The individual shells
are weighed and the net contents calculated. The requirements are not if:
--------
Not more than 2 of
the differences are greater than 10% of the average net content
In no case the
difference is greater than 25%
Content uniformity
test:
The requirements for
dosage uniformity are met if the amount of active ingredient is not less than 9
of the 10 dosage units as determined from the weight variation or the content
uniformity method lies within the range 8.5 – 115% of labeled amounts and no unit
is outside the range of 75 – 125% of the labeled amount and the relative
standard deviation of the 10 dosage is ( 6.
If 2 to 3 capsules of
those 10 capsules have the content range outside of 85 – 115% of labeled amount
but not outside the range of 75 – 125% or relative standard deviation are
greater than 6X, test 20 additional capsules in the same manner further.
If not grater than 3
of 30 capsules outside the range of 85 – 115% and not outside the range of 75 –
125% and RSD of 30 capsules dose not exceed 7.8%.
Moisture permeation
test:
The USP requires
determination of the moisture permeation characteristics of single unit and
unit dose containers to assure their suitability for packaging capsules. The
degree and rate of moisture penetration is determined by packaging the dosage
unit together with a color revealing desiccant pellet. For perform this test.
exposed the packaged unit to known relative humidity over a specified time and
observed the desiccant pellet for color change and compared the pre- and post-
weight of the packaged unit.
Microencapsulation:
Microencapsulation is
a process by which solids, liquids or even gases may be encapsulated into
microscopic size ranging from several tenths of 1( to 5000( in size through the
formation of thin coatings of wall material around the substance being
encapsulated. Microencapsulation provides the means: --------
Of converting liquids
to solids
Of altering colloidal
and surface properties
Of providing
environmental protection
Of controlling the
release characteristics or availability of coated materials.
Applications:
Microencapsulation is used: ----------
For masking the taste
of bitter drugs. (Acetaminophen Tab.)
To facilitate
selective sorption. (adsorbent activated charcoal)
To prepare sustained
action dosage forms. (Progesterone)
To reduce gastric
irritation. (KCl)
For separating the
incompatible ingredients. (Aspirin Tab.)
To prevent
volatilization of volatile substances. (Menthol)
In permselectivity of
enzyme, substrate and reaction products. (Urease)
To protect drugs from
moisture and oxidation. (Vit. A palmetate)
In stabilization by
conversion of dosage form i.e. liquid to solid. (Liquid crystals)
In new formulation
concepts for creams, ointments, aerosols, dressings, plasters, suppositories
and injectables.
In various
pharmaceutical related areas such as hygiene, diagnostic aids and medical
equipment design.
Disadvantages:
Incomplete or
discontinuous coating.
Inadequate stability
or shelf life of sensitive pharmaceuticals.
Non-reproducible and
unstable release characteristics of coated products.
Economic
limitations.
Factors considering
Microencapsulation:
Microencapsulation
involves a basic understanding of the general properties of microcapsules, such
as: --------
The nature of the
core and coating materials
Stability and release
of coating materials
Methodology of
microencapsulation.
Nature of the core
and coating materials:
Core Materials:
Core material is
nothing but specific material to be coated, can be liquid or solid in nature.
Liquid core can be dispensed or dissolved material. The solid core can be a
mixture of active constituents, stabilizers, diluents, excipient and release
rate retardants or accelerators.
Core material
Characteristics
Purpose of
encapsulation
Dosage form
Acetaminophen
Slightly H2O soluble
solid
Taste masking
Tablet
Activated charcoal
Adsorbent
Selective sorption
Dry powder
Aspirin
Slightly H2O soluble
solid
Separation of
incompatibles
Tablet Capsule
Islet of Langerhans
Viable cells
Sustained
normalization of diabetic condition
Injectable
Isosorbide dinitrate
H2O soluble solid
Sustained release
Capsule
Liquid crystals
Liquid
Conversion of liquid
or solid: stabilization
Menthol
Volatile solution
Reduction of
volatility
Lotion
Progesterone
Slightly H2O soluble
solid
Sustained release
Varied
KCl
Highly H2O soluble
solid
Reduced gastric
irritation
Capsule
Urease
H2O soluble enzyme
Permselectivity of
enzyme, substrate and reaction products.
Dispersion
Vitamin A palmitate
Non volatile liquid
Stabilization to
oxidation
Dry powder
Coating Materials:
Typical coating
properties such as cohesiveness, permeability, moisture sorption, solubility,
stability and clarity must be considered in the selection of the proper
microcapsule coating material.
Criteria: The coating
materials should: -------
Be capable of forming
a film that is cohesive with the core material
Be chemically compatible
Non reactive with the
core material
Provide the desired
coating properties such as strength, flexibility, impermeability, optical
properties and stability.
Coating materials
used in microencapsulation:
Water soluble resins:
Gelatin, Starch, Polyvinylpyrrolidone, Carboxymethylcellulose, Methylcellulose,
Polyvinyl alcohol and Polyacrylic acid.
Water insoluble
resins: Ethylcellulose, Polyethylene, Polymethacrylate, Polyamide,
Ethylene-Venyl acetate, silicones and cellulose nitrate.
Waxes and lipids:
Paraffin, Beeswax, Stearic acid, Stearyl alcohol and Glyceryl stearates.
Enteric resins:
Shellac, Cellulose acetate phthalate and Zein.
Stability and release
of core materials:
Three important
fields of current microencapsulation application are: --------.
The stabilization of
core materials: Microencapsulated Vit. A palmitate remains stable for a long
period of time when preserved in 450C at 75% R.H. On the otherhand,
un-capsulated Vit. A palmitate loses stability within 7 – 15 days when
preserved in 450C at 75% R.H.
The release of core
materials: Release of core materials depends on the following factors:
---------
The permeability of
the coating to the extraction fluid.
The permselectivity,
if any, of the coating to core material solute.
The dissolution rate
of the core material
The coating thickness
The concentration
gradient existing across the coating membrane.
The release of core
material or disruption of the coating can occur by pressure, shear or abrasion
forces, any of which affords a release mechanism. Two release characteristics
are illustrated as: ---------
Release of aspirin is
accomplished by a leaching or diffusion mechanism from the inert, pH
insensitive ethyl cellulose coating.
Release of
amphetamine is accomplished initially be a leaching action from the gastric
fluid resistant coating then by the action of intestinal fluid in which the
coating dissolves or disintegration.
C. Separation of
chemically reactive ingredients within a tablet or powder mixture.
Methodology of
microencapsulation:
Microencapsulation
Processes and their Applicabilities
Microencapsulation
process
Applicable core
material
Approx. particle
size. ((m)
Air suspension
Solids
35 – 5000
Coacervation-phase
separation
Solids & liquids
2 – 5000
Multiorifice
centrifugal
Solids & liquids
1 – 5000
Pan coating
Solids
600 – 5000
Solvent evaporation
Solids & liquids
5 - 5000
Spray drying &
congealing
Solids & liquids
600
Air Suspension
Method:
Microencapsulation by
air suspension techniques is generally ascribed to the inventions of Professor
Dale E. Wurster during his tenure at the University of Wisconsin
The dispersing of solid,
particulate core materials in a supporting air stream
The spray coating of
the air suspended particles.
The design of the
chamber and its operating parameters effect a re-circulating flow of the
particles through the coating zone portion of the chamber, where a coating
material, usually a polymer solution, is spray applied to the moving particles.
Mechanism of action:
Within the coating
chamber, particles are suspended on an upward moving air stream. During each
pass through the coating zone, the core material receives in increment of
coating material.
The cyclic process is
repeated, depending on the purpose of microencapsulation, the coating thickness
desired or whether the core material particles are thoroughly encapsulated.
The supporting air
stream also serves to dry the product while it is being encapsulated. Drying
rates are directly related to the volume temperature of the supporting air
stream.
Factors:
The following
variables must be considered for efficient, effective encapsulation by air
suspension techniques: ---
Density, Surface
area, Melting point, Solubility, Friability, Volatility, Crystallinity and
Flowability of the core material.
Coating material
concentration
Coating material
application rate.
Volume of air
required to support and fluidizes the core material.
Amount of coating
material required
Inlet and outlet
operating temperatures.
Advantages:
Big candidates for
microencapsulation.
The process has the
capability of applying coatings in the form of solvent solutions, aqueous
solutions, emulsions, dispersions or hot melts in equipment ranging in
capacities from 1 to 990 pounds.
This technique is
applicable to both microencapsulation and macroencapsulation coating processes.
Under idealized
conditions, particles as small as 37( can be effectively encapsulated as single
entities by this process.
Core materials
comprised of micron or submicron particles can be effectively encapsulated by air
suspension techniques.
Disadvantages:
Generally the process
is to be applicable only to the encapsulation of solid core materials.
Agglomeration of the
particles to some larger size is normally achieved.
Coacervation – Phase
Separation:
Coacervation may be
defined as a process that when solutions of two hydrophilic colloids are mixed
under suitable conditions separation of liquid phase takes phase. This process
consists of three steps: ------------
Formation of three
immiscible phases
Deposition of the
coating material on the core.
Rigidization of the
coating.
Mechanism of action:
Three immiscible
chemical phases which are formed mention below: -------
A liquid
manufacturing vehicle phase.
A core material phase
A coating material phase.
To form the three phases, the core
material is dispersed in a solution of the coating polymer, the solvent for the
polymer being the liquid manufacturing vehicle phase. The coating material
phase, an immiscible polymer in a liquid state, is formed by utilizing one of
the methods of phase separation coacervation, i.e.: ---
By changing the
temperature of the polymer solution
By adding a salt
By adding a
non-solvent
By adding
incompatible polymer to the polymer solution
By inducing a
polymer-polymer interaction.
Depositing the liquid
polymer coating upon the core material is accomplished by controlled, physical
mixing of the coating material and the core material in the manufacturing
vehicle. Deposition of the liquid polymer coating around the core material
occurs if the polymer is adsorbed at the interface formed between the core
material and the liquid vehicle phase. The continued deposition of the coating
material is promoted: ----
By a reduction in the
total free interfacial energy of the system
By the decrease of
the coating material surface area during coalescence of the liquid polymer
droplets.
Rigidizing the
coating, usually by thermal, cross linking or desolvation techniques, to form a
self sustaining microcapsule.
After complete
process i.e. separation from the liquid manufacturing, vehicle and drying, the
material appears as free flowing powder, which can be compressed as tablets,
filled in hard gelatin capsules, suspended in a suitable liquid to from a
suspension or may be converted into any other dosage form.
Some examples of Hard
and Soft gelatin capsule available in local market
Hard gelatin capsule
Brands
Generic names
Company
Indoxyl( 25mg
Indomethacin BP
Jayson pharmaceutical
Ltd.
Jmycin( 250mg
Tetracycline HCl BP
Jayson pharmaceutical
Ltd.
Ficlox
(Cloxacillin 500mg
Fisons (BD) Ltd.
Acmecilin
(Ampicillin 250mg
Acme laboratories
Ltd.
B-50 Forte
(Vitamin B complex
Square pharmaceutical
Ltd.
Soft gelatin capsule
Ratinol Forte
(Vitamin A 50000
Drug international
Vitamin A Forte
(Vitamin A 2 lac
Drug international
E – cap
( - tocopherol
acetate 100mg
Drug international
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