microcapsules F

Contents
1. Introduction
2. Reasons for Microencapsulation
3. Types of microcapsules
4. Formulation considerations
5. Techniques for preparation of microcapsules
6. Evaluation of microcapsules
7. Applications of microcapsules in pharmacy
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Introduction
• Microencapsulation is the process of enclosing a substance
inside a miniature called capsule.
• Microcapsules are a small sphere with a uniform wall around
it. The material inside the microcapsule is referred to as the
core/ internal phase, whereas the wall is sometimes called a
shell/coating.
• The microcapsule size range from 1 µ -7mm. All the 3 states
i.e. solid, liquid and gases may be encapsulated which may
affect the size and shape of capsules.
• If the solid or crystalline material is used as the core, the resultant capsule may be irregularly
shaped.
• If the core material is liquid, simple spherical capsules containing a single droplet of encapsulate
may be formed.

Reasons for Microencapsulation
• It is mainly used to increase the stability, and sustained/prolonged release of the product.
• Controlling the release rate of the drug from the microcapsules.
• This technique was widely used for masking taste and odor of many drugs and to improve patient
compliance.
• For converting liquid drugs into a free flowing powder.
• To reduce the toxicity and GI irritation and many major side effects of the drugs.
• Alteration in site of absorption can be achieved by microencapsulation.
• In some cases, the core must be isolated from its surroundings, as in isolating vitamins from the
deteriorating effects of oxygen.
• In retarding evaporation of a volatile core.
• To improve handling properties of a sticky material.
• To protect the GIT from irritant effects of drug, for example aspirin.

Types of microcapsules
1. Mononuclear (core-shell) microcapsules contain the shell around the core.
2. Polynuclear capsules have many cores enclosed within the shell.
3. Matrix encapsulation in which the core material is distributed homogeneously into the shell material.

Formulation considerations
1. Core material: The core material is defined as the specific material to be coated whether it can be a
solid or liquid. The solid core can be the active ingredient, stabilizers, diluents, excipients, release rate
retardants whereas liquid core include the dissolved materials.
2. Coating material: Coating materials are defined as a layer of substance covered over the core for
production of the drug. The coating material should possess properties such as
• It should have controlled release under specific conditions, soluble in aqueous media/solvent.
• It should possess sufficient properties such as flexibility, strength, impermeability, stability and optical
properties.
• It should be chemically compatible with the core and non-reactive.
• It should be capable of forming a film.

List of coating materials
Water soluble resin Water insoluble resin Wax and lipid Enteric resin
Gelatin Ethyl cellulose Paraffin Shellac
Gum Arabic Polyethylene Carnauba wax Zein
Polyvinyl pyrrolidone Polymethacrylate Bees wax Cellulose acetate
phthalate
Carboxy methyl cellulose Cellulose nitrate Stearic acid
Methyl cellulose Silicones Stearyl alcohol
Arabinogalactan
Polyvinyl acrylate

Properties of some microencapsulated core materials
Core material
Aspirin
Characteristic
property
Slightly water
soluble solid
Purpose of encapsulation
Taste masking; sustained release;
reduced gastric irritation,
separation of incompatibilities
Final product form
Tablet or capsule
Vitamin A palmitate Non volatile liquid Stabilization to oxidation Dry powder
Isosorbide dinitrate Water soluble solid Sustained release capsule

Techniques for preparation of microcapsules
Microencapsulation techniques
Physical methods Chemical methods Physicochemical methods

1. Physical Methods
A. Air suspension coating: In this method the core material
which is a solid is dispersed into supporting air stream and
these suspended particles of drug coated with polymers in
volatile solvent release leaving a very thin layer/film of a
polymer on core. The process is repeated for several times
until required parameters such as coating thickness are
achieved. The air stream which supports particles also helps
to dry the particles. The rate of drying is directly
proportional to the temperature of air stream. The coating
chamber is arranged such that particles move upwards through coating zone, then disperse into moving
air and back to the base of coating chamber making repeated passes until desired thickness is achieved.

B. Coacervation process: In this process, the
core material is dispersed in the solution of
coating material such that the Core material
doesn’t dissolve/react in solvent.
Coacervation occurs when there is a change
of pH value of the dispersion which is done
either by adding sulphuric acid, Hcl, organic
acids as a result it decreases the solubility of
the
dispersed phase (shell material) and proceeds to form precipitate from the solution. The shell material forms
a continuous coating around core and shell cools down to harden and forms a microcapsule. The hardening
agents such as formaldehyde may be added to the process. The suspension was then dried in spray drier /
fluidized bed dryer.

C. Pan coating: It is the one of the oldest method used in pharmaceutical industry. In this method, the
particles are tumbled in a pan while the coating material is applied slowly. The solution is applied from the
atomized spray to the core material, hot air is passed to remove coating solvent. Particles > 600µm in size
are essentially effective for pan coating.

D. Spray drying and congealing method: This method is suitable for
labile drugs because of less contact time in dryer & it is
economical. In this process active material is dissolved/suspended
in polymer solution and trapped in the dried particle. Both the
methods are similar in process of dispersion of core & coating
substance but there is a difference in rate of solidification of
coating. In spray drying, there is a rapid evaporation of solvent in
which coating material is dissolved whereas in case of spray
congealing solidifying occurs by thermal congealing/introducing a
non solvent. Removal of non solvent is by sorption, extraction and
evaporation.
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2. Chemical Methods
Solvent evaporation method: This method is widely
used for water soluble and water insoluble materials
to produce solid and liquid core materials. A variety
of film forming agents or polymers can be used. In
this method, the coating material (polymer) is
dissolved in a volatile solvent which is immiscible
with the liquid vehicle phase. A core material (drug)
which is to be microencapsulated is dissolved or
dispersed in the coating polymer solution. With
agitation, the core coating material mixture or
dispersion is dispersed in the liquid manufacturing
vehicle phase to obtain the appropriate size
microcapsule. The solvent is evaporated either by
continuous agitation or by application of external
heat supply.

3. Physico-chemical Methods
Coacervation phase separation:
• Coacervation means the separation of a liquid or phase when solution of two hydrophilic colloids are
mixed under suitable conditions.
• In this method, the three immiscible phases of core material, solvent and coating material are formed
followed by deposition of coating material on the core.
• The coating material is dissolved in a suitable solvent and the core material is uniformly dispersed in the
solution of the coating material.
• Then the coating material is phased out of its solution which starts getting deposited on the particles of
the core material.
Coat formation during coacervation-phase separation process consists of three steps carried out under
continues agitation
i. Formation of 3 immiscible phases (core material, coating material phase, liquid phase).
ii. Deposition of polymer on core material.
iii. Rigorization of coating material.

Phase separation can be achieved by-
1. Temperature change
2. Incompatible polymer addition
3. Non-solvent addition
4. Salt addition
5. Polymer-polymer interaction

Evaluation of microcapsules
Percentage Yield-
The total amount of microcapsules obtained was weighed and the percentage yield calculated taking into
consideration the weight of the drug and polymer.
“Percentage yield = Amount of microcapsule obtained / Theoretical Amount×100”
Scanning electron microscopy-
• Scanning electron photomicrographs of drug loaded with polymer, microcapsules were taken. A small
amount of microcapsules was spread on gold stub and was placed in the scanning electron microscopy
(SEM) chamber.
• The SEM photomicrographs are taken at the acceleration voltage of 20 KV.
Encapsulation efficiency-
Encapsulation efficiency was calculated using the formula:
“Encapsulation efficiency = Actual Drug Content / Theoretical Drug Content ×100”

Particle size analysis-
For size distribution analysis, different sizes in a batch were separated by sieving by using a set of standard
sieves. The amounts retained on different sieves were weighed.
Invitro Drug release Studies-
Drug release was studied by using USP type II dissolution test apparatus in Phosphate buffer of pH 7.4 (900
ml). The paddle speed at 100 rpm and bath temperature at 37 ± 0.5°c were maintained through out the
experiment. A sample of microcapsules was used in each test. Aliquot equal to 5ml of dissolution medium
was withdrawn at specific time interval and replaced with fresh medium to maintain sink condition. Sample
was filtered through Whatman No. 1 filter paper and after suitable dilution with medium; the absorbance
was determined by UV spectrophotometer at specific wavelength. All studies were conducted in triplicate
(n=3). The release of drug from marketed sustained release tablet was also studied to compare with
release from microcapsules.

Applications of microcapsules in pharmacy
• To improve the flow properties. e.g. Thiamine, Riboflavin
• To enhance the stability. e.g. Vitamins
• To avoid incompatibilities. e.g. Aspirin and Chloramphenicol
• To convert liquids into solids. e.g. Castor oil, Eprazinone
• To reduce gastric irritation. e.g. Nitrofurantoin, Indomethacin
• To reduce the volatility of materials. e.g. Peppermint oil, Methyl salicylate
• To mask the unpleasant taste and odor. e.g. Aminophylline, castor oil
• Microencapsulation has been employed to provide protection to the core materials
against atmospheric effects, e.g., Vitamin A Palmitate.
• Separation of incompatible substance has been achieved by encapsulation
• To mask the bitter taste of drugs like Paracetamol, Nitrofurantoin etc.
• To reduce gastric and other gastro intestinal (G.I) tract irritations, For e.g., sustained
release Aspirin preparations have been reported to cause significantly less G.I. bleeding
than conventional preparations.

• A liquid can be converted to a pseudo-solid for easy handling and storage. e.g. Eprazinone.
• Hygroscopic properties of core materials may be reduced by microencapsulation e.g. Sodium
chloride.
• Carbon tetra chlorides and a number of other substances have been microencapsulated to reduce
their odor and volatility
• To reduce volatility of liquids like peppermint oil
• Helps to prepare SRDF and enteric coated products, controlled release products
• Used to improve flow properties before compression into tablets
Brand name API Manufacturer
ReGel (oncogel) Paclitaxel Macro Med Inc.
Clopidogrel Clopidogrel + Aspirin Lupin pinnacle
Clobitab Clopidogrel + Aspirin Lupin pinnacle
Atoplus Atorvastatin Triton (calyx)
Some examples of marketed formulations of microcapsules.