EVALUATION OF

MICROENCAPSULATION

PRESENTED BY :_

MR. ANURAG PDY (B.PHARM)

SUBMITTED TO :_

MR.VIPIN AGARWAL

ASSOCIATE PROFESSOR

AT

(INVERTIS INSTITUTE OF PHARMACY)

INTRODUCTIONMicroencapsulation is one of the most interesting modes of drug delivery systems.

It is an interdisciplinary field that requires knowledge of field of pure polymer science, familiarity in emulsion

technology and an in-depth understanding of drug and protein stabilization.

It is a process in which very tiny droplets or particles of liquid or solid material are surrounded or coated with a

continuous film of polymeric material, ranging in size from 1 to 5,000 microns.

This technique is mainly used for taste masking of bitter drugs, formulation of controlled release and sustained

action dosage forms, separation of incompatible materials, protection of moisture and light sensitive drugs.

Diclofenac sodium (DS) is a Non-steroidal anti-inflammatory drug (NSAID) belongs to the group of aryl acetic acid

derivative.

It is widely used in treatment of rheumatoid arthritis, osteoarthritis and ankylosing spondylitis.

Because of its short biological half-life (2 hrs.), it is eliminated from plasma compartments of the body within few

hours, so frequent administration is necessary to maintain its therapeutic concentration.

Evaluation of sustained release

microcapsules containing Diclofenac sodium

(Continued…….)

It also known that repeated oral administration of DS in the large doses causes gastrointestinal disturbances,

peptic ulcer and bleeding.

The usual therapeutic dose and dosing frequency of conventional DS tablets is high, because of the short

biological half-life of the drug (2 hrs.); makes it an ideal candidate for modified release dosage forms.

To reduce the frequency of administrations and to improve patient compliances, once daily sustained release

dosage forms of DS is desirable.

The choice of the methods for the preparation of microcapsules depends on many factors such as the drug

solubility, partition co-efficiency, polymer composition, molecular weight etc.

For instance, emulsion solvent evaporation technique may be a method of choice for the preparation of

microspheres of water insoluble drugs.

In the emulsion solvent evaporation method, the water insoluble drug and polymer are dissolved in an organic

phase, emulsified to form an o/w emulsion, evaporated the organic phase and the microcapsules so formed are

filtered and dried.

Since Diclofenac is a water insoluble drug, emulsion solvent evaporation technique is selected for the preparation

of sustained release microcapsules

2. MATERIALS AND METHODS

2.1. Materials

Ethyl cellulose, sodium carboxyl methyl cellulose, chloroform, hydrochloric acid and methanol.

All reagents used were of analytical reagent grade.

Double distilled water was used for all the experiments.

2.2. Preparation of DS microcapsules

DS microcapsules were prepared by emulsion solvent evaporation technique by employing the

chloroform as solvent and ethyl cellulose as a polymer with a core: coat ratio of 1:1, 2:3 and 2:1.

The polymer (1, 1.5 and 0.5 g) was dissolved in chloroform (25 mL) to form a homogeneous

polymer solution.

Core material DS (1 g) was added to the polymer solution and mixed thoroughly.

The resulting solution was then added in a thin stream to 100 mL of 0.1N HCl containing 1% w/v

sodium carboxyl methylcellulose contained in a 250 mL beaker while stirring at 600 rpm to emulsify

the added droplets.

Stirring was continued for 10 min to disperse the added mixture as fine droplets.

The dispersion was transferred to a Buchner flask and stirring was continued with laboratory stirrer.

The solvent was then removed by evaporation at room temperature to produce spherical

microcapsules.

The microcapsules were collected by decantation and washed with water.

The product was then dried at 600 C for 1 h to get discrete microcapsules.

2.3. Characterization of DS microcapsules

2.3.1. Particle Size Distribution

Different sizes of microcapsules in a batch were separated by sieve analysis [11] using a range of standard

sieves (#10, #22, #44, #52 and # 60). The amount retained on different sieves was weighed. From the

obtained data, weight percent retained on different sieves and average size of microcapsules were

calculated.

2.3.2. Shape and surface morphology

The shape and surface morphology of the microcapsules

was studied by using scanning electron microscope. Microcapsules were mounted directly onto the SEM

sample stub using double-sided sticking tape and coated with gold film (thickness 200 nm) under reduced

pressure (0.001 mm of Hg).

2.3.3. Practical yield

The percentage yield of DS in the microencapsulated

product is determined by using the formula,

2.3.4. Percentage drug content

Microcapsules equivalent to 50 mg of DS were weighed accurately and dissolved in the 10 ml of

chloroform. The solution was filtered, diluted suitably and drug content was analyzed at 285 nm by UV

spectrophotometer. Each sample analyzed in triplicate. Percentage drug content was calculated for all

batches using the equation as follows:

2.3.5. Encapsulation efficiency

The encapsulation efficiency of microcapsules was

Calculated by using the formula:

2.3.6. In vitro drug release studies

In vitro release profile for microcapsules as well as pure drug were performed using USP XXII type 2

dissolution apparatus. Sample equivalent to 100 mg of Diclofenac was added to 900mL phosphate buffer of

pH 7.4 at 37±0.5ºC and stirred at 50 rpm. Aliquot of 5 mL was withdrawn at time intervals of 0.25, 0.5,

0.75, 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 h. The with drawn volume was replenished with the same volume of

dissolution medium in order to keep the total volume constant. The absorbance of the samples was

measured at λ max 285 nm after suitable dilution if necessary, using phosphate buffer of pH 7.4 as blank.

Results of in vitro drug release studies obtained from absorbance data were tabulated and shown

graphically as Cumulative % drug released V/s Time.

* The percentage practical yield decreased as the concentration of polymer

increased in the formulation. The percentage practical yield was found to be in

the range of 62.84 to 80.85 %. The maximum percentage practical yield was

found to be 80.85% for F-1. The microcapsules of all three batches were found

to be discrete, spherical, free-flowing and of uniform in size. The average size

of microcapsules in various batches was found to be 759.12 μm, 669.97 μm and

758.7 μm for F-1, F-2 and F-3, respectively.

3. RESULTS AND DISCUSSION

4. CONCLUSIONS

Sustained release DS microcapsules could be formulated by

using ethyl cellulose as a release retardant by emulsion solvent

evaporation technique.

The microcapsules of all the formulated batches were spherical,

discrete and free flowing.

The drug content was found to be uniform in a batch of

microcapsules.

Increasing the polymer concentration in microcapsule

formulation decreases the rate of drug release dramatically.

Further, an elaborate in vivo study is to be carried out for the

formulated microcapsule using a suitable animal model.

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