Formulation and Evaluation of Ethyl Cellulose Coated Microspheres of Aceclofenac

 

SM Sarode*, MK Kale1 and G Vidyasagar2

1K.Y.D.S.C.T’s College of Pharmacy, Sakegaon (M.S.)

2Veerayatan Institute of Pharmacy, Bhuj, Gujarat.

 

ABSTRACT:

The pain is symptomatic of some form of dysfunction and resultant inflammatory processes in the body. More than 15% of the worldwide population suffers for instance from some form of osteoarthritis and this incidence is even higher in elderly. As the world population is grows older, this incidence will continue to rise. Aceclofenac has been shown to have potent analgesic and anti-inflammatory activities and due to its preferential cox-2 blockade it has better safety than conventional NSAIDs with respect to adverse effects on gastrointestinal and cardiovascular system. Ethyl cellulose microspheres of Aceclofenac were prepared by emulsion- solvent evaporation technique that is an industrially feasible technique. The microspheres are spherical, discrete and free-flowing. Encapsulation efficiency was found to be 81%. Aceclofenac release from microspheres was slow and diffusion controlled. Good liner relationships were observed between percent coat and release rate of the microspheres. These microspheres were found suitable for oral controlled release.

 

KEYWORDS: Microencapsulation, controlled release, Aceclofenac.

 

INTRODUCTION:

Drugs that are easily absorbed from the gastrointestinal tract (GIT) and having a short half-life are eliminated quickly from the blood circulation. To avoid this problem, the oral controlled release formulations have been developed, as these will release drug slowly into the GIT and maintain a constant drug concentration in the serum for a longer period of time. Microspheres have been widely accepted to achieve such an oral controlled release. These microspheres require a polymeric substance as a coat material. A number of biodegradable as well as nonbiodegradable substances have been investigated for the preparation of microspheres. Ethyl cellulose is a biocompatible, nontoxic, nonbiodegradable cellulose polymer having good film forming properties. This study describes the preparation and evaluation of ethyl cellulose microspheres of Aceclofenac with an objective to achieve controlled release over longer periods of time and to avoid gastrointestinal irritation if present in larger concentration.

 

MATERIALS AND METHOD:

Ethyl cellulose with viscosity of 22cps in a 5% concentration by weight in 80:20 toluene: ethanol solution. Aceclofenac IP was provided by Aristo pharmaceuticals, Mumbai. Dichloromethane, 0.1 N HCL, Sodium CMC .All solvents and reagents used were of AR grade. Microspheres of Aceclofenac were prepared by Emulsion Solvent evaporation method.

 

PREPARATION OF MICROSPHERES:

Ethyl cellulose (2.5g) was dissolved in dichloromethane (25ml) to form a homogenous polymer solution. Core material, Aceclofenac (1.5g) was added to the polymer solution (10ml) and mixed thoroughly. The resulting mixture was then added in a thin stream to 100ml of 0.1N HCl containing sodium CMC (0.5%w/v) contained in a 450 ml of beaker while stirring at 750 rpm to emulsify the added dispersion as fine droplets.

 

A Remi medium duty stirrer with speedometer was used for stirring. Stirring was continued for 5 minute to disperse the added mixtures as fine droplets. The solvent dichloromethane was then removed by evaporation at room temperature (28˚C) under reduced pressure to produce spherical microspheres. The microspheres were collected by vacuum filtration and washed repeatedly with water. The product was then air dried to obtain discrete microspheres.

 

Estimation of Aceclofenac:

Aceclofenac in the microspheres was estimated by an UV Spectrophotometric method based on the measurement of absorbance at 285nm in phosphate buffer of pH 7.4. The method was validated for linearity, accuracy and precision and it also obeyed Beers law in the concentration range 0-10µg/ml. A sample of microspheres equivalent to 25mg of Aceclofenac was dissolved in 25ml of ethyl alcohol and the volume was adjusted to 100ml using phosphate buffer of pH 7.4. The solution was suitably diluted and the absorbance was measured at 285nm. The drug loading and % incorporation efficiency were calculated by using equations 1 and 2, respectively.

 

Where, Mactual is the actual Aceclofenac content in weighed quantity of powder of microspheres and Mtheorotical is the theoretical amount of Aceclofenac in microspheres calculated from the quantity added in the fabrication process.

 

CHARACTERIZATION OF MICROSPHERES:

For size distribution analysis, different sizes of microspheres were separated by sieving using a range of standard sieves. The amounts retained on different sieves were weighed. Encapsulation efficiency was calculated using equation.

 

Fig.1: Release profile of Aceclofenac from EC Microspheres.

 

Scanning electron microscopy (SEM):

The surface morphology of the microspheres was examined by Scanning Electron Microscopy (SEM) (Philips, XL30). The dried microspheres were coated with a very thin coat of carbon. The size of the microspheres was measured by image analysis. During the SEM examination, an electron beam incident on the sample and interacting with a deep region of the sample causes the emission of x rays that are characteristic of the elements present in the particle and allow a qualitative analysis of its chemical composition. The electron beam is very thin, so analysis can be performed on well-defined areas of the sample.

 

Fig.2: Scanning electron micrograph of ethyl cellulose coated Microspheres.

 

Drug release studies:

Release of Aceclofenac microspheres of size 18/20 and 12/14 was studied in phosphate buffer of pH 7.4 (900ml) using an USP II dissolution rate test apparatus at 50 rpm and at 37±0.5˚C. Fig.1 shows the release profile of Aceclofenac from ethyl cellulose microspheres. A sample of microspheres equivalent to 50mg of Aceclofenac was used. Samples were withdrawn through a filter (0.45µ) at different time intervals over a period of 12 hours and were assayed at 285nm for Aceclofenac using double beam UV spectrophotometer.

 

RESULTS AND DISCUSSIONS:

Ethyl cellulose microspheres of Aceclofenac were prepared by emulsion solvent evaporation method employing dichloromethane as a solvent for the polymer. The microspheres were found to be discrete, spherical and free flowing. The size distribution of different microspheres showed that about 56% and 44% were in size range of 18/20 and 12/14-mesh size respectively. Drug content of microspheres was found to be same in different sieve fractions. Aceclofenac release from microspheres of size 18/20 and 12/14 was studied in phosphate buffer of pH 7.4 for a period of 12 hours. Aceclofenac release from all the microspheres was slow and sprayed over extended period of time. The release follows first order kinetics with ‘r’ greater than 0.956. The drug release depended on size of the microspheres and the wall thickness. Thus spherical microspheres of ethyl cellulose containing Aceclofenac were prepared by an emulsion solvent evaporation method employing dichloromethane as a solvent. Encapsulation efficiency was found to be 81%. Aceclofenac release from the microspheres was slow and extended over a period of 12 hours. Drug releases was diffusion controlled and follow zero order kinetics. Thus the ethyl cellulose microspheres were found suitable for oral controlled release. Fig.2 shows a SEM image of ethyl cellulose coated aceclofenac microsphere produced by the solvent evaporation technique.

 

ACKNOWLEDGEMENTS:

Authors are thankful to I.I.T. Powai for SEM Studies.

 

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Received on 29.09.2009

Accepted on 20.11.2009        

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Research Journal of Pharmaceutical Dosage Forms and Technology. 2(1): Jan. –Feb. 2010, 41-43