Abstract

FORMULATION AND EVALUATION OF SUSTAINED RELEASE MICROSPHERES RESIN LOADED ACELOFENAC

Dr. Praveen Ashok, Dr. Yogita Tyagi, Ms Hiba Parveen and Vikash Kumar*

Abstract

Adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs) are seen in almost all organs but GI tract is most frequently affected as they cause GI irritation, bleeding and also peptic as well as duodenal ulceration. Concepts about gastro-duodenal mucosal ulceration have been evolved from the simple theory of topical injury to other theories involving multiple mechanisms with both local and systemic effects. Aceclofenac is one of the commonly used NSAIDs. It belongs to class II drugs in BCS and characterized by poor aqueous solubility and high absorption. Dissolution of aceclofenac is a rate limiting step which affects its onset especially in dental pain, rheumatoid and osteoarthritis. Solid dispersion is a type of solid state material where molecular dispersion of one or more active drugs is carried by an inert carrier. The above mentioned considerations led to the objective of this study, which aimed to prepare and evaluate solid dispersion systems containing aceclofenac and Eudragit Ll00, Eudragit S100, Eudragit RL100, PVP k90 and methyl cellulose 15cps. All formulations were prepared by dissolving the polymer in a mixture of isopropanol and acetone (1:1 V/V), 100mg drug was then dissolved in a minimal amount of the solvents mixture at 40oC. Solvent were evaporated over a period of 24 hrs under stirring conditions (150 rpm) at room temperature, 1:1. 1:2 and 1:3 ratios were utilized for each polymer. The polymer which showed the optimum release conditions was chosen for in-vivo studies using male Wistar rats. The obtained solid dispersion systems were evaluated using FT-IR, DSC and PXRD. Drug content as well as in- vitro drug release studies were determined at different pH values. Drug content in the prepared matrices ranged between 97.98% and 100%. No significant drug-polymer interactions were observed in IR studies. Aceclofenac entrapment efficiency in the different prepared formulations was affected by neither the polymer type nor drug to polymer ratio. Solid dispersion with Eud S100 1:1 drug to polymer significantly reduced gastric irritations and gastric ulcers compared to free drug as well as the other proposed formulations as proved from histopathological examination of rat stomachs.

Keywords: Solid dispersion; Aceclofenac; NSAIDs; Drug delivery systems; Ulcerogenic activity.