Solubility and Dissolution enhancement of poorly water soluble drug Aceclofenac by solid dispersion method

Abstract

Aceclofenac is a novel non-steroidal anti-inflammatory drug (BCS-class II) having anti-inflammatory and analgesic properties, and is widely used in the treatment of rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. One of the major problems with this drug is its low solubility in biological fluids, which results into poor bioavailability after oral administration. So the objective of present work is to improve the solubility and dissolution rate of Aceclofenac using its solid dispersions (SDs) with β-Cyclodextrin. Inclusion complex of Aceclofenac with β- Cyclodextrin was prepared by physical mixture, co-grinding and kneading method at 1:1 w/w ratio. It was clear that kneading method would be the best method for the preparation of inclusion complex of Aceclofenac with β-CD. Hence Kneading method was selected for further study (K1, K2, K3 & K4 in 1:0.5, 1:1, 1:1.5 & 1:2 ratios respectively). Phase solubility study was conducted to evaluate the effect of polymer on aqueous solubility of Aceclofenac. The In vitrodissolution studies were carried in pH 6.8, higher in vitrodissolution of solid dispersions was recorded compared to their corresponding physical mixtures and the pure drug. The prepared solid dispersions were observed that increased in the saturation solubility and dissolution rate of Aceclofenac than that of pure drug. Aceclofenac: β-CD in 1: 2 drug to carrier ratio exhibited the highest drug release (68.13 in 120sec). The FT-IR study and differential scanning calorimetry (DSC) shows that drug was stable in solid dispersions and there were no interactions. It is concluded that dissolution rate was improved by solid dispersion of Aceclofenac-CD prepared as 1:2 ratio showed excellent physicochemical characteristics and was found to be described by dissolution release kinetics and was selected as the best formulation.