ENHANCEMENT OF SOLUBILITY DISSOLUTION RATE AND FORMULATION DEVELOPMENT OF ACECLOFENAC TABLETS EMPOLYING β-CD AND LUTROL: A FACTORIAL STUDY

Abstract

Aceclofenac, a widely prescribed anti-inflammatory and analgesic drug belongs to class-II under BCS and exhibit low and variable oral bioavailability due to its poor aqueous solubility. As such it needs enhancement in the dissolution rate and bioavailability in their formulation development to derive its maximum therapeutic efficacy. The objective of the present study is enhancement of solubility, dissolution rate of aceclofenac, a poorly soluble BCS-Class II employing β-CD and Lutrol. The individual and combined effects of β-CD and Lutrol in enhancing the solubility and dissolution rate of aceclofenac were evaluated in a 22-factorial study. The feasibility of formulating the drug-β-CD-Lutrol solid inclusion complexes into tablets was also evaluated. Aceclofenac -β-CD-Lutrol inclusion complexes and their tablets were formulated employing selected combinations of β-CD (factor A) and Lutrol (factor B) as per 22 factorial design and were evaluated. Combination of βCD with Lutrol gave a much higher enhancement in the solubility of aceclofenac, (9.66 fold) than is possible with them alone. β CD alone gave a higher enhancement (9.7 fold) in the dissolution rate of (K1) of aceclofenac. There was no additional advantage of combining βCD and Lutrol in enhancing the dissolution rate of aceclofenac. The dissolution efficiency (DE 30) of aceclofenac was increased from 3.9 % for pure drug to 32.66, 21.36 and 24.39 % respectively with βCD, Lutrol and βCD – Lutrol complexes. Aceclofenac-βCD – Lutrol inclusion complexes could be formulated into tablets by direct compression method and the resulting tablets fulfilled the official (IP 2010) specifications with regard to drug content, hardness, friability and disintegration time. Tablets formulated employing βCD (Fa) and βCD- Lutrol (Fab) gave rapid and higher dissolution of aceclofenac, 2.26 and 1.86 fold increase in K1 when compared to formulation F1 (plain).These tablets also fulfilled the official (IP 2010) dissolution arte specification of NLT 70 % in 45 min prescribed for aceclofenac tablets. Complexation with βCD alone and in combination with Lutrol is recommended for formulation of aceclofenac tablets with fast dissolution characteristics.