Background: The present work describes the role of melt granulation and microenviron-mental
pH modulation technique in solubility enhancement of a poorly water soluble NSAID, Aceclofenac
(ACL). ACL is a BCS Class II drug showing dissolution rate limited absorption and pH dependent
solubility, with higher solubility at alkaline pH. The limited solubility of ACL affects drug absorption
and hence, therapeutic effect as the drug is indicated in conditions of pain where rapid onset of action
Methods: Solubility enhancement of ACL was carried out by melt granulation technique using
Gelucire 50/13 as molten carrier. The solubility of ACL was improved further by incorporating sodium
hydrogen carbonate as pH modifier. The granules of ACL thus developed, were compressed into
tablets using adsorbing carriers and other tableting excipients.
Results: This dual approach not only enhanced ACL solubility but also aided in achieving a pH
independent release. The developed tablets exhibited pH independent release as well as enhanced rate
of dissolution which is indicated by in vitro dissolution studies and ex-vivo intestinal permeation
studies. The pH independent release would ensure absorption of drug throughout the gastrointestinal
tract. The solubility enhancement of ACL was further confirmed by characterization studies such as
DSC and XRD.
Conclusion: Thus, the dual approach of melt granulation and micro-environmental pH modulation can
be simple and scalable method for solubility enhancement of poorly soluble drugs showing pH
dependent dissolution rate limited absorption.