Dissolution enhancement of indomethacin-chitosan hydrochloride composite particles produced using supercritical assisted atomization

This study investigated the formation of drug-carrier composite particles via a supercritical assisted atomization (SAA) process using 50% (v/v) aqueous ethanol as a solvent, and carbon dioxide as a spraying medium. Indomethacin (IMC), a poorly water-soluble drug, was used as a model drug and chitosan hydrochloride (CH), a water-soluble carrier, was used as a carrier for composite particles. The effects of size and different CH to IMC weight ratios in the composite particles on drug dissolution rate were investigated. XRD, DSC and FTIR analyses showed that the SAA-treated IMC transformed from gamma-form (as received IMC) to the meta-stable alpha-form. In vitro dissolution test showed that the IMC dissolution rate was enhanced because of the transformation in crystalline form, increased drug wettability due to water-soluble CH in composite particles, and high surface area due to the decreased size of composite particles. Furthermore, the composite particles demonstrated enhanced drug permeability in Caco-2 cell monolayer. Taken together, the enhanced permeability and dissolution rate could be beneficial for the bioavailability of active pharmaceutical ingredients (APIs). (C) 2016 Taiwan Institute of Chemical Engineers. Published by Elsevier B.V. All rights reserved.