Preparation, characterization and improved release profile of ibuprofen-phospholipid association

Abstract

Ibuprofen is a widely prescribed non-steroidal and anti-inflammatory drug, which is practically insoluble in water and causes gastrointestinal (GI) side effects. Ibuprofen-phosphathidylcholine association (IPA) was prepared by refluxing ibuprofen and phosphathidylcholine in three different molar ratios (1:0.25, 1:0.5 and 1:1) in aim to induce the amorphous nature of ibuprofen and increase its solubility. The characteristics of IPA were evaluated by H1-NMR, FT-IR spectra, X ray diffraction (XRD), differential scanning calorimetry (DSC), drug content, photon correlation spectroscopy, computational molecular simulation, solubility and in vitro dissolution study. Computational molecular simulation, DSC, FT-IR, H1-NMR and XRD patterns confirmed the reaction between carboxyl group of ibuprofen and polar moiety of phosphathidylcholine. IPAs showed an increase in solubility in phosphate buffer medium (pH 7.2) and a decrease in solubility in HCl medium (pH 1.2). The IPA dissolution rate increased in the simulated intestinal medium, whereas the dissolution rate of the IPA decreased in the simulated gastric medium. It is concluded that the phosphatidylcholine association of ibuprofen may be of potential use for improving the ibuprofen solubility and hence its bioavailability. Furthermore, considering decrease of dissolution rate of IPA in acidic medium, it may also reduce GI toxicity of ibuprofen. Moreover, comparing different molar ratios of IPA, there is no significant difference in their characteristics and dissolution profiles.