Article ID Journal Published Year Pages File Type
2486568 Journal of Pharmaceutical Sciences 2009 12 Pages PDF
Abstract
The aim of this study was to investigate the solubility of mefenamic acid (MA), a highly cohesive, poorly water-soluble drug in a copolymer of polyoxyethylene-polyoxypropylene (Lutrol F68®), and to understand the effect drug polymer solubility has on in vitro dissolution of MA. Solid dispersions (SD) of MA were prepared by a hot melt method, using Lutrol F68® as a thermoplastic polymeric platform. High-speed differential scanning calorimetry (Hyper-DSC), Raman spectroscopy, powder X-ray diffractometry (PXRD) and hot-stage/fluorescence microscopy were used to assess the solubility of the drug in molten and solid polymer. Drug dissolution studies were subsequently conducted on single-phase solid solutions and biphasic SD using phosphate buffer pH 6.8 as dissolution media. Solubility investigations using Hyper-DSC, Raman spectroscopy and hot-stage microscopy suggested MA was soluble in molten Lutrol F68® up to a concentration of 35% (w/w). Conversely, the solubility in the solid-state matrix was limited to <15% (w/w); determined by Raman spectroscopy, PXRD and fluorescence microscopy. As expected the dissolution properties of MA were significantly influenced by the solubility of the drug in the polymer matrix. At a concentration of 10% (w/w) MA (a single phase solid solution) dissolution of MA in phosphate buffer 6.8 was rapid, whereas at a concentration of 50% (w/w) MA (biphasic SD) dissolution was significantly slower. This study has clearly demonstrated the complexity of drug-polymer binary blends and in particular defining the solubility of a drug within a polymeric platform. Moreover, this investigation has demonstrated the significant effect drug solubility within a polymeric matrix has upon the in vitro dissolution properties of solid polymer/drug binary blends. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4545-4556, 2009
Related Topics
Health Sciences Pharmacology, Toxicology and Pharmaceutical Science Drug Discovery
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