title: Characterisation of the thermal, spectroscopic and drug dissolution properties of mefenamic acid and polyoxyethylene-polyoxypropylene solid dispersions.
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.
authors.affiliation: The Drug Delivery and Biomaterials Research Group, School of Pharmacy, Medical Biology Centre, Queen's University, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK. g.andrews@qub.ac.uk
authors.forename: Gavin P
authors.initials: GP
authors.lastname: Andrews
authors.forename: Hui
authors.initials: H
authors.lastname: Zhai
authors.forename: Simon
authors.initials: S
authors.lastname: Tipping
authors.forename: David S
authors.initials: DS
authors.lastname: Jones
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D008528:Mefenamic Acid / Q000737:chemistry*; D008856:Microscopy, Fluorescence; D011060:Poloxalene; D012995:Solubility; D013059:Spectrum Analysis, Raman; D013816:Thermodynamics; D014961:X-Ray Diffraction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D008528:Mefenamic Acid; D011060:Poloxalene