Solid Dispersion Approach Improving Dissolution Rate of Stiripentol: a Novel Antiepileptic Drug

Abstract

Some drugs have low bioavailability due to their poor aqueous solubility and/or slowdissolution rate in biological fluids. Stiripentol (STP) is a novel anticonvulsant drug that isstructurally unrelated to the currently available antiepileptics. It has poor aqueous solubilityand its solubility has to be enhanced accordingly. Polyethyleneglycol 6000 (PEG-6000) iscommonly utilized as a hydrophilic carrier for poorly water soluble drugs in order to improvetheir bioavailability. STP and PEG-6000 binary system was obtained by physical mixture,solvent evaporation, co-evaporation and melting methods using different weight ratios.The properties of the prepared binary systems were evaluated using dissolution rate, phasesolubility, Fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry(DSC) and scanning electron microscope (SEM) studies. The FTIR spectroscopic studiesshowed the stability of STP and absence of STP-PEG-6000 interaction. The DSC and SEMstudies indicated the amorphous state of STP in its binary systems with PEG-6000.Dissolution profile of STP was significantly improved via complexation with PEG-6000 ascompared with the pure drug. The binary system which was prepared using melting methodshowed the highest dissolution rate. The promising results of the prepared binary systems openthe avenue for further oral formulation of STP.