Surface treatment: a potential approach for enhancement of solid-state photostability

The potentials of a simple surface treatment technique aiming at modifying solid-state properties with emphasis on photostability were investigated using methyldopa (MD), a photosensitive drug substance. MD was treated with a preselected solvent by stirring a drug suspension in the solvent in a predetermined solid/solvent ratio under controlled conditions. At the end of the solvent treatment period, MD powder was separated, dried and screened. Changes in the solid-state properties of surface-treated MD were monitored using flowability measurements, scanning electron microscopy, thermal analysis and dissolution rate. Further, photostability testing, according to the ICH guidelines, was conducted using compressed disks of MD treated with solvents in the absence and presence of antioxidants, namely ascorbic acid, butylated hydroxytoluene (BHT) and cysteine HCl. The color change (DeltaE) was determined according to the CIELAB system. Surface treatment of MD drug substance with ethanol, methanol and isopropanol resulted in a marked improvement in flowability which was associated with morphological crystalline changes. Treatment of MD with methanol provided free flowing spherical agglomerates. Disks of solvent-treated MD showed improved photostability which was further potentiated by the inclusion of antioxidants, although only traces of the antioxidant were retained in the treated powder. Tablets containing MD surface treated with methanol containing a mixture of 2% ascorbic acid and 0.2% BHT were prepared by direct compression using a simple formula. The tablets conformed to official requirements.