Formation of Mefenamic Acid Nanocrystals with Improved Dissolution Characteristics

Abstract

An industrially feasible formulation approach combining media milling and spray-drying was applied to improve dissolution characteristics of the poorly soluble drug mefenamic acid (MA). The approach was studied for two MA polymorphs at different stressing and pH conditions. It was found that final MA product particle sizes are rather determined by the solid-liquid equilibrium than by mechanical fracture. Obtained drug particles are only composed of the most stable polymorph. Direct compressed tablets containing MA nanocrystals exhibit a significant improvement of in vitro dissolution kinetics as compared to tablets with micronized drug particles.