Recrystallisation and micronisation of mefenamic acid using high-pressure carbon dioxide

Many drugs exhibit limited absorption, and hence poor bioavailability, in the gastrointestinal tract due to their poor water solubility. Recrystallisation and micronisation are the common approaches for improving the rate of dissolution of these drugs. In this study mefenamic acid, an anti-inflammatory agent which is poorly water soluble, was recrystallised from an organic solution by a variation of the gas antisolvent (GAS) process known as the Aerosol Solvent Extraction System (ASES). An organic solution containing the drug was atomised continuously through a nozzle into compressed carbon dioxide. The effects of parameters such as temperature, pressure, flow rate and organic solvents on the characteristics of the precipitated product were investigated. At the conditions studied, mefenamic acid precipitated in crystalline form. Thin needles of 10 microns in length, and plates of up 200 mum in length and <30 mum in thickness were produced. Changes in operating variables did not alter the polymorphic form of the drug.