Recrystallizing Primidone through Supercritical Antisolvent Precipitation

Abstract

In this study, an active pharmaceutical ingredient, primidone, was recrystallized through supercritical antisolvent precipitation (SAS) by using CO2 as the antisolvent. The operating parameters of SAS, such as the solvent system, operating temperature and pressure, solution concentration and flow rate, CO2 flow rate, and nozzle diameter, were studied systematically. The solid-state properties of the original and processed primidone, including crystal habit, mean particle size, polymorphic form, and residual solvent content, were analyzed and are discussed. Two novel polymorphic forms of primidone, forms C and D, were obtained, and their crystal habits and mean particle sizes before and after SAS differed significantly. In addition, the dissolution profiles of the original and processed primidone were studied and compared. The experimental results showed that the recrystallized primidone had an enhanced dissolution rate compared with the original primidone. These results demonstrate that through SAS the so...