Membrane technology for the final direct formulation of active pharmaceutical ingredients from multicomponent solutions

This work aimed to develop a versatile method for the final formulation, in the solid crystalline state, of active pharmaceutical ingredients (API) from multicomponent solutions. In more detail, membrane crystallization [1], working in antisolvent (demixing) configuration [2], has been used to obtain solid crystalline products from solutions containing carbamazepine - isonicotinamide (CBZ-INA), carbamazepine - nicotinamide (CBZ-NA), carbamazepine - saccharin (CBZ-SAC), or carbamazepine - aspirin (CBZ-ASP) combinations in mixtures of water and ethanol as solvent. Results demonstrated that, depending on the control of the transmembrane flux and the solution composition, the preferential crystallization of a specific API or a cocrystal of the two molecules can be obtained from each combination. In the first case, crystals in a definite polymorphic phase were grown with prevalence higher than 90% over the other forms. This demonstrated that membrane-based crystallization technology can be suitable to achieve polymorphic selection even in the crystallization from multicomponent systems. Furthermore, the technique has been proven to work also in the production of cocrystals, a new formulation for poor-water soluble or low-bioavailable drugs. [1] Di Profio, G.; Curcio, E.; Drioli, E. Supersaturation Control and Heterogeneous Nucleation in Membrane Crystallizers: Facts and Perspectives, Ind. Eng. Chem. Res. 2010, 49, 11878-11889. [2] Di Profio, G.; Stabile, C.; Caridi, A.; Curcio, E.; Drioli, E. Antisolvent membrane crystallization of pharmaceutical compounds. J. Pharm. Sci. 2009, 98, 4902.