Membrane crystallization technique for the direct formulation of pharmaceutical co-crystals from solvent mixture

In recent years, identification and development of active molecules cocrystals gained increasing interest in the pharmaceutical industry because cocrystallization represents an effective means of enhancing drug's physicochemical properties such as physical stability, melting point, solubility and dissolution rate. The modification of chemical and physical properties of active pharmaceutical ingredients (APIs), can lead to use co-crystals as an alternative solid dosage form and to extend patent life of products. Here, a membrane-based crystallization technique to produce pharmaceutical cocrystals from solvents mixtures is proposed.1 This technique represents a modification of conventional membrane crystallization and operates using a membrane to control the solvent/antisolvent demixing in a drug solution, in order to promote supersaturation and thus induce crystallization. The modulation of solvent/antisolvent composition involves controlling mass transfer in vapor phase trough the porous membrane structure, by acting on the operative process parameters.2 The antisolvent membrane crystallization process is proposed to carry out the cocrystallization of the antiepileptic carbamazepine (CBZ) with different conformers such as nicotinamide, isonicotinamide, saccharin, aspirin, ascorbic acid, from water/ethanol mixtures. The use of the membrane to finely modulate solvent removal in vapor phase, allows to produce crystalline forms with high polymorphic purity, in fact it is possible to better control the influence on the polymorphic composition of the co-crystals opportunely changing different parameters affecting on transmembrane flux;3 this highlight the possibility to achieve tailor-made cocrystals in a controlled manner by choosing the opportune membrane crystallization conditions. For this reasons, further experimental tests with different APIs/conformers combinations are addressed to enlarge the range of application of the proposed technology and to investigate the effect of the process variables involved in the membrane crystallization process on the structural properties of the crystalline material produced. References (1) G. Di Profio, C. Stabile, A. Caridi, E. Curcio, E. Drioli J. Pharm. Sci. 2009, 98, 4902. (2) G. Di Profio, E. Curcio, E. Drioli, Ind. Eng. Chem. Res 2010, 49, 11878. (3) G. Di Profio, A. Caridi, R. Caliandro, A. Guagliardi, E. Curcio, E. Drioli, Cryst. Growth Des. 2010, 10, 449.