Cocystallization has become increasingly important in the drug development because it is a powerful technique to modify key solid-state properties of active pharmaceutical ingredients (APIs), indeed pharmaceutical cocrystals can improve drug solubility and dissolution rates and increase the stability of drugs without compromising their structural integrity. The modification of chemical and physical properties of 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. 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.1 The modulation of solvent/antisolvent composition involves controlling mass transfer in vapor phase through the porous membrane structure, by acting on the operative process parameters.2 Therefore, in this work the antisolvent membrane crystallization process has been used for the direct formulation of carbamazepine- saccharin (CBZ-SAC) cocrystals from water/ethanol solvent mixtures. Since the low solubility of the antiepileptic CBZ in water, CBZ cocrystallization with different conformers provides an excellent strategy to improve its bioavability. By this approach, the experiments were performed at different initial molar ratio API/conformer and at different initial weight ratio of the alcoholic/aqueous solutions. Furthermore, different process parameters affecting on the transmembrane flux such as temperature, membrane area, recirculating rate of the solutions were modified. The results demonstrated the possibility to affect on the co-crystallization process by simply choosing the starting conditions. 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 the solvent flux through the membrane;3 this highlight the possibility to achieve tailor-made cocrystals in a controlled manner by using the opportune membrane crystallization conditions. (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, et al. Cryst. Growth Des. 2010, 10, 449.
Carbamazepine-saccharin cocrystals formulation from solvent mixtures by means of membrane crystallization technique
Di Profio G;
2011
Abstract
Cocystallization has become increasingly important in the drug development because it is a powerful technique to modify key solid-state properties of active pharmaceutical ingredients (APIs), indeed pharmaceutical cocrystals can improve drug solubility and dissolution rates and increase the stability of drugs without compromising their structural integrity. The modification of chemical and physical properties of 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. 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.1 The modulation of solvent/antisolvent composition involves controlling mass transfer in vapor phase through the porous membrane structure, by acting on the operative process parameters.2 Therefore, in this work the antisolvent membrane crystallization process has been used for the direct formulation of carbamazepine- saccharin (CBZ-SAC) cocrystals from water/ethanol solvent mixtures. Since the low solubility of the antiepileptic CBZ in water, CBZ cocrystallization with different conformers provides an excellent strategy to improve its bioavability. By this approach, the experiments were performed at different initial molar ratio API/conformer and at different initial weight ratio of the alcoholic/aqueous solutions. Furthermore, different process parameters affecting on the transmembrane flux such as temperature, membrane area, recirculating rate of the solutions were modified. The results demonstrated the possibility to affect on the co-crystallization process by simply choosing the starting conditions. 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 the solvent flux through the membrane;3 this highlight the possibility to achieve tailor-made cocrystals in a controlled manner by using the opportune membrane crystallization conditions. (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, et al. Cryst. Growth Des. 2010, 10, 449.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
