Electrospray technology as a probe for cocrystal synthesis: Influence of solvent and coformer structure

Abstract

In the present work electrospray technology has been used for cocrystal synthesis of structurally diverse drug molecules. Additionally, influence of solvent and coformer structure on generation of pharmaceutical cocrystals was also investigated. Carbamazepine (CBZ) and itraconazole (ITZ), structurally diverse molecules with vast difference in physicochemical properties were taken as a model drugs. Nicotinamide (NIC) was used as a coformer for cocrystallization of CBZ. Solutions (methanol and ethanol) of CBZ/NIC (1:1 ratio) were electrosprayed to analyze influence of solvent properties on cocrystal formation. Additionally, cocrystallization of ITZ was attempted using structurally diverse coformers [fumaric acid (FA) and succinic acid (SA)] in 2:1 ratio of drug to coformer. CBZ cocrystals recovered from methanol and ethanol were abbreviated as MCNC and ECNC whereas ITZFA and ITZSA were the abbreviations for cocrystals of ITZ. MCNC and ECNC were recovered in pure form indicating that the solvents screened had no influence on cocrystallization of CBZ. Similarly, ITZSA and ITZFA were recovered in pure form even though the ratio of API to coformer was 2:1 suggesting specificity of the electrospray technology. Thus electrospray technology, a single step, selective method for continuous manufacturing of cocrystals can serve as an alternative to traditional methods of cocrystal synthesis.