Enhancement of the solubility of asenapine maleate through the preparation of co-crystals

Abstract

Background: Asenapine maleate, an anti-schizophrenic drug, is a class II drug with low solubility and high permeability. This exerts rate-limiting effect on drug bioavailability. Objective: Improve the solubility/dissolution rate of asenapine maleate and hence the bioavailability using cocrystal approach. Method: Co-crystals were prepared using the solvent evaporation technique. Since the drug has H-bond acceptor count of 6, and H-bond donor count of 2, several co-formers were investigated. The co-crystals were evaluated using PXRD, FTIR spectroscopy, and DSC. Additionally, in-vitro dissolution studies were conducted. Results: The preparation of the co-crystals was successful. The PXRD patterns showed that the resultant mixture was crystalline, the FTIR confirmed the formation of H-bond between the drug and the co-formers and the DSC showed that the mixture exhibited a lower melting point as compared to the components and it was followed immediately by an exothermic peak, which confirmed the formation of co-crystals. The dissolution of all the prepared co-crystals using different co-formers in different ratios was much enhanced as compared to the unprocessed drug. The dissolution of the drug in the drug-nicotinamide co-crystals was much faster than that from the other co-crystals during the first 15-20 minutes. The dissolution of the drug from the physical mixture was slower than from the co-crystals during the first 15-20 minutes but the cumulative amount released after 120 minutes was almost the same. Conclusion: Co-crystals were prepared successfully by improving the solubility/dissolution rate of asenapine maleate, and were expected to enhance the bioavailability of the drug.