Suhair S. Al-Nimry* and Mai S. Khanfar
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.
Asenapine maleate, Enhancement of the solubility, co-formers, co-crystals
Department of Pharmaceutical Technology, Jordan University of Science and Technology, P.O. Box 3030, Irbid, 22110, Department of Pharmaceutical Technology, Jordan University of Science and Technology, P.O. Box 3030, Irbid, 22110