New Sodium Mefenamate – Nicotinamide Multicomponent Crystal Development to Modulate Solubility and Dissolution: Preparation, Structural, and Performance Study

A cocrystal of mefenamic acid (MA) - nicotinamide (NA) has been reported to increase the solubility of MA, but it still does not exceed the solubility of sodium mefenamate (SM). Accordingly, this research dealt with a new salt cocrystal arrangement of SM – NA. Cocrystal screening was performed, foll...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 2021-09, Vol.110 (9), p.3246-3260
Main Authors: Nugrahani, Ilma, Fisandra, Felicia, Horikawa, Ayano, Uekusa, Hidehiro
Format: Article
Language:English
Subjects:
Hydrate
Intrinsic dissolution
Multicomponent crystal
Nicotinamide
Salt cocrystal
Sodium mefenamate
Solubility
Stability
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Summary:A cocrystal of mefenamic acid (MA) - nicotinamide (NA) has been reported to increase the solubility of MA, but it still does not exceed the solubility of sodium mefenamate (SM). Accordingly, this research dealt with a new salt cocrystal arrangement of SM – NA. Cocrystal screening was performed, followed by powder and single-crystal preparation. Solvent drop grinding and slow evaporation at cold and ambient temperatures were employed to produce the multicomponent crystal. Two new salt cocrystals were found as hemihydrates and monohydrates, named SMN-HH and SMN-MH, respectively. SMN-MH single crystals were successfully isolated and structurally analyzed using a single crystal X-ray diffractometer. Pharmaceutical properties were investigated, including hydrate stability, solubility, and intrinsic dissolution. The experiments showed that the hemihydrate was stable under ambient humidity and temperature, and that the monohydrate rapidly changed to hemihydrate. Both hydrates improved the solubility and intrinsic dissolution of SM, but SMN-HH was superior. The data showed that SMN salt cocrystals combine the advantages of salt and cocrystals and show potential for dosage form development.
ISSN:0022-3549
1520-6017
DOI:10.1016/j.xphs.2021.05.022