Formulation of Tablet of Nifedipine Co-Crystal for Enhancement of Solubility and Other Physical Properties

ABSTRACT: Nifedipine is commonly prescribed for preterm labor, hypertension, and angina pectoris. According to the Biopharmaceutics Classification System (BCS), nifedipine is categorized as a Class II drug due to its low solubility and high permeability. This study aimed to enhance nifedipine's solubility using a co-crystal approach. Co-crystals are multi-component systems composed of a stoichiometric ratio of an active pharmaceutical ingredient (API) and an approved co-former. Through solvent-assisted grinding, nifedipine co-crystals were successfully prepared with glutaric acid, succinic acid, cinnamic acid, and fumaric acid in a 1:1 stoichiometric ratio. The physicochemical properties of the co-crystals, including infrared spectroscopy, melting point, X-ray diffraction, differential scanning calorimetry, and solubility profiles, were compared to those of pure nifedipine. Among the four co-crystals, the nifedipine-fumaric acid (NFD-FA) co-crystal exhibited a remarkable 90-fold improvement in solubility over pure nifedipine. Consequently, the NFD-FA co-crystal was further characterized. Excipient compatibility studies were conducted, and tablets were formulated using the wet granulation method. In-vitro drug release studies revealed that NFD-FA co-crystal tablets achieved a 45% cumulative drug release within 60 minutes, significantly outperforming the marketed formulation, which released only 27% of the drug in the same period. The observed improvement in solubility is likely due to the formation of hydrogen bonds between nifedipine and the fumaric acid co-former, demonstrating the effectiveness of co-crystallization as a strategy for enhancing drug solubility and dissolution.