Design and Critical Characterization the Pharmaceutical Cocrystal of Azelnidipine With Coformers for Boosting Physicochemical Properties

Purpose

Azelnidipine, a BCS class II antihypertensive medication, is known for its low solubility and high permeability. In order to enhance its properties, generic GRAS (Generally Recognized as Safe) molecules were utilized in combination with crystal engineering to create novel cocrystal forms of azelnidipine.

Methods

By varying the ratios (1:1, 1:2, and 2:1) and utilizing succinic acid and nicotinic acid as building blocks, pharmaceutical cocrystals of azelnidipine were successfully developed. A solvent ultrasonic technique was employed to synthesize these cocrystals, which were then subjected to various analytical techniques such as X-ray diffraction, differential scanning calorimetry, NMR, MASS, and FT-IR to confirm their purity, synthesize cocrystals, and evaluate their stability over a six-month period. X-ray crystal data revealed the characteristics of hydrogen bonding and interactions between the drug and co-formers, while differential scanning calorimetry highlighted differences in thermal behaviour and cocrystal formation.

Results

Upon testing solubility and dissolution rate, it was observed that all cocrystals exhibited faster dissolution and higher equilibrium solubility compared to the parent medication. Among the cocrystals, those formed with succinic acid were found to be the most soluble form of azelnidipine.

Conclusion

Overall, the development of pharmaceutical cocrystals of azelnidipine has shown promising results in enhancing the drug's solubility and dissolution rate, potentially leading to improved therapeutic outcomes.