PREPARATION, CHARACTERISATION, EVALUATION AND DFT ANALYSIS OF CILNIDIPINE-L-PHENYLALANINE COCRYSTAL

Abstract

Objective: The objective of this study was to prepare, characterise and evaluate pharmaceutical cocrystals of Cilnidipine using L-phenylalanine as the coformer to enhance the aqueous solubility of Cilnidipine. It was also proposed to study the mechanism of cocrystal formation based on Density Functional Theory (DFT) using Gaussian software. Methods: To overcome the limitation of poor aqueous solubility of Cilnidipine, a 1:1 pharmaceutical cocrystal of Cilnidipine was prepared using L-phenylalanine as the coformer by liquid assisted grinding (LAG) technique. The resultant cocrystals were characterised by Fourier transform-infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and field emission scanning electron microscopy (FE-SEM). They were evaluated for their saturation solubility in water. The mechanism of cocrystal formation was studied at the DFT level of theory. Results: The band broadening of the–NH and–NO peaks in FTIR spectra of Cilnidipine indicated the formation of hydrogen bonds in the prepared cocrystals. A single sharp melting endotherm at 218.40 °C in the DSC curve confirmed the formation of cocrystals. The appearance of new peaks in the PXRD pattern of the prepared cocrystals showed the formation of a new crystalline phase. FE-SEM analysis also confirmed the above findings. The prepared cocrystals exhibited 3.31 folds enhancement in saturation solubility. The DFT analysis showed the formation of intrmolecular hydrogen bonding between the–NO of Cilnidipine and–NH of L-phenylalanine. Conclusion: The present study demonstrated a successful approach for enhancing the solubility of poorly water-soluble drug Cilnidipine by cocrystallisation technique using L-phenylalanine as the coformer.