CHARACTERISATION, EVALUATION AND DENSITY FUNCTIONAL ANALYSIS OF CILNIDIPINE-NICOTINAMIDE COCRYSTALS DEVELOPED BY LIQUID ASSISTED GRINDING TECHNIQUE: A SUSTAINABLE APPROACH FOR ENHANCED SOLUBILITY

RENJISH CHERUKKOTH; SIBI P. ITTIYAVIRAH; JYOTI HARINDRAN; SUDHAKARAN NAIR C. R.

doi:10.22159/ijap.2024v16i2.49848

Authors

RENJISH CHERUKKOTH College of Pharmaceutical Sciences, Govt. T D Medical College, Alappuzha, Kerala, India https://orcid.org/0000-0002-8162-2527
SIBI P. ITTIYAVIRAH Department of Pharmaceutical Sciences, Centre for Professional and Advanced Studies, RIMSR, Kottayam, Kerala, India
JYOTI HARINDRAN Department of Pharmaceutical Sciences, Cheruvandoor Campus, Centre for Professional and Advanced Studies, Kottayam, Kerala, India
SUDHAKARAN NAIR C. R. College of Pharmaceutical Sciences, Govt Medical College, Thiruvananthapuram, Kerala, India

DOI:

https://doi.org/10.22159/ijap.2024v16i2.49848

Keywords:

Cocrystals, Cocrystals Cilnidipine, Cilnidipine Nicotinamide, Liquid-assisted grinding, Solubility enhancement, Green, Sustainable

Abstract

Objective: Improving the solubility of poorly water-soluble drugs has always been a challenge in drug development. This study aimed to enhance the aqueous solubility of a poorly water-soluble drug, Cilnidipine, by cocrystallisation method using liquid-assisted grinding (LAG) technique with Nicotinamide as the coformer. The study also aimed to understand the mechanism of cocrystal formation by quantum mechanical calculations.

Methods: The Cilnidipine-Nicotinamide cocrystals were prepared in various stoichiometric ratios using the liquid-assisted grinding (LAG) technique. The cocrystals obtained were characterised by vibrational spectroscopy, thermal methods such as differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and surface morphology by field emission scanning electron microscopy (FE-SEM). The cocrystals were evaluated for saturation solubility, and the mechanistic study of cocrystal formation was performed using the Gaussian 09 software package.

Results: FT-IR spectra of the formulated cocrystal indicated the intermolecular hydrogen bond formation between-N-H of Nicotinamide and the nitro group of Cilnidipine. DSC analysis showed a single endotherm at 96.76 °C, PXRD patterns were different from that of the reactants, and FE-SEM analysis revealed the changes in the surface morphology of the obtained cocrystal. The prepared cocrystal showed a 26.36-fold enhancement in the aqueous solubility of Cilnidipine. The DFT study demonstrated the formation of a strong intermolecular hydrogen bonding between the nitro-oxygen atom of Cilnidipine and the amide hydrogen atom of Nicotinamide in cocrystal formed.

Conclusion: This study highlights the potential of the liquid-assisted grinding method for preparing cocrystals as a sustainable and reliable approach to address the challenges posed by poorly water-soluble drugs.

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