DESIGN AND CHARACTERIZATION OF GLIBENCLAMIDE-CAFFEIC ACID COCRYSTALS VIA CRYSTAL ENGINEERING

JYOTI MALIK; HIMANSHU SACHDEVA; ANURAG KHATKAR; ARUN NANDA

doi:10.22159/ijap.2025v17i1.51992

Authors

JYOTI MALIK Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak (Haryana), India. School of Pharmaceutical Sciences, Apeejay Stya University, Sohna Gurugram, (Haryana), India https://orcid.org/0000-0003-0348-6133
HIMANSHU SACHDEVA Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak (Haryana), India https://orcid.org/0009-0003-9341-0200
ANURAG KHATKAR Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak (Haryana), India
ARUN NANDA Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak (Haryana), India

DOI:

https://doi.org/10.22159/ijap.2025v17i1.51992

Keywords:

Cocrystals, Glibenclamide, Caffeic acid, Solubility, Co-former, Solvent evaporation method

Abstract

Objective: The present work aims to prepare and characterize glibenclamide cocrystals.

Methods: Glibenclamide was chosen as a model drug due to its low solubility and classification as a Biopharmaceutical Classification System (BCS) class II drug. Among the various methods for selecting appropriate coformers, the pKa and thermal methods were employed. Using these approaches, a formulation with caffeic acid, prepared through the solvent evaporation method, demonstrated the best results as evaluated by parameters such as dissolution rate, X-Ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Hot Stage Microscopy (HSM), Scanning Electron Microscopy (SEM).

Results: In the FTIR spectra, the sulfonamide group of the drug formed hydrogen bonds with the hydroxyl groups of the coformer, suggesting the presence of hydrogen bonding interactions between the components. HSM and DSC revealed that the melting point of the cocrystals occurred at a different temperature for the pure drug and coformer. This significant change in the melting point indicates the formation of a new crystalline phase in the cocrystals, suggesting that the drug and coformer interact at the molecular level to form a unique solid structure. XRD analysis showed diffraction peaks at distinct points with higher intensity in the cocrystals, indicating a new crystalline structure. SEM images of the cocrystals revealed a well-defined crystalline morphology, which differed from the irregular shapes of the pure drug and coformer. The cocrystals demonstrated a significantly improved dissolution rate compared to the pure drug and marketed formulation. In animal studies conducted on male Wistar rats, cocrystals reduced blood glucose levels more rapidly than pure glibenclamide. This enhanced antidiabetic efficacy suggests that the cocrystal formulation not only improves dissolution but also accelerates the therapeutic onset of action.

Conclusion: These findings confirmed that the glibenclamide cocrystals prepared with caffeic acid help effectively improve the drug’s low solubility.

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