FORMULATION AND EVALUATION OF COCRYSTALS OF A BCS CLASS II DRUG USING GLYCINE AS COFORMER

ARUN NANDA; RACHNA ANAND

doi:10.22159/ijap.2022v14i6.46090

Authors

ARUN NANDA Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, Haryana 124001, India
RACHNA ANAND Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, Haryana 124001, India

DOI:

https://doi.org/10.22159/ijap.2022v14i6.46090

Keywords:

Cocrystals, Solubility, Bioavailability, Ezetimibe, Coformer, Glycine

Abstract

Objective: Development of pharmaceutical co-crystals is an interesting area of research as co-crystals are unique because they have the advantages of maintaining drug’s intrinsic properties along with improvement in its physicochemical attributes. Objective of this research was to improvise solubility of a Biopharmaceutics Classification System (BCS) class II drug (Ezetimibe) along with better dissolution profile using cocrystallization technique.

Methods: In the present study, pharmaceutical cocrystals of a BCS class II drug, Ezetimibe, were prepared using glycine as coformer using neat grinding method. Prepared cocrystals were characterized using Hot Stage Microscopy (HSM), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared (FTIR) and Powder X-Ray Diffract meter (PXRD). In addition, solubility and dissolution studies were also performed.

Results: HSM study and DSC study represented melting at Ezetimibe (166 °C), Glycine (233 °C) and cocrystals (174 °C), respectively. Melting point of cocrystal is between API and coformer, indicating towards interaction. During XRD studies, a new peak was observed at 14.7193 and 23.3211 at position 2θ in comparison to parent peaks of Ezetimibe (18.5537, 19.2737 and 21.6487) and Glycine (19.0631, 21.8418, 25.3521, 35.4189, 39.0489 and 39.1631). PXRD pattern of cocrystals represented several newer peaks (-OH group in API shifted from 3241.42 cm^-1 to 3202.61 cm^-1and-NH₂ in Glycine shifted from 1601.86 cm^-1 to 1690.18 cm^-1). This indicated towards possible interaction between these two-group leading to cocrystal formation. Improvement in dissolution profile of cocrystals (89.59%) was observed over the pure drug (32.41%) in 90 min.

Conclusion: Pharmaceutical cocrystals of Ezetimibe with glycine as coformer represented a promising approach in tailoring the physicochemical properties.

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