Formulation and Evaluation of Cocrystals of a BCS Class Ii Drug Using Glycine as Coformer

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.

Advances in Cocrystals of Anticancer Agents: Formulation Strategies and Therapeutic Implications

“…DDCs offer potential as a solidstate platform for dual drug delivery, altering the physicochemical properties of constituent medications. Compared to other combination approaches, DDC technology can enhance API characteristics such as bioavailability, stability, and lifecycle management while potentially improving dissolution rates[50].In a study by Carmen[51], a cocrystal of celecoxib (CTC) and tramadol hydrochloride was examined. Dissolution trials revealed a slower release of tramadol hydrochloride and an increased intrinsic dissolution rate (IDR) of celecoxib in the cocrystal.…”