Solubility Enhancement of Ezetimibe by a Cocrystal Engineering Technique

Abstract

The present study illustrates the formation and characterization of three different cocrystals of ezetimibe using methyl paraben as a coformer, employing three different processes, namely, solution crystallization, liquid assisted grinding, and reaction crystallization. Thermal analysis by differential scanning calorimetry (DSC) and thermogravimetric analysis were used as a primary analytical tool, followed by spectroscopic and crystallographic study as a confirmatory analytical tool. Equilibrium aqueous solubility studies were performed for all cocrystals taking ezetimibe as the control. The ideal solubility of drug and cocrystals was also calculated using data obtained from DSC (heat of fusion, ΔH, and transition melting temperature, T m ). The equilibrium aqueous solubility of ezetimibe was enhanced by about 2-fold in the case of cocrystal prepared by solution crystallization. Cocrystals prepared via reaction crystallization showed solubility that was almost the same as that of pure ezetimibe. The dissolution profile of all cocrystals, with pure ezetimibe as a control, was studied for 2 h in defined biorelevant media. Cocrystal II, prepared by a liquid assisted grinding method, showed significant improvement in solubility at 45 and 120 min, indicating a good dissolution profile. The study demonstrates that pharmaceutical cocrystallization of ezetimibe with methyl paraben can be a possible and potential alternative and effective approach for improving its solubility.

Solubility Enhancement of Lornoxicam by Crystal Engineering

“…There was no correlation between melting point of cocrystal and API/coformer. The transformed melting points of cocrystals may be assigned to the physical non-covalent interaction between drug and coformer, altered packing arrangement or change in the crystallinity of molecules [31] .…”

Physicochemical and dissolution properties of ezetimibe–aspirin binary system in development of fixed-dose combinations

“…The experimentally determined temperatures and enthalpies of phase transitions observed on DSC curves are shown in Table 2. EZT and ASA show a characteristic single endotherm peak (ΔH = 106.7 J g −1 and ΔH = 176.5 J g −1 , respectively) [32] and aspirin (ΔH = 167.6 J g −1 , 141.0 °C) [33]. The DSC curves of the ASA-EZT mixtures clearly indicated that ASA and EZT formed a binary simple eutectic system.…”

Pharmaceutical Cocrystals: An Overview

“…The solid precipitates are also collected and analysed by HPLC to determine the stoichiometry of the complex. If the solid appeared to be a cocrystal based on the HPLC results, it is further characterized by DSC, TGA, and PXRD [84,100,101] .…”