Drug-Drug Coamorphous Systems: Characterization and Physicochemical Properties of Coamorphous Atorvastatin with Carvedilol and Glibenclamide
چکیده
In this study, coamorphous form of atorvastatin calcium (ATC) with two drugs, i.e., carvedilol (CVD) and glibenclamide (GLN) in 1:1 stoichiometry, were prepared from solvent evaporation method and they were characterized and their physicochemical properties determined. The coamorphous forms were characterized using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), and powder X-ray diffraction (PXRD). The kinetic solubility of coamorphous form of ATC with CVD (ATC-CVD) and GLN (ATC-GLN) were determined along with stability of supersaturated state of coamorphous forms using developed accurate and precise UV-net analyte signal standard addition method (chemometrics-based approach) and HPLC. The results of DSC and analysis of glass transition temperatures (T (g)), PXRD, and FT-IR indicated that the crystalline studied drugs were converted to coamorphous forms, with unique thermal behaviors, revealing a molecular interaction between two components. The kinetic solubility data revealed that coamorphous forms have better metastable solubility than those of crystalline state. In addition, these systems showed greater solution stability than those for amorphous form of single components reported in the literature. Coamorphous ATC-CVD and ATC-GLN were shown to have improved physicochemical and solution stability properties as compared to crystalline components.