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In-vitro and in-vivo study of amorphous spironolactone prepared by adsorption method using supercritical CO2

Abstract Objective: The aim of this study was to improve the oral bioavailability of spironolactone (SP). Method: SP was adsorbed on the fumed silica using supercritical CO2 (scCO2) technology and further compressed into tablets. The morphology was observed by scanning electron microscopy (SEM), and the crystalline form was investigated by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). The dissolution test was performed in water, 0.1 M HCl solution, pH 4.5 acetate buffers and pH 6.8 phosphate buffers using the paddle method. The pharmacokinetics was undertaken in six dogs in a crossover fashion. Results: SP was successfully prepared into tablets and presented in amorphous state. SP-silica scCO2 tablets displayed higher dissolution profiles than SP-silica physical mixtures tablets in different media. The AUC0–t and Cmax of SP-silica supercritical CO2 was 1.61- and 1.52-fold greater than those of SP-silica physical mixtures (p < 0.05), respectively. Conclusion: It is a promising method in improving dissolution and bioavailability by adsorbing SP, a poorly soluble drug, on the fumed silica using rapid expansion of supercritical solutions.