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 AUC_0–t and C_max 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.

• Amorphous
• fumed silica
• oral bioavailability
• spironolactone
• supercritical carbon dioxide

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.