Amorphous solid dispersions of cyclosporine A with improved bioavailability prepared via hot melt extrusion: Formulation, physicochemical characterization, and in vivo evaluation

In this study, the amorphous solid dispersions of cyclosporine A (CsA-ASDs) were prepared by hot melt extrusion (HME) with PVP K12 as carrier to improve the oral bioavailability of CsA. The polymers were screened by solubilization and recrystallization inhibition experiments, then the CsA-ASDs were prepared with optimized technological parameters and characterized on thermodynamics and morphology. The results showed that CsA was dispersed among PVP K12 as amorphous form in CsA-ASDs, and the infrared spectrum testified that there was possible hydrogen bond interaction between CsA and PVP K12. The in vivo pharmacokinetics of CsA formulations in rats were analyzed via LC-MS. The AUC of CsA-ASD tablets increased by 7.3 times compared to CsA bulk powder and 3.1 times in contrast to CsA-PM tablets, respectively. The experiment proved that CsA-ASD tablets significantly improved the dissolution and absorption of the drug. This study had a reference value for the bioavailability improvement of oral CsA preparations.

Automated summary

Amorphous solid dispersions of cyclosporine A (CsA-ASDs) were prepared using PVP K12 as a carrier via hot melt extrusion (HME) to improve CsA's oral bioavailability. The experiment indicated a potential hydrogen bond interaction between CsA and PVP K12. In vivo pharmacokinetics showed that CsA-ASD tablets significantly enhanced the drug's dissolution and absorption.