Development of a dissolution method based on lipase for preclinical level A IVIVC of oral poly(ε-caprolactone) microspheres

Abstract

Level A in vitro/in vivo correlation (IVIVC) of poly (ε-caprolactone) (PCL) microspheres for oral administration is challenging since in vitro PCL dissolution takes longer. The aims of this study were: 1) to develop three compositionally equivalent formulations of PCL microspheres with a different release rate of 6-methylcoumarin (6 MC), a drug candidate class IIc according to biopharmaceutical classification systems. 2) To develop a dissolution test for 6 MC-loaded PCL microspheres for oral administration. 3) To evaluate the influence of the PCL microspheres on the pharmacokinetic parameters of 6 MC and 4) to investigate a possible level A IVIVC of the 6 MC-loaded PCL microspheres. 6 MC-loaded PCL microspheres with different release rate were prepared and its physicochemical properties were evaluated as well as its release profiles. The pharmacokinetic parameters of the microspheres were investigated in Wistar rats. As results, it was possible to develop three compositionally equivalent 6 MC-loaded PCL microspheres with different release rate. Microspheres significantly affect pharmacokinetic parameters of 6 MC and a level A IVIVC was achieved for 6 MC-loaded PCL microspheres by using a dissolution method that includes lipase in the release medium. Developed dissolution method was able to predict the in vivo performance of 6 MC-loaded PCL microspheres in the investigated animal model.