Fabrication of PLGA in situ forming implants and study on their correlation of in vitro release profiles with in vivo performances

Abstract

In this study, a novel PLGA in situ forming implants (ISFIs) were fabricated and methods for testing the in vitro release profiles were also developed. The correlations between in vitro release profiles and in vivo performances (in vitro–in vivo correlation, IVIVC) were also studied. PLGA with different molecular weights were selected as the polymeric matrix. Biocompatible N-methy1-2-pyrrolidone (NMP) or glyceryl triacetate (GTA) were used as the solvents with the ratios of NMP/GTA from 60/40 (vol/vol) to 20/80 (vol/vol). Eprinomectin (EPR) was chosen as the model therapeutic. In vitro release profiles of the EPR-loaded PLGA ISFIs were investigated using various methods (i.e. ‘tubule’ sample-and-separate and dialysis method). Sprague–Dawley rats were used to study the in vivo pharmacokinetics of EPR-loaded PLGA ISFIs. The release data obtained via ‘tubule’ sample-separate method had a good IVIVC (Level A, R 2 > 0.99). These results showed that the ‘tubule’ sample-separate method was capable of discriminating the EPR-loaded ISFIs which were equivalent in formulation composition with manufacturing differences. Meanwhile, this method could be used to predict the in vivo performances of ISFIs in the investigated animal model.