CALORIMETRIC STUDIES ON TOLMETIN RELEASE FROM POLY-DL-LACTIDE MICROSPHERES TO LIPID MODEL MEMBRANE

The aim of this work was to study the rate of release of an NSAI agent from poly-DL-lactide (PDLLA) microspheres, by evaluating the effect o f the drug on the thermotropic behaviour of dimyristoylphosphatidylcho line liposomes (DMPC), selected as a model membrane. Polylactide micro spheres loaded with 1-methyl-5-p-toluoylpyrrole-2-acetic acid (tolmeti n) were prepared by the spray-drying method. Samples made of liposomes charged with free drug and suspensions of blank liposomes added to we ighed amounts of tolmetin-loaded microspheres were analyzed by DSC. Ca lorimetric analyses were performed on samples previously incubated at temperatures below and above the polymer glass transition temperature (T-g). Free drug was found to interact with the phospholipidic bilayer by modifying its thermotropic behavior. The amount of drug released f rom the microparticulate to void liposomes was quantified by comparing the T-m shift caused by drug release from the polymeric system with t hat due to free drug. The results demonstrate the extent to which the release process is affected by temperature throughout the polymeric st ructure. In conclusion, the calorimetric technique detects changes occ urring directly on the adsorption sites and can thus be applied to stu dy slow kinetics directly al the site of drug uptake.