Calorimetric studies on tolmetin release from poly- dl-lactide microspheres to lipid model membrane

Abstract

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 of the drug on the thermotropic behaviour of dimyristoylphosphatidylcholine liposomes (DMPC), selected as a model membrane. Polylactide microspheres loaded with 1-methyl-5- p-toluoylpyrrole-2-acetic acid (tolmetin) were prepared by the spray-drying method. Samples made of liposomes charged with free drug and suspensions of blank liposomes added to weighed amounts of tolmetin-loaded microspheres were analyzed by DSC. Calorimetric 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 from the microparticulate to void liposomes was quantified by comparing the T m shift caused by drug release from the polymeric system with that due to free drug. The results demonstrate the extent to which the release process is affected by temperature throughout the polymeric structure. In conclusion, the calorimetric technique detects changes occurring directly on the adsorption sites and can thus be applied to study slow kinetics directly at the site of drug uptake.