Effect of molecular weight and storage times on tolmetin release from poly-D,L-lactide microspheres to lipid model membrane. A calorimetric study

The release of a nonsteroidal antiinflammatory agent (NSAID), 1-methyl-5-p-toluoylpyrrole-2-acetic acid (Tolmetin), from different molecular weight (9000, 16000 or 109000) poly-D,L-lactide (PDLLA) microspheres was tested at two different storage times (one and 6 months), by measuring the drug transfer from loaded microspheres to void model membranes at temperatures above and below polymer glass transition temperature (T-g). Dimyristoylphosphatidylcholine (DMPC) liposomes were selected as the model membrane. At first the effects of drug, in terms of transitional temperature shift (Delta T-m), and enthalpy changes (Delta H) on thermotropic behaviour of liposomes were analysed by differential scanning calorimetry (DSC) to determine the release rate of drug [1]. Calorimetric measurements were performed on suspensions of blank liposomes added to weighed amounts of void and tolmetin loaded microspheres. The samples have been previously incubated at temperatures above and below polymer glass transition temperature. The amount of drug released from the different microparticulate systems to void liposomes was quantified by comparing the T-m shift of the lipid bilayer caused by the drug released from polymeric system, to that caused by free drug. Results show how the release processes are affected by molecular weight and storage times of tolmetin loaded PDLLA microspheres as well as by temperature. The release measured by considering the effect on void liposomes and employing DSC technique results to be an in vitro method. This can be applied to detect therapeutic systems stability by studying the slow kinetics directly at the site of drug uptake.