Comparative study of 'in vitro' release of anti-inflammatory drugs from polylactide-co-glycolide microspheres

A differential scanning calorimetry study has been carried out on the effec t exerted by three anti-inflammatory drugs, Biphenylacetic Acid, Naproxen, and Ketoprofen, released from polylactide-co-glycolide (50:50 w:w) microsph eres (loaded with two different quantities of drug) on the thermotropic beh aviour of dimyristoylphosphatidylcholine liposomes. The aim of this work wa s to study the release rate of a NSAID agent from polylactide-co-glycolide microspheres, by evaluation of the drug effect on the thermotropic behaviou r of dimyristoilphosphatidylcholine unilamellar vesicles, as a model membra ne representing the targeting surface where the drug should be delivered. P olylactide-co-glycolide microspheres loaded with NSAID drugs were prepared by the spray drying method. The lipid samples were unilamellar vesicles cha rged with increasing amounts of free drugs or added to weighed amounts of d rug-loaded microspheres. Free drugs were found to interact with the phospho lipidic bilayer modifying its thermotropic behaviour. In fact, increasing a mounts of drugs in DMPC vesicles shift the peak temperature, assigned to th e gel to liquid-crystal phase transition of purl phosphatidylcholine, towar d lower values. The amount of drug released from the microparticulate drug delivery system versus time was quantified by comparing the T-m shift cause d by the drug released from the polymeric system with that caused by known increasing amounts of the free drugs. The calorimetric technique detects ch anges occurring directly on the adsorption sites, constituted by DMPC vesic les. The release kinetics of these drugs have been reported and compared wi th the 'classical' in vitro release studies executed by a dissolution test. Good agreement was found between the two experimental methods, By calculat ing the drug partition between aqueous phase and lipidic phase, it should b e possible to evaluate the amount of drug present at the surface of the lip idic membrane and the uptake kinetics. The data were explained in terms of physico-chemical characterisation by differential scanning calorimetry and scanning electron microscopy. (C) 1998 Elsevier Science B.V, All rights res erved.