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

Abstract

A differential scanning calorimetry study has been carried out on the effect exerted by three anti-inflammatory drugs, Biphenylacetic Acid, Naproxen, and Ketoprofen, released from polylactide- co-glycolide (50:50 w:w) microspheres (loaded with two different quantities of drug) on the thermotropic behaviour of dimyristoylphosphatidylcholine liposomes. The aim of this work was to study the release rate of a NSAID agent from polylactide- co-glycolide microspheres, by evaluation of the drug effect on the thermotropic behaviour of dimyristoilphosphatidylcholine unilamellar vesicles, as a model membrane representing the targeting surface where the drug should be delivered. Polylactide- co-glycolide microspheres loaded with NSAID drugs were prepared by the spray drying method. The lipid samples were unilamellar vesicles charged with increasing amounts of free drugs or added to weighed amounts of drug-loaded microspheres. Free drugs were found to interact with the phospholipidic bilayer modifying its thermotropic behaviour. In fact, increasing amounts of drugs in DMPC vesicles shift the peak temperature, assigned to the gel to liquid–crystal phase transition of pure phosphatidylcholine, toward lower values. The amount of drug released from the microparticulate drug delivery system versus time was quantified by comparing the T m shift caused by the drug released from the polymeric system with that caused by known increasing amounts of the free drugs. The calorimetric technique detects changes occurring directly on the adsorption sites, constituted by DMPC vesicles. The release kinetics of these drugs have been reported and compared with the `classical' in vitro release studies executed by a dissolution test. Good agreement was found between the two experimental methods. By calculating the drug partition between aqueous phase and lipidic phase, it should be possible to evaluate the amount of drug present at the surface of the lipidic membrane and the uptake kinetics. The data were explained in terms of physico-chemical characterisation by differential scanning calorimetry and scanning electron microscopy.