Comparison of the In Vitro Drug Release Methods for the Selection of Test Conditions to Characterize Solid Lipid Microparticles

Abstract

The release profiles of active substances from microspheres are one of the most important features in solid lipid microparticles (SLM) characterization. Unfortunately, the results of the dissolution tests are largely dependent on the chosen method and test conditions, which in relation to novel dosage forms, such as dispersions of lipid microspheres, are not clearly defined in international compendiums and guidelines. This makes it impossible to compare the results of different studies. The aim of the research was to identify the factors most influencing the variability of the obtained results. An attempt was also made to select the most appropriate method for testing drug substance release from SLM. Various dissolution methods were employed (method I: without a membrane, method II: in a dialysis bag, and method III: in a Side-Bi-Side chamber), and the obtained release profiles of cyclosporine and indomethacin from SLM dispersions were compared. In addition to the effect of membranes, the types of acceptor fluids were also investigated. Significant differences were observed when testing the SLM formulations under various test conditions. The results were significantly influenced by the selected membrane, the acceptor fluid, or the difference in the concentrations of active substance between the donor and acceptor compartments. The burst effect observed in some experimental methods was not noticed in other conditions. At this stage, the method with a dialysis bag has been selected as the most suitable, while the methods without the membrane can only play a complementary role.