Drug Release from Lipid Microparticles-Insights into Drug Incorporation and the Influence of Physiological Factors

The aim of this study was to assess the impact of physiological factors, namely tear fluid and lysozyme enzyme, as well as surfactant polysorbate, on the release profile from solid lipid microparticles (SLM), in the form of dispersion intended for ocular application. Indomethacin (Ind) was used as a model drug substance and a release study was performed by applying the dialysis bag method. Conducting release studies taking into account physiological factors is expected to improve development and screening studies, as well as support the regulatory assessment of this multi-compartment lipid dosage form. The effect of the lysozyme was directly related to its effect on lipid microparticles, as it occurred only in their presence (no effect on the solubility of Ind). Polysorbate also turned out to be an important factor interacting with the SLM surface, which determined the release of Ind from SLM. However, in study models without tear fluid or lysozyme, the release of Ind did not exceed 60% within 96 h. Ultimately, only the simultaneous application of artificial tear fluid, lysozyme, and polysorbate allowed for the release of 100% of Ind through the SLM dispersion. The examination of the residues after the release studies indicated the possibility of releasing 100% of Ind from SLM without complete degradation of the microparticles' matrix. The incubation of SLM with tear fluid confirmed a similar influence of physiological factors contained in tear fluid on the surface structure of SLM as that observed during the in vitro studies.