Preparation, Characterization and In Vitro Evaluation of Indomethacin Loaded Solid Lipid Nanoparticles

Solid lipid nanoparticles (SLNs) and nano structured lipid carriers (NLCs) containing or not containing indomethacin (IND) were prepared with either Cetyl palmitate, Geleol™, or Compritol® 888 ATO as a lipid phase. In all systems the surfactant was sucrose fatty acid ester SP 30. The systems were characterized through particle size analyses and zeta potential measurements. The entrapment efficiency of the particles was calculated. 1H-NMR of the nanosuspensions allowed investigating the crystallinity of the particles. Furthermore, release experiments of a model drug (Indomethacin) were performed and the release kinetics was investigated. This study focuses on the investigation of how the nature and the amount of formulation components are able to modify the properties of the system. In particular, the concentration of the surfactant used for the nanosuspension stabilization, the nature and concentration of the lipid phase used for the nanoparticles preparation, as well as the drug- lipid ratio employed in the preparation of loaded SLNs were investigated. From the results obtained, SLNs with a narrow monomodal size distribution range from 190 to 400 nm were produced. The polydispersity results showed a polydispersity index (PdI) in general lower than 0.25. The incorporation of IND in most cases increased the sizes of the SLN particles and the particles aggregation which was represented by significantly higher Z-average (intensity weighted mean of particle sizes) and PdIs. The freshly prepared SLNs have a potential greater than -30 mV which was sufficient for a stable system in combination with the sterically stabilizing effect of the emulsifier. Glyceride SLNs showed good drug encapsulation but with a formation of aggregates. In contrast, wax- based SLNs possessed good physical stability with no aggregation but lacked sufficient drug encapsulation. These differences were attributed in part to different crystal packing. 1H-NMR results showed crystalline particles at room temperature. The comparison among the release profiles of different formulations allows affirming that these systems are suitable for modified oral delivery formulations. Release studies at pH 7.4 showed that IND release exhibited a biphasic pattern with an initial burst and prolonged release over 24 hours with kinetics obeying Higuchi model. Production of IND- loaded SLNs with new solid lipids and its future formulation as tablets could be new, cost effective and commercially viable alternative to the commercial products.