Solid Lipid Nanoparticles as Indomethacin Carriers for Topical Use ( 2 ) : DSC Analysis , Drug Release and Rheological Properties = الجسيمات الدهنية الصلبة النانوية كناقلات الإندوميثاسين للاستخدام الموضعي : المسح التفاضلي الحراري ، انطلاق الدواء و الخواص الريولوجية

Abstract

Solid lipid nanoparticles (SLNs) and nano structured lipid carriers (NLCs) containing or not containing indomethacin (IND) were prepared with either Cetyl palmitate, GeleolTM, or Compritol® 888 ATO as a lipid phase by the hot homogenization technique. In all systems the surfactant was sucrose fatty acid ester SP 30 (HLB 6.0). Differential scanning calorimetry (DSC) experiments were carried out on the freeze - dried samples for all developed plain and drug- loaded formulations after one month of storage at room temperature. The recorded DSC parameters of the samples were compared with those of pure components and physical mixtures of IND with the surfactant or lipids at equivalent ratios to that in nanoparticualtes. Furthermore, rheological analyses of the empty and loaded systems, release experiments at pH 5.0 and the release kinetics were all 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. DSC results showed crystalline particles at room temperature exhibited a shift of the melting endotherm of the lipid phase, with the maximum at a temperature value higher than that of the empty or loaded SLNs except in GeleolTM - based systems. For the investigated formulations a percentage of crystallinity between 61.0 % and 88.33 % was found. Furthermore, IND suffered a marked reduction in its crystallinity and had better solubility in both GeleolTM and Compritol® 888 ATO as compared to Cetyl palmitate screened. Hydrogen bonding with glyceride containing lipids can be one reason for the observed loss of IND crystallinity. All formulations were of creamy texture and viscous especially GeleolTM - based systems. Rheological analysis confirmed that all systems show a complete dependence of the viscosity from the shear stress. The release profiles of different formulations at pH 5.0 allow affirming that these systems are suitable for modified topical delivery. Release studies showed that IND exhibited a prolonged slow release over 24 hours (hrs) with release kinetics in general following zero order model and there was insignificant difference in the amount of released drug depending upon the composition of the formulations.