Diazepam solid lipid nanoparticles using glycerol behenate produced by hot homogenization process

Abstract

The purpose of this present study was to prepare diazepam loaded solid lipid nanoparticles (SLN) and to investigate factors affecting the physicochemical properties for parenteral applications. SLN was prepared by hot homogenization method. This method consisted of two processes; preparing the pre-emulsion using high speed homogenizer and reducing the particle size by high pressure homogenization. The stabilizers used were poloxamer 188, poloxamer 407, Phospholipon (R)80, Epikuron (R)200, tween 20 and tween 80. The results indicated that type and concentration of stabilizers were important factors for producing SLN. The poloxamer 188, poloxamer 407 and tween 20 provided insufficient stabilization after autoclaving. Phospholipon (R)80 and Epikuron (R)200 could not stabilize SLN. The formulation composed of tween 80 could form stable autoclaved SLN conceivably by steric stabilization. The SLN containing 5% glycerol behenate and 4% tween 80 yielded the smallest particle size. The mean particle sizes of such formulation detected by photon correlation spectroscopy before and after autoclaving were 118.4 and 122.0 nm, respectively, which were insignificantly different (p>0.05, t-test). It was found that mean particle sizes of 0.1-0.9% diazepam loaded SLN were larger than those of drug free formulation both before and after autoclaving. Two-way ANOVA test revealed that the content of microparticles was depended upon homogenization pressure. Diazepam loaded SLN with narrow size distribution could be prepared under pressure of 20,000 psi and 5 recycle times. The release profiles of diazepam loaded SLN could be controlled for more than 60 hours. Their release kinetics followed Higuchi model. The IR spectra showed that there was no interaction between diazepam and other components. The DSC thermograms and X-ray diffractograms demonstrated that diazepam in lipid matrix was in either molecularly dispersed or amorphous form.