Solid lipid nanopaticles as colloidal drug carries for parenteral administration : study on preparation parameters and their physiocochemical characteristics

Abstract

Solid lipid nanoparticles (SLN) for parenteral administration was produced by hot melt homogenization technique. The effects of homogenization parameters were studied and optimized to yield the smallest particle size and to use the least energy. Trimyristin, tripalmitin, tristearin, and stearic acid were used as lipid matrices, and the4ir stabilizers were poloxamer 407, tween 80 and egg lecithin. Four drugs with different solubilities: diltiazem hydrochloride, theophylline, piroxicam, and ibuprofen were loaded into these carriers. The preparations were sterilized and their physicochemical characteristics were investigated. The results showed that 3% poloxamer 407 could stabilize 5% tripalmitin giving the smallest particles in nanometer size range. Its d(v,0.5) was 0.39 µm and 0.40 µm before and after autoclaving, respectively, and maintained in this size range for more than 1 year. Its viscosity was very low. The zeta potential was not sufficiently high to stabilize the dispersion solely by electrostatic repulsive, however, additional steric effect of poloxamer 407 could result in the stable dispersion. Diltiazem hydrochloride, theophylline, and ibuprofen loaded SLN could be prepared into stable preparations, which was not the case of piroxicam. Precipitation of drug occurred and incompatibility of piroxicam and tripalmitin was confirmed from the infrared spectra. Entrapment efficiency of ibuprofen in tripalmitin was higher than that of the other drugs. However, the higher entrapment efficiency of diltiazem hydrochloride could be improved by increasing the pH of the preparation nearly to its pKa, therefore its non-ionized form and lipophilicity were increased. The release profiles of diltiazem hydrochloride and ibuprofen SLN could be sustained for more than 24 hours and 7 days, respectively. Their release kinetics followed Higuchi and power expression models. DSC thermograms and X-ray diffractograms indicated that drug in lipid matrix was not in crystalline form. These carrier systems could be reproduced to have the similar properties in each batch.