Investigations on the melting behaviour of triglyceride nanoparticles

Suspensions of triglyceride nanoparticles have been proposed as carrier sys tems for intravenous administration of poorly water soluble drugs. Such nan osuspensions can easily be produced by homogenization of the melted triglyc eride in an aqueous phase. Using special emulsifier blends it is possible t o obtain suspensions with an average size of the recrystallized particles b elow 100 nm (photon correlation spectroscopy z-average). As can be observed by transmission electron microscopy the particles are very thin platelets with thicknesses in the range of only a few molecular layers. Nanoparticles of saturated monoacid triglycerides (smaller than 200 nm) exhibit uncommon melting behaviour, which is expressed in their differential scanning calor imetry curve by multiple endothermal peaks over a temperature range of abou t 10 degreesC. This effect was attributed earlier to the particle thickness distribution in the suspension rather than to polymorphic transitions sinc e all the material exists in the stable P modification. Here we present exp erimental investigations on the correlation between the melting behaviour o f trilaurin nanosuspensions and the particle thickness distribution determi ned by analysis of difference X-ray diffraction patterns recorded at progre ssively higher temperatures in the melting range of the particles. Because of the weak X-ray scattering of the systems investigated synchrotron radiat ion was used besides conventional sources. The Fourier analysis of the diff erence diffraction patterns is described in detail and the advantages and d ifficulties in using this method are discussed. It was observed that the mo lting temperatures of the nanoparticles increase with increasing particle t hicknesses. Simultaneously a decrease in the interplanar (001) spacing with increasing particle thickness was found.