Investigations on the melting behaviour of triglyceride nanoparticles

Abstract

Suspensions of triglyceride nanoparticles have been proposed as carrier systems for intravenous administration of poorly water soluble drugs. Such nanosuspensions can easily be produced by homogenization of the melted triglyceride in an aqueous phase. Using special emulsifier blends it is possible to obtain suspensions with an average size of the recrystallized particles below 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 calorimetry curve by multiple endothermal peaks over a temperature range of about 10 °C. This effect was attributed earlier to the particle thickness distribution in the suspension rather than to polymorphic transitions since all the material exists in the stable β modification. Here we present experimental investigations on the correlation between the melting behaviour of trilaurin nanosuspensions and the particle thickness distribution determined by analysis of difference X-ray diffraction patterns recorded at progressively higher temperatures in the melting range of the particles. Because of the weak X-ray scattering of the systems investigated synchrotron radiation was used besides conventional sources. The Fourier analysis of the difference diffraction patterns is described in detail and the advantages and difficulties in using this method are discussed. It was observed that the melting temperatures of the nanoparticles increase with increasing particle thicknesses. Simultaneously a decrease in the interplanar (001) spacing with increasing particle thickness was found.