Development and application of a novel tracer system for the evaluation of temperature exposure of lipid nanoparticles in spray drying and dual centrifugation.

Abstract

In recent years, the development of nanocarriers and nanoscale drug delivery systems has become increasingly important, with temperature-intensive processes being an essential part of their preparation and following process steps. This study introduced a novel nanoparticular tracer system to track the highest temperatures to which the particles are exposed to during processing by exploiting the monotropic polymorphism of triglycerides. These nanoparticulate systems enabled an estimation of the temperature exposure of formulations in processes that are otherwise inaccessible or very difficult to access. Two tracer systems were developed using the solid lipids tristearin and tripalmitin, with distinct melting temperatures, and applied for the high-energy processes of spray drying and dual centrifugation. In addition, the experiments provided insights into the effect of stabilizers on triglyceride modifications. It was shown that during spray drying, the highest temperature exposure of the nanoparticles during the process was 4.1 °C and 6.6 °C for tristearin and tripalmitin, respectively, above the outlet air temperature of the spray dryer. In addition, the tristearin tracer system was used to investigate the temperature exposure during dual centrifugation, which indicated that with increasing process time of up to 480 min, all particles were progressively exposed to temperatures above their melting temperature.