A Microfluidic Approach for a Continuous Crystallization of Drug Carrier Nanoparticles

摘要

Solid lipid nanoparticles (SLN) as a new generation of drug carrier systems for pharmaceutical applications are currently under intensive investigation. They can be prepared by melt-homogenization of a matrix lipid in surfactant-containing aqueous media. In the corresponding production sequence, the crystallization of the resulting lipid droplets to solid nanoparticles is a crucial step for reproducible product properties. Hitherto, melt crystallization in these dispersions is usually performed in a batchwise process under poorly defined cooling conditions, without much regard to the well-known aspects of heat transfer, homogeneity in the product mixture, and precise process control. In addition, these setups often only allow the application of low cooling rates. The use of high, well-defined cooling rates would, however, offer very interesting new possibilities for the manufacturing of such drug carrier systems. Due to their small volumes and superior heat and mass transfer performance, microfluidic devices ensure a precise setting and control of the optimum process conditions. In this study, a microfluidic process for the continuous melt crystallization of SLN suspensions is established, allowing for high and well-defined cooling rates. For various cooling rates, the crystallized SLN were analyzed by differential scanning calorimetry, X-ray diffraction, laser diffraction, and photon correlation spectroscopy. The samples were also analyzed after well-defined storage times in order to investigate the stability of the suspensions.