Development of supercritical fluid processes for particle coating/encapsulation with polymers.

摘要

This work presents the investigation of particle coating using supercritical fluid processes as novel coating approaches to coat particles from 20 nanometers to 500 microns with different polymers. Particle coating using different supercritical technologies of a modified rapid expansion of a supercritical solution (RESS) for particle coating and a supercritical antisolvent (SAS) process was described.; In the modified RESS process for particle coating, experiments were performed using a pilot-scale supercritical apparatus, glass beads as host particles and two different polymers as coating materials. By adjusting temperature and pressure, the polymer nucleated and precipitated onto the surface of the host particles in a precipitation chamber due to the significantly lowered solubility of polymer in supercritical CO2. The glass beads were found coated with poly vinyl chloride-co-vinyl acetate (PVCVA) and hydroxypropyl cellulose (HPC) although the coating was not uniform and not continuously distributed over the surface of the particles.; The main part of this work is the study of the SAS process for particle coating. The supercritical fluid worked as an antisolvent in the SAS process instead of a solvent in the RESS. The SAS process is based on the principle of SC CO2 induced phase separation in which the solute precipitates due to a high super-saturation produced by the mutual diffusion between organic solvent and SC CO2 when an organic liquid solution comes into contact with SC CO2. Systematic study of the effects of process conditions on the coating of particles in the SAS process was performed. The polymer weight fraction and polymer concentration played critical roles in the agglomeration of coated particles and the thickness of coating. Higher pressure facilitated the Tg depression, enhancing the agglomeration of coated particles. Operating temperature had no visible effect on the coating effect when the temperature was below Tg. The coating quality also was independent of spraying velocity. Surfactants had adverse effects on the coating quality.; The application of SAS particle coating process in the design of drug delivery system was studied. A biopolymer of poly lactide-co-glycolide (PLGA 50/50) and hydrocortisone were selected as the coating material and the model drug, respectively. The hydrocortisone particles were successfully coated with PLGA. At higher polymer loading ratios, the coated drug particles showed sustained release behavior. Higher polymer loading ratio produced higher encapsulation efficiency.