Thesis (M.Eng.)--Chulalongkorn University, 2009

For the improvement of therapeutic effectiveness, coating of drug particles with polymer has been used widely in pharmacy and medicine for controlled-release applications. The polymer coating could help improve the circulation of drug and maintain the concentration of therapeutic agents in the blood vessels. In this research, coating of microsize and nanosize powders with a polymer has been investigated for the production of controlled-release particulate drug delivery systems, such as microcapsules and nanospheres. Poly(D,L-lactide-co-glycolide) or PLGA, as polymer and 1.4-micron silica (SiO₂) and 70-nm titanium dioxide (TiO₂) powders as core particles were employed as the coating model for the investigation. As a benign alternative to toxic organic liquid solvents, a supercritical fluid (SCF) mixture of carbon dioxide (CO₂) mixed with ethanol cosolvent, was used to dissolve PLGA in the preparation of coating solution. With the use of SCF solvent, disposals of environmentally hazardous wastes from the process and denaturation of therapeutic agents in the product could be avoided. Rapid expansion of supercritical solution (RESS) process was utilized to produce polymer particles, which can be used for coating, as well as to generate polymer-coated microsize or nanosize particles. PLGA was dissolved in supercritical carbon dioxide (SC-CO₂) to form a supercritical solution at 25 MPa and 313 K. Ethanol, up to 23.8 wt.%, was added to SC-CO₂ to enhance the PLGA solubility. The charged amount of PLGA in SC-CO₂ with 23.8 wt.% ethanol was approximately 0.15 wt.% of the supercritical solution. The RESS process was performed by spraying supercritical solution through a capillary nozzle to ambient air, leading to precipitation of well-dispersed PLGA particles. The average particle size of the precipitated PLGA particles ranges from 55 to 330 nm, depending on the ethanol concentration. For particle coating, SiO₂ and TiO₂ core powders were suspended in the supercritical solution before performing the expansion. The precipitation of PLGA particles accompanying with deposition of the precipitated particles on the core particle surface, solvent evaporation and disintegration of agglomeration of the core particles resulted in formation of coated particles in the form of both individual particles and agglomerates. The thickness of the coating layer was non-uniform but could be estimated to be around 10 to 100 nm