Development of a Novel Milling System Using Supercritical Carbon Dioxide for Improvement of Dissolution Characteristics of Water-Poorly Soluble Drugs.

The aim of this study is to develop a novel milling system using supercritical carbon dioxide (SC-CO) for the improvement of dissolution characteristics of water-poorly soluble drugs. SC-CO possesses high potential in the application of nanotechnology, due to the attractive properties of SC-CO fluid such as cheap, inert and non-polluting. In addition, SC-CO has density comparable to a liquid, viscosity similar to a gas, and high diffusion capacity. Most of all, carbon dioxide exists as gas in room temperature and pressure, which enables the removal of fluid instantaneously. In this study, a novel method of milling using SC-CO was proposed to produce fine-drug particles. SC-CO milling was conducted and its performance was compared with the ones by various milling methods such as jet milling, dry milling and wet milling. A comparison on the effect of each milling medium on its milling performance, drug size distribution, and particle morphology was conducted. Operating variables of the SC-CO milling system were also investigated to clarify the factors affecting the milling properties and to improve drug release characteristics of water-poorly soluble drugs.