Continuous synthesis of nano-drug particles by antisolvent crystallization using a porous hollow-fiber membrane module.

The synthesis of nano-size drug particles by antisolvent crystallization using a porous hollow fiber membrane provides promising benefits such as the capability of continuous operation, low energy input, and ease of scale-up for a variety of industrial processes. Porous hollow fiber membranes have also been shown to produce more efficient mixing than conventional mixing equipment mostly because in mixing binary fluids, they provide sufficient mixing time, retention time, and a large contact interface for the drug solution and the antisolvent, allowing for the precise control of nucleation and crystal growth necessary to form nano-size particles. This study reports an experimental and numerical approach to obtain a further understanding of the fundamental principles of antisolvent crystallization using a porous hollow fiber membrane. This includes producing a particle size-controlled drug nanosuspension experimentally using a commercial microfiltration (MF) pencil scale module, and a numerical analysis of mixing behavior using a computational fluid dynamics (CFD) simulation. From the results obtained, a nanosuspension of a model drug, Indomethacin, with particles of average diameter 0.320 µm was prepared. Furthermore, this nanosuspension has higher stability and a much lower tendency to agglomerate as compared to simple mixing of the anti-solvent and drug solution. Results from the numerical simulation showed that micromixing is possible using the porous hollow fiber membrane even under the most compromising conditions.

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-CO2) for the improvement of dissolution characteristics of water-poorly soluble drugs. SC-CO2 possesses high potential in the application of nanotechnology, due to the attractive properties of SC-CO2 fluid such as cheap, inert and non-polluting. In addition, SC-CO2 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-CO2 was proposed to produce fine-drug particles. SC-CO2 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-CO2 milling system were also investigated to clarify the factors affecting the milling properties and to improve drug release characteristics of water-poorly soluble drugs.