| abstract |
A continuous method of preparing submicron particles of a therapeutic or diagnostic agent comprises the steps of continuously introducing the agent and rigid grinding media into a milling chamber, contacting the agent with the grinding media while in the chamber to reduce the particle size of the agent, continuously removing the agent and the grinding media from the milling chamber, and thereafter separating the agent from the grinding media. In a preferred embodiment, the grinding media is a polymeric resin having a mean particle size of less than 300 νm. In another preferred embodiment, the agent, grinding media and a liquid dispersion medium are continuously introduced into the milling chamber. In a further embodiment, the agent and grinding media are recirculated through the milling chamber. The method enables the use of fine grinding media, e.g., of a particle size of less than about 300 νm, in a continuous grinding process which provides extremely fine particles of the agent, e.g., particles less than 100 nm in size, while avoiding problems, e.g., separator screen plugging, associated with prior art processes requiring the separation of agent from the grinding media in the milling chamber. |