(392d) Novel Aspects of the Production of Microsuspensions and Nanosuspensions of Poorly Water Soluble Drugs by Wet Media Milling

Micronization and nanoparticle production of poorly water soluble drugs was investigated using single wet milling equipment in the attrition and stirred media modes of milling. The drug particles in the median size range of 200nm-2μm were prepared by changing the design and operating conditions of a Micros mill. The dynamics of the wet milling process coupled with stabilization of the produced finer particles has been elucidated. It was found that breakage due to mechanical stresses and aggregation due to insufficient stabilization are two competing mechanisms which together control the dynamics of the wet milling process. The screening study of four different classes of stabilizers with six different poorly water soluble drugs was done in the attritor mill. The results indicated that steric stabilization could stabilize the drugs better than the electrostatic stabilization. In addition the existence of different optimum polymer concentrations for the stabilization of microsuspensions and nanosuspensions was indicated. A new method of producing stable nanosuspensions was also developed by a slight change in processing conditions of the stirred media mill. The process change in the method of polymer addition provided effective stabilization and breakage of drug suspensions leading to narrower particle size distribution, short processing time and lowering the power consumption of the milling process.