264611 A Microhydrodynamic Analysis of Wet Stirred Media Milling for Production of Stable Drug Nanoparticle Suspensions
One way to improve the bioavailability of poorly water-soluble drugs is to reduce particle size of drug crystals down to nanoscale via wet stirred media milling. An increase in total surface area per mass loading of the drug and in specific surface area as well as reduced external mass transfer resistance allow a faster dissolution of the poorly-water soluble drug from nanocrystals. To prevent aggregation of nanoparticles, polymers and surfactants are dissolved in water acting as stabilizers via adsorption onto the drug crystals.
In the last two decades, ample experimental data were generated in the area of nanoparticle suspension production via media milling (e.g. [1,2]). Recirculation mode of milling operation, where the nanoparticle suspension in a holding tank continuously circulates through the stirred media mill, has been commonly used in lab, and commercial scales. To explain the impact of some of the processing parameters such as rotor speed, media (bead) loading, bead size, etc., stress intensity and stress number concepts have been widely used , which do not account for the complex microhydrodynamics in the mill and the effects of the suspension viscosity. In the present work, the impact of various processing parameters on the process dynamics was studied using Griseofulvin as a model drug. As a major novelty, we analyze and interpret the impact of processing parameters via a microhydrodynamic model . Our analysis suggests that the product of the average bead oscillation velocity and the frequency of single-bead oscillation appears to be a key empirical parameter that governs the breakage dynamics. Physical interpretation of this combined empirical parameter is discussed.
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