Scale-up of Mixing Process for Low Drug Content Formulation

Abstract

A scale-up method of a low drug content mixing process in a V-type blender was proposed. Acetaminophen was used for the model drug, and the low drug mixing experiment was conducted using three scales of V-type blenders under the same fill level and Froude (Fr) number. However, the uniformity of mixtures could not correspond with the mixing time or the total revolution number. To find the optimum scale-up factor, discrete element method (DEM) simulations of three different scales of V-type blender mixing were conducted, and the total travel distance of particles under the different scales was calculated. The uniformity of drug content obtained from the scale-up experiments was well correlated with the mixing time determined by the total travel distance. It was found that the scale-up DEM simulation based on the travel distance of particle was valid for the low drug content mixing scale-up processes.