Milling of Organic Solids in a Jet Mill. Part 1: Determination of the Selection Function and Related Mechanical Material Properties

Abstract

Abstract The particle size distribution of pharmaceutically active materials and other fine chemicals determines the performance of the final product to a large extent. Often milling of these particles is necessary. It is not possible to determine the milling conditions solely on the basis of the particle size distribution of the starting material, because the (mechanical) properties of the material also determine the desired milling conditions. It is often not possible to optimize milling conditions experimentally because the amount of material available is frequently highly limited. A theoretical approach towards predicting the best milling conditions is needed. The purpose of this study was to develop a method to predict the desired milling conditions given a specific (organic) solid material. The selection function and the breakage distribution function are usually the starting points in modeling the milling process. The selection function is the parameter that includes the material and mill properties. Dimensional analysis made it possible to correlate the selection function with material properties. A set of theories available in the literature enable prediction of the material properties. For different compounds (lactose, paracetamol, a steroidal compound, and two heterocyclic compounds) the selection functions were calculated. The calculations predict differences: lactose reduces slowly in size, while one of the heterocyclic compounds shows the most intense fracture.