A mathematical model to predict the size of the pellets formed in freeze pelletization techniques: Parameters affecting pellet size*

A mathematical model was developed based on the theory of drop formation to predict the size of the pellets formed in the freeze pelletization process. Further the model was validated by studying the effect of various parameters on the pellet size such as viscosity of the pellet forming and column liquids, surface/interfacial tension, density difference between pellet forming and column liquids; size, shape, and material of construction of the needle tips and temperatures maintained in the columns. In this study, pellets were prepared from different matrices including polyethylene glycols and waxes. The column liquids studied were silicone oils and aqueous glycerol solutions. The surface/interfacial tension, density difference between pellet forming and column liquids and needle tip size were found to be the most important factors affecting pellet size. The viscosity of the column liquid was not found to significantly affect the size of the pellets. The size of the pellets was also not affected by the pellet forming liquids of low viscosities. An increase in the initial column temperature slightly decreased the pellet size. The mathematical model developed was found to successfully predict the size of the pellets with an average error of 3.32% for different matrices that were studied. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association