Milling of pharmaceutical powder carrier excipients: Application of central composite design

Abstract

Pharmaceutical powder carriers are often used to prevent agglomeration of a micronized drug in the co-milling process. Twenty-four pharmaceutical excipients were subjected to preliminary mild milling conditions in this work. Ten of them showed acceptable milling properties with alginic acid, calcium alginate, microcrystalline cellulose (Avicel® 200), carrageenan, and hypromellose having the best particle size reduction without any aggregation while maintaining a narrow span. For the latter five substances, circumscribed central composite design (CCD) evaluating the effect of the factors milling speed and timeon the responses (particle size, particle size distribution) for three milling ball sizes was used to establish optimal milling conditions. For all ten possible factor combinations and each ball size, a quadratic response surface model was used to predict the response variable. For three substances out of five, the best results were achieved using 5-mm balls. Thermal characteristics showed the good stability of excipients under optimized milling conditions.