MALCORE®, a manufacturing technology of drug-containing particles (DCPs) for coating, consists of a 2-step melt granulation process. The drug-layering process in the technology is important for determining the characteristics of the resulting DCPs. However, the effect of the manufacturing conditions of the drug-layering process on particle characteristics has not been clarified. The aim of this study was to investigate the effect of the manufacturing conditions for MALCORE® on particle characteristics using the design of experiments (DoE) method.

A high-shear granulator was used in the drug-layering process, and the product temperature, melt granulation time, and blade rotation speed were selected as input factors for the DoE. The available yield, d10 and d50, flowability, particle strength, and drug dissolution of DCPs were evaluated, and the relationship between the manufacturing conditions and particle characteristics was clarified using statistical methods.

The available yield and d50 were affected by all manufacturing conditions while the particle strength was affected only by the blade rotation speed. Drug dissolution was unaffected by the manufacturing conditions. The predicted and measured values in the design space of the manufacturing conditions constructed based on these results were almost identical, thereby indicating the validity of the DoE.

The results of this study revealed the effect of manufacturing conditions on particle characteristics for a unique manufacturing technology MALCORE®, in which the drug is layered on the core particles by melt granulation. The findings provide useful information for the implementation of MALCORE® in pharmaceutical formulation development.