Melt granulation in a high shear mixer: optimization of mixture and process variables using a combined experimental design

Melt granulation of a formulation of theophylline, containing lactose, microcrystalline cellulose and hydroxypropylmethylcellulose as excipients, was investigated in a 10 l high shear mixer as an alternative method to the wet granulation process, using polyethylene glycol 6000 as melting binder. The experimentation was planned by combining mixture and factorial designs in order to study the effect of two process variables, namely impeller speed and massing time, and of excipient mixture composition on two characteristics of the granules. By the response surface methodology, it was possible to find the mixture composition and the processing conditions leading to granulates with optimal granule characteristics.