Small-Scale Spherical Granulation Using a Planetary Centrifugal Mixer.

Abstract

A concise spherical granulation method is required to prepare extemporaneously granules remanufactured from oral dosage forms for administration to individuals who cannot swallow tablets or capsules. In this study, we determined the feasibility of spherical granulation using a planetary centrifugal mixer. A model formulation, 20% ibuprofen (IBP) granules, was prepared using a lactose/cornstarch (7 : 3, w/w) mixture or D-mannitol as diluents, and changes in granule characteristics (mean diameter (d50), distribution range of granule size (span), and yield) were evaluated according to the amount of water added and the granulation time. The amount of water was assessed using the plastic limit value as measured using a digital force gauge. We successfully produced granules, and larger amounts of water and longer granulation times resulted in larger d50 values and smaller span values. The optimal granulation time was 45 s and the optimal water contents were 70 and 67.5% of the plastic limit value for the lactose/cornstarch mixture and D-mannitol, respectively. When compared to commercial 20% IBP granules, powder X-ray diffraction and differential scanning calorimetry analyses showed that the granulation process did not alter the crystallinity of the drug. Thus, this novel granulation method using a planetary centrifugal mixer may be a promising technique for compounding in pharmacies and in pharmaceutical manufacturing.