Granulation of Aspirin Sustained-Release Formulation with Hydroxypropyl-methylcellulose as Rate-Controlling Agent

Abstract

Wet granulation using a high-speed mixer was studied with hydroxypropyl-methylcellulose (HPMC) as a rate-controlling polymer and aspirin as a model drug. i) High and low HPMC viscosity both produce granulations with high density; high HPMC content gives small density. ii) At low levels, HPMC viscosity and HPMC content contribute separately and negatively to geometric median diameter; at high levels, the synergistic interaction of these two factors contributes most. iii) At very high viscosity range, the yield does not change as HPMC content increases; at other ranges of HPMC viscosity, yield decreases as HPMC content increases. At any HPMC content level, an HPMC viscosity region gives maximum yield. (iv) Using the optimization statistics methodology, an optimal region of HPMC content and HPMC viscosity was found. Within this region, expected granulations will be produced.