Dissolution of USP prednisone calibrator tablets: Effects of stirring conditions and particle size distribution

Abstract

We investigate the effect of stirring conditions on the dissolution of United States Pharmacopoeial Convention (USP) prednisone calibrator tablets. The experiments are performed in an automated USP-II dissolution test apparatus. For this study we use a special paddle-propeller, which can be changed from an ordinary paddle to either a pulling or pushing propeller by changing the angle of the paddle blades. According to the dissolution curves obtained we find that the fastest dissolution, and hence best stirring at a certain stirring frequency, is obtained when the blades of the paddle-propeller is about +30°. This setting corresponds to a pushing, downward flow in the centre of the vessel. We show that the shape of the dissolution curves is similar to that expected from a mix of two different fractions of particles, provided that the stirring is sufficiently intense: one fraction, approximately 60 wt.%, with small particles, and one fraction with large particles. The weight of a large particle is about 100–250 times that of a small. We derive a mathematical expression, based on the cube root law, for the dissolution curves. The expression is fitted to the experimental dissolution curves to investigate the variation of key parameters with stirring and temperature.