Effect of hydrodynamic environment on tablets dissolution rate.

Abstract

The main objective of this research was to develop an experimental method to apply well-defined flow fields to solid dosage forms, to study the rate process underlying tablet dissolution, and to better understand the role of external hydrodynamic condition on mass transfer rate and film thickness during dissolution. Two drugs models, Theophylline (class 1) and Naproxen (class 2), were selected and formulated into conventional tablets containing 105 mg Theophylline or 300 mg Naproxen using the wet granulation method. Tablets were tested for dissolution using both the basket and paddle methods at different rotational speed of 25, 50, 75, and 100 rpm. In general, the paddle method gave higher dissolution rates than the basket method and as the velocity of rotation was increased, drug release was also increased. Six different paddles and a tablet holder were designed and used to test dissolution rate. The rate of dissolution was dependent on the tablet surface area exposed to the dissolution medium, and on the shape, diameter, and area of the paddles used. Theophylline tablets showed increased mass transfer rate and decreased film thickness as basket rotation speed was increased. At 25 rpm, the mass transfer coefficient was 0.684 x 10(-4) cm/sec and film thickness was 12.003 x 10(-2) cm; at 100 rpm, the mass transfer coefficient was 3.884 x 10(-4) cm/sec and film thickness was 2.114 x 10(-2) cm. Paddle values tested at the same speed showed higher mass transfer coefficient and lower film thickness for Theophylline and Naproxen tablets. P values obtained by modification of the Stokes-Einstein equation showed that diffusion is the rate-limiting step to drug release and not mass transfer. This study demonstrated that hydrodynamic condition, type of dissolution testing used, and design of the paddles have an effect on dissolution rate, mass transfer rate, and the film thickness underlying the dissolution process.