Comparative impact of stirring and shearing in drug dissolution testing with usp paddle and crescent-shaped spindles

Abstract

A new crescent-shaped spindle has been proposed to address artefacts found with the USP Paddle spindle. Because of improved stirring and mixing environment within dissolution vessels resulting in improved product-medium interactions, the crescent-shaped spindle provides a more appropriate dissolution test. Diltiazem immediate- (IR) and extended-release (ER) tablets and capsules were used as model drug products to demonstrate that the appropriate dissolution rate may be obtained using a single and lower spindle rotation speed of 25 rpm,rather than product-dependent higher rotation speeds of 75 and 100 rpm with the USP Paddle.The inability to establish appropriate dissolution rate using single rpm for these two products using USP spindle appears to be because of its well documented artefacts of poor stirring and mixing environment in the vessels.There was no evidence of a crushing or harsh stirring environment using the crescent-shaped spindle,as compared to the USP Paddle spindle. This appears to confirm that increased dissolution rate using crescent-shaped spindle is because of the improved stirring environment. In addition,this study provides further evidence that products with different release characteristics (e.g., IR vs ER) may be analyzed using a single experimental condition (crescent-shaped spindle at 25 rpm) unlike the use of the USP Paddle spindle,which requires product dependent multiple test conditions.Thus,the use of the crescent-shaped spindle appears to provide a better alternative for improved dissolution testing and,in particular, for comparative purposes.