Accelerated dissolution testing for improved quality assurance.

Abstract

In pharmaceutical production of controlled release tablets and capsules, a rapid and automated at-line dissolution test for quality assurance of semi-products is advantageous. For effective control of the production, the analysis should not take more than about an hour, without loss of correlation to the ordinary (USP) dissolution test of the final product. For almost a decade, the ACDRA apparatus (ACcelerated Dissolution Rate Analysis) have been used for this purpose at AstraZeneca Tablet Production Sweden (TPS). In this paper, we give examples on different ways to accelerate the dissolution process. We use the USP dissolution calibrator tablets of salicylic acid (non-disintegrating type) to illustrate the strategy. We investigate the accelerated dissolution of the dissolution calibrator tablets, and show how it can be correlated with the dissolution in the ordinary USP-II equipment. The dissolution process was accelerated by variation of temperature, solvent and stirring. For example, we show that by increasing the temperature to 70 degrees C, changing the solvent to water, and increasing the stirring, it is possible to accelerate the dissolution by a factor of 5, without any loss of correlation to the dissolution process in the ordinary test.