Dissolution of mesalazine modified release tablets under standard and bio-relevant test conditions

Abstract

Objectives: For the treatment of inflammatory bowel disease, the development of pH responsive modified release dosage forms is one of the most common approaches to achieve targeted drug delivery. In this study, the dissolution behaviour of eight different modified release (MR) products containing 800 mg mesalazine was investigated.

Methods: The performance of the products was compared under simulated fasted state conditions using the paddle apparatus as well as the dissolution stress test device mimicking mechanical stress events of bio-relevant intensity.

Key findings: The dissolution behaviour of the eight tested different pH-responsive MR tablets containing 800 mg mesalazine was dependent on the test conditions. Phases of mechanical stress with physiological intensity influenced the dissolution characteristics and caused in some cases accelerated drug release indicating possible dose dumping.

Conclusion: The study demonstrates that besides the investigation of the pH dependency of drug release, the characterisation of the mechanical robustness of the dosage forms is an essential factor determining the dissolution characteristics of such pH-dependent targeted modified release tablets. The susceptibility of 800 mg mesalazine MR tablets towards mechanical stress may be one reason for undesired drug delivery in vivo.

Keywords: bio-relevant dissolution testing; burst release mesalazine; carbonate buffer; dissolution stress test; dose dumping.