Investigation of dissolution behavior of diclofenac sodium extended release formulations under standard and biorelevant test conditions

Abstract

Background: Dissolution characteristics of four extended release (ER) generic formulations of diclofenac sodium were examined. Aim: The aim of this study was to compare the drug dissolution behavior of diclofenac ER generics to clarify whether the products are characterized by comparable dissolution characteristics under the applied test conditions. Methods: The investigations were performed in the USP apparatus 2 and in the new biorelevant dissolution stress test device. Results: The experiments yielded striking differences between the generic formulations. Applying USP apparatus 2 it was noticed that the dissolution profiles of the products were distinctly affected by the stirring rate. Using the biorelevant dissolution stress test device susceptibility of the products to biorelevant stresses was observed. Change of pH within the experiments reduced the dissolution rates of all formulations and distinctly influenced their dissolution characteristics. Conclusion: The study demonstrates clearly the divergences in the dissolution behavior among the generic ER formulations of diclofenac sodium. The observed susceptibility of the tested dosage forms toward biorelevant stress bears in our interpretation the risk to cause unwanted fluctuations in drug plasma concentration profiles.

Keywords:

• Biorelevant dissolution testing
• diclofenac extended release tablets
• dissolution stress test
• HPMC matrix tablet
• pH change

Acknowledgments

The authors thank the staff members of the precision mechanical shop of the Faculty of Mathematics and Natural Sciences (Rüdiger Kuhr, Henry Bürth, Günter Arndt, Frank Scheffter, Joahim Schmidt, and Gerhard Schulz) for their excellent technical assistance. This work was funded by the German Federal Ministry of Education and Research (InnoProfile 03IP612).

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.