Dissolution Technologies | NOVEMBER 2009 29 e-mail: motsuka@musashino-u.ac.jp Effect of Paddle-Shaft Position on the Dissolution Rate of Sodium Diclofenac Tablets and the Equivalence Assessment of a Generic Product Mari Fujimoto 1,2,* , Kiyoshi Mihara 2,3,* , James A. Jorgenson 4 , Kuniko Otsuka 5 , Masaki Aburada 2,3 , Tomie Kawada 3 , Junko Ishizaki 1 , Ken-ichi Miyamoto 1 , and Makoto Otsuka 3,6 1 Graduate School of Natural Science and Technology, Kanazawa University, Kakuma, Kanazawa, 920-1192, Japan 2 Research Center for Clinical Pharmacy, Faculty of Pharmacy, Musashino University, Shinmachi 1-1-20, Nishitokyo, Tokyo, 202-8585, Japan 3 Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, Shinmachi 1-1-20, Nishitokyo, Tokyo, 202-8585, Japan 4 Department of Hospital Pharmacy, University of Utah, 50 North Medical Drive, Room A050 SLC, UT 84132-5901 5 Yokohama College of Pharmacy, Matano-cho 601,Totsuka, Yokohama 245-0066, Japan ABSTRACT Dissolution testing is useful for controlling the quality of oral products and rejecting bioinequivalent products. However, several sources of variability in dissolution tests can affect evaluations of quality. The purpose of this study was to investigate the effects of paddle-shaft position on the dissolution rates of a brand-name (BR) and four generic- equivalent (GE), rapid-release tablets of sodium diclofenac. The paddle was shifted 5 mm from the center of the vessel, and the dissolution profiles were compared with that obtained at the central position. Although the GEs had a wide range of variability and significantly different dissolution profiles, they were estimated to be equivalent to the BR when the paddle was set at the center of the vessel. The 5-mm-shifted position significantly increased the dissolution rates of all products with the result that some GEs did not meet the criteria for equivalence. In conclusion, paddle position is potentially a cause of error in GE equivalence assessments. The paddle should be accurately positioned at the center of the vessel in dissolution tests for the equivalence assessment of GEs. INTRODUCTION T he use of generic-equivalent (GE) drugs reduces medical and health-care costs. However, the market share of GEs in Japan is less than in other developed countries (1). While 96% of consumers supported GE usage in a questionnaire provided by the Japan Fair Trade Commission in September 2006 (2), 54% of physicians questioned their quality (3). Therefore, quality assurance is extremely important to eliminate anxiety about the usage of GEs in Japan. GEs must be as safe and effective as brand-name medicines (BRs) and bioequivalent to BRs in human in vivo pharmacokinetic studies. Dissolution testing is a useful tool for the quality control of oral products, and it provides important information concerning bioequiva- lence. However, there are several sources of variability in dissolution testing such as temperature, pH (4, 5), and aeration (6) of the test medium; rotation and agitation of the paddle shaft (4, 7, 8); sample position (4, 9); sample storage conditions (6); and analytical methods (10), which potentially affect decision errors of quality evaluation. Qualification of the test apparatus and procedures is required. Therefore, it is necessary to develop a reliable and precise dissolution test method that is sensitive enough to detect slight differences between GE and BR. In this study, we investigated whether moving the paddle-shaft axis from the center affects the rate of dissolution. Precision glass vessels were used to exclude the effect of the vessel factor on tablet dissolution profiles. Sodium diclofenac in rapid-release tablets was chosen as the model drug and dosage form, because it is highly soluble in water, and its pharmacological effect appears so rapidly that the dissolution rate of the tablet may affect the therapeutic effect of the drug. MATERIALS AND METHODS Materials Bulk powder sodium diclofenac was purchased as a standard material from Sigma Chemical Co. The drugs tested in this study were Voltaren as a reference and four GEs. All products were rapid-release dosage forms that 6 Corresponding author. *These authors contributed equally to this report. diss-16-04-06.indd 29 diss-16-04-06.indd 29 11/25/2009 8:54:55 AM 11/25/2009 8:54:55 AM dx.doi.org/10.14227/DT160409P29