Capecitabine: An In-vitro Comparison between the Branded Xeloda? 500 Mg and its Intended Copy Capeda 500 Mg

Abstract

Introduction: Dissolution is an example of in-vitro test which can be used to identify formulations that may present potential bioequivalence problems. It is defined as the amount of substance that goes into solution per unit time under standardised conditions of liquid/solid interface, solvent composition and temperature. It is considered one of the most important tools to predict the in-vivo bioavailability and in some cases replacing clinical studies to determine bioequivalence. Aim: To compare the differences in the dissolution behaviour between two anticancer formulations, Xeloda ® 500 mg (reference product) and Capeda 500 mg (test product). Methods: Four replicates for each batch of the tested medicines were carried out using a PT-DT70 dissolution tester (Pharma Test) to detect any differences in their dissolution behaviour. Samples at nine time intervals were tested according to the US Pharmacopeia with the rate of dissolution determined by ultraviolet spectrophotometery. Results: All the tested medicines complied with the pharmacopoeial specifications, the EMA and the FDA guidance for industry when achieved 85% dissolution in 60 minutes. However, Capeda 500 mg (test product) showed slower, different and incomplete dissolution rate compared to Xeloda ® 500 mg (reference product) at both 60 and 120 minutes. Other visual differences in the weight, size, clarity of solution, presence of un-dissolved residue and particles during the dissolution test were also detected. Conclusion: Results in this study clearly raise a question about the interchangeability between Xeloda ® 500 mg and its Intended copy Capeda 500 mg. Awareness of these scientific concerns should be considered when a clinical choice between these two drugs is required. Differences between the innovator and copy medicines with regard to pharmacokinetics, clinical efficacy and safety may exist. Thereby, patients' monitoring after performing drug substitution of these two medicines is strongly recommended.