Post-marketing biopharmaceutical evaluation of dipyrone tablets: reference, generic and similar medicines

ABSTRACT

Introduction: Dipyrone is a potent analgesic and antipyretic registered in the Brazilian List of Essential Medicines. Furthermore, it is strategically indicated in special cases, such as the palliative treatment of dengue, chikungunya, zika and COVID-19. Post-marketing problems have been identified for this drug, such as quality non-conformities, resulting in frequent withdrawals of medicines containing dipyrone by Anvisa. Objective: To investigate the quality and pharmaceutical equivalence of dipyrone tablets (reference, generics and similar), commercially available in Salvador-Bahia. Method: An experimental study was carried out using methodologies described in the Brazilian Pharmacopoeia 6th edition monograph of sodium dipyrone tablets. Three different brands were analyzed (one generic, two similar and one reference), all collected in Salvador-Bahia. In addition, an alternative analytical method by UV spectrophotometry was developed for the analysis of sodium dipyrone tablets, validated based on RDC No. 166/17. Results: The reference, generic and similar sodium dipyrone tablets met the requirements for identification and characteristics tests. A similar drug sample did not meet the dissolution test and only two generic samples were satisfactory for interchangeability. The assay pharmacopoeial method for dipyrone sodium tablets showed problems related to the analyst's subjectivity and method uncertainty. The proposed alternative method proved to be selective, linear, precise, accurate, and robust, and indicated for the quantification of dipyrone in tablets. Conclusions: From the results obtained, it was observed that post-marketing monitoring of medicines with a population high consumption pattern, such as dipyrone, can signal issues to be investigated by health surveillance, with the objective of supporting its mission that is to protect population's health.