Metformin hydrochloride extended-release tablets: perception of the occurrence of gastrointestinal adverse events and biopharmaceutical evaluation

Diarrhea is a common adverse event at the beginning of metformin hydrochloride use. Extended-release (XR) tablets are an alternative for patients intolerant to the immediate-release formulation. This study evaluated the perception of gastrointestinal adverse events (GAE), quality, and dissolution behavior between reference (R) and generic (G) XR formulations. A prospective cohort study recorded diarrhea, abdominal discomfort, and impact on daily activities using a perception form. R and G were analyzed for quality and dissolution behavior. Among 29 patients, 16 used R (55.2%) and 13 G (44.8%). Both groups presented GAE (diarrhea: R= 8, G= 8; abdominal discomfort: R= 9, G= 7). BMI was significantly associated with the occurrence of GAE regardless of the medications studied. All samples met pharmacopoeial quality standards. The Higuchi model best described the dissolution kinetics of R, and Peppas-Sahlin for G. The dissolution profiles were similar (F2= 67), although the dissolution efficiency differed by more than 10%. Our findings reinforce the interchangeability between reference and generic medicines, providing an effective option for patients with type II diabetes mellitus. This strengthens the principles of the National Generic Medicines Policy in Brazil, contributing to the sustainability of the healthcare system and the democratization of access to essential medicines.

Key words
Diarrhea; Dissolution profile; Flatulence; Nausea; Type II diabetes mellitus