MAY 2021 www.dissolutiontech.com *Corresponding author dx.doi.org/10.14227/DT280221PGC2 In Vitro Biopharmaceutical Equivalence of Carbamazepine Sodium Tablets Available in Lima, Peru Angel T. Alvarado 1* , Ana María Muñoz 2 , María R. Bendezú 3 , Juan J. Palomino-Jhong 3 , Jorge A. García 3 , César André Alvarado 4 , Erick A. Alvarado 4 , Gaby Ochoa-Pachas 5 , Mario Pineda-Pérez 5 , and Mario Bolarte 5 1 International Network for Research in Pharmacology and Precision Medicine, School of Human Medicine, San Ignacio de Loyola University, Lima, Peru. 2 Research Unit in Nutrition, Health, Functional Foods and Nutraceuticals, Universidad San Ignacio de Loyola, Lima Peru. 3 Faculty of Pharmacy and Biochemistry, San Luis Gonzaga National University of Ica, Ica, Peru. 4 Faculty of Human Medicine, University of San Martín de Porres, Lima, Peru. 5 Peruvian Association of Immunogenomics and Personalized Medicine, Lima, Peru. e-mail: eaa.alvarado@hotmail.com ABSTRACT Carbamazepine is an antiepileptic iminostilbene that is dispensed from multiple sources in Peru without bioequivalence studies. The biopharmaceutical equivalence of two generic (A and B) and one commercial brand (C) of carbamazepine sodium as compared to the innovator drug was determined by an in vitro study of commercial 200-mg tablets, following the guidelines of the Biopharmaceutical Classification System. Hardness, weight, friability, and content were evaluated for compliance with official specifications. A United States Pharmacopeia (USP) dissolution apparatus 2 (paddle) was used at with 900 mL of medium (pH 1.2, 4.5, and 6.8) at 75 rpm and 37 ± 0.5 °C. Samples (5 mL) were withdrawn at 5, 10, 15, 30, 45, 60, and 90 minutes and analyzed in a UV spectrophotometer at 288 nm. The studied drugs did not release 85% of the active pharmaceutical ingredient within 30 minutes in any media. When compared to the innovator brand using the similarity factor (f2), product A was < 50 at all three pH levels; B was < 50 at pH 4.5, and C was < 50 at pH 1.2 and 4.5. For all products, dissolution efficiency was 56.1–84.3% and mean dissolution time was 18.0–47.5 min. Despite meeting the official specifications for quality control tests, the evaluated samples are not in vitro biopharmaceutical equivalents with the innovator brand based on the dissolution profiles (f2 < 50). KEYWORDS: Quality control, carbamazepine, bioequivalent drugs, drug interchangeability, dissolution INTRODUCTION Relative bioavailability studies demonstrate the bioequivalence of high health risk drugs that belong to class 2 (low solubility and high permeability) and class 4 (low solubility and low permeability) (1, 2). Through in vitro studies, the bioequivalence of class 1 (high solubility and high permeability) and class 3 (high solubility and low permeability) drugs is demonstrated, according to the Biopharmaceutical Classification System (BCS) using three dissolution media at pH 1.2, pH 4.5 and pH 6.8 (2–4). In vitro dissolution tests must simulate the physiological conditions of the gastrointestinal tract to predict optimal absorption (5). Carbamazepine (5-H- dibenzazepine-5-carboxamide) is an iminostilbene-type class 2 drug derived from tricyclic antidepressants, with a pKa of 2.3 due to the N of the dibenzazepine ring and a pKa of 13.9 due to the free NH2 group of the carboxamide (6, 7). So, in vitro bioequivalence studies do not apply but in vitro biopharmaceutical equivalence studies can be used to evaluate the biopharmaceutical phase of the tablets, following the BCS guidelines for class 1 and 3. The BCS