In vitro equivalence evaluation of betahistine generic medicinal products as a tool potentially determining the efficacy of pharmacotherapy

Abstract

To compare release parameters of various betahistine drugs in vitro using a comparative dissolution kinetics test. Objects of research are solid dosage forms (tablets) containing betahistine in a dose of 24 mg permitted for medical use in the Russian Federation. A method of comparative dissolution kinetics test was carried out as follows. The study was performed on a paddle stirrer at a speed of 50 rpm in three different pH dissolution media (pH 1.2, 4.5, 6.8), simulating the main sections of the digestive tract in which the active ingredient was decomposed, released and absorbed. This was performed in a quality controlled environment using a citrate buffer solution with pH 6.8. The time points for sampling the medium were 10 min, 15 min, 20 min and 30 min. The results of betahistine release were significant (RSD<10%) for all time points, except the first time point (RSD<20%). Regardless of pH, there was a complete release (≥85% over 15 minutes, <10%) of betahistine from betaserc, 24 mg, tablets (manufactured by Mylan Laboratories SAS). The dissolution profiles of betahistine in other investigational drugs did not show complete drug release (parameter <85% in 15 minutes, <10%) in different pH media. Therefore, dissolution profiles of the studied drugs were not comparable to the reference profile. Starting from 10 minutes, the reference drug of betahistine (betaserc, 24 mg) has a consistently higher release at different pH levels (representing the various stages of gastric digestion), vs. other studied generic analogues showing significantly lower levels of betahistine release. None of the studied drugs were found to be equivalent in vitro.