Development and in vitro/in vivo evaluation of immediate release perindopril tablets

Abstract

Perindopril erbumine (PE) is a BCS (Biopharmaceutics Classification System) class 3 drug with high solubility and low permeability. It is an inhibitor of the enzyme that converts angiotensin I (Angiotensin Converting Enzyme, ACE) into angiotensin II as well as causing the degradation of the vasodilator bradykinin into an inactive heptapeptide. The aim of this study was to develop an alternative drug product by using a different salt of perindopril and to evaluate the bioequivalence between PE, not still licensed, and perindopril arginine (PA), licensed in many countries, and to prepare PE tablets by using direct compression method. Many different formulations were prepared, among which F3-coded formulation was only selected due to releasing of 98.03% active substance at 45th minute. Bioequivalence study was planned as a cross-designed, randomized, open-labeled, single-dose, single-center study and conducted in 24 male healthy volunteers via peroral route. The results of bioequivalence study were evaluated for Perindopril and Perindoprilat according to C_max, t_max and AUC criteria. The geometric mean ratios (90% CI) of perindopril and perindoprilat followed test and reference drug were calculated for AUC_0–t and C_max, 105.946% (100.218–112.002%) and 110.437% (102.534–118.948%); 109.542% (98.364–121.992%) and 115.729% (101.031–132.565%), respectively. The 90% confidence intervals of them were found within the standard bioequivalence range (80–125%).

• Bioavailability
• hypertension
• in vitro studies
• in vivo studies
• perindopril erbumine

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.