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

• Published in: Pharmaceutical development and technology Vol. 20; no. 6; pp. 684 - 693
• Main Authors: Ölçer, Muharrem, Ölçer, Aysel, İnce, İskender, Karasulu, Ercument
• Format: Journal Article
• Language: English
• Published: England Informa Healthcare 01-01-2015
• Subjects: Adolescent; Adult; Angiotensin-Converting Enzyme Inhibitors - administration & dosage; Angiotensin-Converting Enzyme Inhibitors - blood; Angiotensin-Converting Enzyme Inhibitors - chemistry; Angiotensin-Converting Enzyme Inhibitors - pharmacokinetics; Antihypertensive Agents - administration & dosage; Antihypertensive Agents - blood; Antihypertensive Agents - chemistry; Antihypertensive Agents - pharmacokinetics; Bioavailability; Cross-Over Studies; Drug Liberation; Humans; hypertension; in vitro studies; in vivo studies; Male; Middle Aged; Perindopril - administration & dosage; Perindopril - blood; Perindopril - chemistry; Perindopril - pharmacokinetics; perindopril erbumine; Salts - chemistry; Solubility; Tablets - chemistry; Therapeutic Equivalency; Young Adult; in vivo studies; Bioavailability; hypertension; in vitro studies; perindopril erbumine
• ISSN: 1083-7450; 1097-9867
• DOI: 10.3109/10837450.2014.915568

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%).