Formulation and Bioequivalence of Two Valsartan Tablets After a Single Oral Administration

Abstract

The aim of this study is to assess the quality of Valzan® tablet (160 mg, valsartan immediate release test formulation) by comparing its pharmacokinetic parameters with Diovan® tablet (160 mg, valsartan reference formulation). Valzan® tablets were prepared according to a dry granulation method (roll compaction). To assess the bioequivalence of Valzan® tablets a randomized, two-way, crossover, bioequivalence study was performed in 24 healthy male volunteers. The selected volunteers were divided into two groups of 12 subjects. One group was treated with the reference formulation (Diovan®) and the other one with the generic Valzan®, with a cross-over after the drug washout period of 14 days. Blood samples were collected at fixed time intervals and valsartan concentrations were determined by a validated HPLC assay method. The pharmacokinetic parameters AUC0–48, AUC0–∞, Cmax, Tmax, Ke and T1/2 were determined for both the tablets and were compared statistically to evaluate the bioequivalence between the two brands of valsartan, using the statistical model recommended by the FDA. The analysis of variance (ANOVA) did not show any significant difference between the two formulations and 90% confidence intervals (CI) fell within the acceptable range for bioequivalence. Based on this statistical evaluation it was concluded that the test tablets (Valzan®) is well formulated, since it exhibits pharmacokinetic profile comparable to the reference brand Diovan®.

Histological and immunohistochemical study on nitric oxide synthase and effects of angiotensin receptor blockade in early phase of diabetes in rat kidney

“…Taking into consideration the fact that valsartan is a wellknown antihypertensive drug, the dose used was the least effective dose to minimize the blood pressure-lowering effect on the animals as much as possible [9].…”

Development of a Dissolution Method to Compare Tablet Formulations Containing Valsartan/Amlodipine

“…This formulation provides improved control of blood pressure with reduced cardiovascular and renal risk and minimal adverse effects. Exforge is the first commercially available combination of these drug classes as a fixed-dose regimen containing 5 or 10 mg AM and 160 or 320 mg VS (7,9,11). The present work reports the development and validation of a reversed-phase HPLC method for the estimation of VS/AM in tablets and the development of a validated method for the dissolution of these tablets.…”

“…Several methods are available in the literature to measure the concentration of VS and AM in individual and combined products (21)(22)(23). The method was validated for parameters like system suitability, selectivity, linearity, range, precision, accuracy, and robustness.…”

“…It is a dihydropyridine calcium channel blocker (CCB) used in the treatment of hypertension and is well-absorbed (bioavailability of 64-80%) with no food effect after oral administration. The maximum plasma level is reached within 6-8 h. The elimination phase occurs biexponentially with a long terminal half-life of 30-50 h. AM is extensively bound to plasma proteins (94-98%) and is metabolized in the liver by CYP3A4 (7)(8)(9). It is classified as either BCS Class I or Class III and has high solubility, but its measured permeability is low (10).…”

Preclinical Pharmacokinetic Evaluation of Valsartan Floating Tablets Formualted Using Cross Linked Starch Urea - A New Modified Starch

“…It has a short biological half-life of 3-6 hrs. [8] Hence sustained release floating tablet formulation is needed for valsartan to enhance its oral bioavailability and to prolong its therapeutic effect, to reduce dosage frequency and to increase patient compliance.…”