The Evaluation of Valsartan Biopharmaceutics Properties

Abstract

Background: Solubility, intestinal permeability and dissolution are the main factors that govern the rate and extent of drugs absorption and are directly related to bioavailability. Biopharmaceutics Classification System (BCS) is an important tool which uses in vitro results for comparison with bioavailability in vivo (biowaiver). Valsartan is widely used in the treatment of hypertension and shows different BCS classification in the literature (BCS class II or III). Objective: This work proposes the study of valsartan biopharmaceutics properties and its BCS classification. Methods: High Performance Liquid Chromatography (HPLC) method was developed and validated to quantify the drug in buffers pH 1.2, 4.5 and 6.8 respectively. Valsartan solubility was determined in these three different media using shake flask method and intrinsic dissolution rate. Evaluation of dissolution profile from coated tablets was conducted. Results: The low solubility (pH 1.2 and 4.5) and high solubility (pH 6.8) were observed for both solubility methods. Permeability data reported from the literature showed that valsartan is a low permeability drug. Valsartan presented the rapid release profile only in pH 6.8. Conclusion: We defined that valsartan is a class IV drug, in disagreement with what has been published so far. It is important to emphasize that the conditions considered here are indicated to define the biopharmaceutics classification by regulatory agencies.

Exploring in vitro solubility of lamotrigine in physiologically mimetic conditions to prospect the in vivo dissolution in pediatric population

“…The solubility equilibrium (S eq ) condition, which is determined from a saturated solution containing excess solids where the solution and solid are in equilibrium, was adopted when the last two measurements were similar. For comparison purposes, the 24‐h solubility test was also performed for the FaSSIF‐V2 blank (de Castro et al., 2020; GlaxoSmithKline, 2020).…”

Novel crystal forms of Entresto: a supramolecular complex of trisodium sacubitril/valsartan hemi-pentahydrate

“…Valsartan exists in amorphous and crystalline solid forms. 28 It exhibited higher bioavailability in the cocrystal than regular valsartan tablets. Hence, valsartan 26 mg, 51 mg, and 103 mg in the Entresto combination are equivalent to 40 mg, 80 mg, and 160 mg in single-dose formulations, respectively.…”

In Vivo Predictive Dissolution and Biopharmaceutic-Based In Silico Model to Explain Bioequivalence Results of Valsartan, a Biopharmaceutics Classification System Class IV Drug

“…VALS is a BCS class IV [8,9] weak acid drug with low solubility and permeability; thus, its systemic exposure depends on both factors, that is, permeability and its release from the dosage form. In two previous studies, two combination products of VALS and HCTZ (class III drug) failed to show BE.…”