Valsartan inclusion by methyl-β-cyclodextrin: thermodynamics, molecular modelling, Tween 80 effect and evaluation

Renu Chadha; Madhu Bala; Poonam Arora; D V S Jain; Raghuvir R S Pissurlenkar; Evans C Coutinho

doi:10.1016/j.carbpol.2013.12.047

Valsartan inclusion by methyl-β-cyclodextrin: thermodynamics, molecular modelling, Tween 80 effect and evaluation

Carbohydr Polym. 2014 Mar 15:103:300-9. doi: 10.1016/j.carbpol.2013.12.047. Epub 2013 Dec 24.

Authors

Renu Chadha¹, Madhu Bala², Poonam Arora², D V S Jain³, Raghuvir R S Pissurlenkar⁴, Evans C Coutinho⁴

Affiliations

¹ University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India. Electronic address: renuchadha@pu.ac.in.
² University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
³ Department of Chemistry, Panjab University, Chandigarh 160014, India.
⁴ Department of Pharmaceutical Chemistry, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai 400098, India.

PMID: 24528733
DOI: 10.1016/j.carbpol.2013.12.047

Abstract

The rationale of present study is to investigate the effect of Tween 80 on encapsulation ability of valsartan (VAL) by methyl-β-cyclodextrin (M-β-CD) and to determine the exact mode of binding. Phase solubility studies indicated 1:1 stoichiometry between VAL and M-β-CD both in the presence and absence of Tween 80. The NMR and molecular modelling studies indicated the insertion of both aromatic and aliphatic regions of VAL into the M-β-CD cavity suggesting the coexistence of two 1:1 complexes in equilibrium with each other. The stability constants, K1 (aromatic) and K2 (aliphatic), were enhanced in the presence of Tween 80 as evident by higher value of stability constants (K1 1992.0M(-1), K2 1864.0M(-1)) for ternary system in comparison to binary system (K1 1741.6M(-1), K2 1499.2M(-1)). Efficacy of ternary complex was established by significant decrease in the systolic blood pressure of deoxycorticosterone acetate (DOCA) induced hypertensive rats.

Keywords: Enthalpy; Molecular modelling; NMR; Permeability; Solubility; Valsartan.