title: Study of valsartan interaction with micelles as a model system for biomembranes.
abstract: In this study, the interaction of valsartan (VAL), an angiotensin II receptor antagonist, with cationic surfactant cetyltrimethylammonium bromide (CTAB) was investigated. The effect of cationic micelles on spectroscopic and acid-base properties of VAL was carried out using UV spectrophotometry at physiological conditions (pH 7.4). The binding of VAL to CTAB micelles implied a shift in drug acidity constant (pK(a)(water)-pK(a)(micelle)=1.69) proving the great affinity of VAL dianion for the positively charged CTAB micelle surface. To quantify the degree of VAL/CTAB interaction, two constants were calculated by using mathematical models: micelle/water partition coefficient (K(x)) and drug/micelle binding constant (K(b)). The decrease of K(x) with VAL concentration, obtained by using pseudo-phase model, is consistent with an adsorption-like phenomenon. From the dependence of differential absorbance at lambda=295 nm on CTAB concentration, by using mathematical model that treats the solubilization of VAL dianion as its binding to specific sites in the micelles (Langmuir adsorption isotherm), the binding constant (K(b)=(2.50+/-0.49)x10(4)M(-1)) was obtained. Binding constant VAL/CTAB was also calculated using micellar liquid chromatography (MLC).
authors.affiliation: Institute of Pharmaceutical Chemistry and Drug Analysis, Faculty of Pharmacy, Vojvode Stepe 450, P.O. Box 146, 1100 Belgrade, Serbia.
authors.forename: O
authors.initials: O
authors.lastname: Cudina
authors.forename: J
authors.initials: J
authors.lastname: Brborić
authors.forename: I
authors.initials: I
authors.lastname: Janković
authors.forename: K
authors.initials: K
authors.lastname: Karljiković-Rajić
authors.forename: S
authors.initials: S
authors.lastname: Vladimirov
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000737:chemistry*; D000077286:Cetrimonium; D002593:Cetrimonium Compounds / Q000737:chemistry*; D002853:Chromatography, Liquid / Q000379:methods; D008567:Membranes, Artificial; D008823:Micelles; D013056:Spectrophotometry, Ultraviolet; D013777:Tetrazoles / Q000737:chemistry*; D014633:Valine / Q000031:analogs & derivatives* / Q000737:chemistry; D000068756:Valsartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D002593:Cetrimonium Compounds; D008567:Membranes, Artificial; D008823:Micelles; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine; D000077286:Cetrimonium