Pharmaceutical Composition of Valsartan: β-Cyclodextrin: Physico–Chemical Characterization and Anti-Hypertensive Evaluation

Abstract

Valsartan, a water-insoluble drug, is mainly used in the treatment of hypertension albeit with reduced oral bioavailability. The aim of work was to develop a valsartan:β-cyclodextrin (VAL:β-CD) pharmaceutical composition in order to improve its water solubility and bioavailability. The VAL:β-CD complexes were prepared by the kneading, solid dispersion and freeze-drying methods, of which the freeze-drying method (FDY) was found to be the best to prepare an inclusion complex. A physical mixtyure PM was also prepared. Complexes were characterized by thermal analysis, Fourier transformed- infrared (FTIR) spectroscopy, Powder X-ray diffractometry, intrinsic dissolution and NMR (2D-ROESY). Phase-solubility analysis showed AL-type diagrams with β-cyclodextrin (β-CD). Microcalorimetric titrations suggested the formation of 1:1 inclusion complex between VAL and β-CD. The apparent stability constants K1:1 calculated from phase-solubility plots were 165.4 M-1 (298 K), 145.0 M-1 (303 K) and 111.3 M-1 (310 K). In vivo experiments in rats showed that reduction in arterial pressure for the FDY complex is better than with valsartan used alone. The better activity of FDY can be attributed to the higher solubility of valsartan after inclusion in the cyclodextrin cavity, as suggest by the intrinsic dissolution studies.

Pharmaceutical Composition of Hydrochlorothiazide:β-Cyclo-dextrin: Preparation by Three Different Methods, Physico-Chemical Characterization and In Vivo Diuretic Activity Evaluation

“…In developed countries, heart disease and stroke are the first and the third-ranked causes of morbidity and mortality, respectively [ 1 ]. Pharmacological treatment of hypertension consists in the use of drug therapies including association or not of diuretics, beta-blockers, calcium channel blockers, angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor (AT1) antagonist (ARA) [ 1 , 2 , 3 , 4 ].…”

The Problem of Dynamic Process Manifestation in Identification of Organic Compounds by NMR Spectroscopy

“…Проиллюстрируем влияние заторможенного вращения вокруг амидной связи на вид ЯМР-спектров на примере валсартана. Валсартан представляет собой антагонист рецептора ангиотензина II и применяется при лечении гипертонической болезни, застойной сердечной недостаточности, повышает выживаемость больных с острым инфарктом миокарда [33]. В спектре 1 Н валсартана (ДМСО-d6, T = 27 °С) присутствуют Z-и E-конформеры в соотношении 60/40 (рис.…”

“…Соотношение Z-и Е-конформеров соединений с амидной связью в различных растворителях [19,20]. Однако заторможенность конформационных переходов в молекуле валсартана сохраняется не только при действии растворителя, но и при комплексообразовании с β-циклодекстрином [33]. Наш вывод о том, что присутствующие в растворах различных растворителей конформеры являются ротамерами вокруг амидной связи, подтверждается данными спектров ROESY.…”

Preparation and Evaluation of Valsartan Liquid Filling Formulations for Soft Gels

“…From the literature review, it is clearly evident that most of the works were published with cyclodextrin inclusion complexation [ 7 ], solid dispersions [ 8 , 9 ], self-microemulsifying drug delivery system [ 10 ], and other solubilization technologies for improving the solubility, dissolution, bioavailability, and pharmacokinetic properties of VAL. However, Mbah CJ studied the solubility of VAL in solvents like ethyl alcohol and propylene glycol and also in some surfactants [ 11 , 12 ].…”