Improvement of Solubility and Stability of Valsartan by Hydroxypropyl-\boldbeta-Cyclodextrin
ABSTRACT Aim of the present work was to investigate the effect of hydroxypropyl-β-cyclodextrin (HP-β-CD) on the solubility, dissolution
rate and stability of Valsartan (VAL), a drug used orally for the treatment of hypertension. Phase solubility studies demonstrated
the ability of the HP-β-CD to complex VAL and to increase drug solubility. The dissolved amount of VAL increased linearly
with the addition of HP-β-CD according to an AL type plot. The apparent stability constant of the complex, calculated supposing a 1:1 stoichiometry, was 296±7M−1. VAL/HP-β-CD interactions were also studied by 13C-NMR spectroscopy. Equimolar VAL/HP-β-CD solid systems were prepared by physical-mixing and freeze-drying, and their properties
in the solid state studied by DSC and FT-IR analysis. The results provided clear indications of the formation of a new solid
phase corresponding to the inclusion complex in the freeze-dried sample. The dissolution profiles of the drug from each solid
system were affected by its physico-chemical properties, the freeze-dried being the most rapidly dissolving form. The thermal
stability of the complex was studied, also determining the number and identity of the decomposition products of the drug.
The stability studies revealed that the VAL/HP-β-CD complex significantly decreases the rate of VAL degradation. These results
suggest that CD technology would be a very useful method to overcome the solubility and the stability problems of VAL.
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Article: Analysis of Sartans: A Review.[Show abstract] [Hide abstract]
ABSTRACT: The risk of cardiovascular diseases is closely related to hypertension, high cholesterol levels, and diabetes. When these risk factors appear together they are referred to as a metabolic syndrome. In the treatment of cardiovascular diseases, a combination of antihypertensive, hypolipemiant, and antidiabetic drugs is often applied. Diuretics (chlortalidone, hydrochlorothiazide, etc.) and angiotensin II receptors antagonist (sartans) are used to control hypertension, whereas statins (fluvastatin, simvastatin, etc.) are used to reduce cholesterol levels. This review is concerned with methods for the analysis of sartans in various matrices, such as pharmaceutical formulations, environmental and biological samples, and discusses the current status of stability studies of sartans . It also presents analytical methods for the simultaneous determination of sartans, diuretics, and statins. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.Journal of Pharmaceutical Sciences 11/2013; · 3.13 Impact Factor
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ABSTRACT: The solid state properties and dissolution behavior of binary systems of cefdinir (CEF) with hydroxypropyl-β-cyclodextrin (HP-β-CD) were investigated. CEF-HP-β-CD interaction in the solution state was studied by phase-solubility analysis and demonstrates the ability of HP-β-CD to complex with CEF giving AL type profile with 65.28 ± 1.3 M(-1) stability constant. The freeze drying technique was adopted to prepare binary systems of CEF with HP-β-CD in 1:1 molar ratio. The solid inclusion was characterized by fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray powder diffractometry (XRD), and scanning electron microscopy (SEM). Aqueous solubility of CEF-HP-β-CD inclusion complex was 2.36-fold of pure CEF. The dissolution profiles of inclusion complexes were determined and compared with those of CEF alone and their physical mixtures. The dissolution rate of inclusion complex was superior than the CEF alone. These approaches indicated that CEF was able to form an inclusion complex with HP-β-CD, and the inclusion compounds exhibited different spectroscopic features and properties.Drug Development and Industrial Pharmacy 11/2013; 39(11):1638-1643. · 2.01 Impact Factor
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ABSTRACT: A self micro-emulsifying drug delivery system (SMEDDS) has been developed to enhance diffusion rate and oral bioavailability of Flurbiprofen. The solubility of Flurbiprofen was checked in different oils, surfactants, and co-surfactants and ternary phase diagrams were constructed to evaluate the micro-emulsion domain. The Flurbiprofen SMEDDS was prepared using Capmul MCM (oil), Tween 80 (surfactant), and polyethylene glycol 400 (co-surfactant). The particle size distribution, zeta potential, and Polydispersity index were determined and found to be 12.3 nm, −0.746, and 0.138, respectively. Diffusion rate of Flurbiprofen was measured by in vitro dialysis bag method using phosphate buffer pH 6.8 as diffusion media. Developed high-performance liquid chromatography method was used to determine drug content in diffusion media. Oral bioavailability of Flurbiprofen SMEDDS was checked by using mice model. Results of diffusion rate and oral bioavailability of Flurbiprofen SMEDDS were compared with those of pure drug solution and of marketed formulation. Diffusion of Flurbiprofen SMEDDS showed maximum drug release when compared to pure drug solution and marketed formulation. The area under curve and time showed significant improvement as the values obtained were 607 ng h/mL and 1 h for SMEDDS in comparison to 445.36 and 1.36 h for market formulation suggesting significant increase (p<0.01) in oral bioavailability of Flurbiprofen SMEDDS. Keywords: Flurbiprofen, Surfactant, Zeta Potential, Polydispersity Index and Bioavailability.World Journal of Pharmaceutical Research (WJPR). 09/2014; 3(7):105-124.