Improvement of Solubility and Stability of Valsartan by Hydroxypropyl-\boldbeta-Cyclodextrin

Journal of Inclusion Phenomena (Impact Factor: 1.43). 01/2006; 54(3):289-294. DOI: 10.1007/s10847-005-9004-y

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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    ABSTRACT: The objective of the present study was to develop self micro emulsifying formulation (SMEF) of valsartan to improve its oral bioavailability. The formulations were screened on the basis of solubility, stability, emulsification efficiency, particle size and zeta potential. The optimized liquid SMEF contains valsartan (20% w/w), Capmul MCM C8 (16% w/w), Tween 80 (42.66% w/w) and PEG 400 (21.33% w/w) as drug, oil, surfactant and co-surfactant, respectively. Further, Liquid SMEF was adsorbed on Aerosol 200 by spray and freeze drying methods in the ratio of 2 : 1 and transformed into free flowing powder. Both the optimized liquid and solid SMEF had the particle size <200 nm with rapid reconstitution properties. Both drying methods are equally capable for producing stable solid SMEF and immediate release of drug in in vitro and in vivo conditions. However, the solid SMEF produced by spray drying method showed high flowability and compressibility. The solid state characterization employing the FTIR, DSC and XRD studies indicated insignificant interaction of drug with lipid and adsorbed excipient. The relative bioavailability of solid SMEF was approximately 1.5 to 3.0 folds higher than marketed formulation and pure drug. Thus, the developed solid SMEF illustrates an alternative delivery of valsartan as compared to existing formulations with improved bioavailability.
    07/2013; 2013:909045. DOI:10.1155/2013/909045
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    ABSTRACT: For the quality evaluation of raw materials, the influence of various types of solvents on the polymorphic crystallization behaviors and dissolution rates of two sources of valsartan (VAL) from China and India was investigated. Samples were prepared by recrystallization from water or organic solvents, such as acetonitrile, acetone and ethanol, using methods with and without heating. Recrystallization behaviors were characterized by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). Scanning electron microscopy (SEM) was also used to observe the morphology of samples. The dissolution rate of recrystallized samples in water was evaluated and compared to the original VAL sample. There were significant differences in morphology, crystal structure and dissolution rate among the samples recrystallized using organic solvents. VAL was transformed into another polymorphic form by the solvents and recrystallization conditions. These physical properties of VAL also differed between the two sources of VAL. Thus, the physicochemical differences of raw materials should be carefully considered in early dosage formulation approaches.
    Archives of Pharmacal Research 07/2012; 35(7):1223-30. DOI:10.1007/s12272-012-0713-7 · 1.75 Impact Factor
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    ABSTRACT: A photostability study of Valsartan (VAL) is reported. Exposure of the drug to UV-vis radiation (λ > 320 nm) yielded two previously unknown compounds, which were detected by HPLC. Preparative amounts of the new potential degradation products (DP-1 and DP-2) were obtained by submitting VAL bulk drug to extensive photodegradation. The impurities were isolated by preparative normal phase column chromatography. Analytical information from the infrared, nuclear magnetic resonance and mass spectral data of the degradation products revealed their structures as N-[2'-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-N-isobutylpentanamide (DP-1) and N-(diazirino[1,3-f]phenanthridin-4-ylmethyl)-N-isobutylpentanamide (DP-2). DP-1 arose from decarboxylation of VAL, while DP-2 results from further loss of nitrogen from the tetrazole motif of DP-1, with concomitant cyclization to yield a tetracyclic diazacyclopropene derivative.
    Journal of pharmaceutical and biomedical analysis 08/2011; 56(1):16-22. DOI:10.1016/j.jpba.2011.04.017 · 2.83 Impact Factor