Valsartan

To develop and validate simple, rapid, linear, accurate, precise and economical UV Spectroscopic method for estimation of Valsartan in tablet dosage form. The drug is freely soluble in analytical grade Ethanol, Methanol and Acetonitrile. The drug was identified in terms of solubility studies and on the basis of melting point done on Melting Point Apparatus of Equiptronics. It showed absorption maxima were determined in diluent Methanol: Water (50:50) ratio. The drug obeyed the Beer’s law and showed good correlation of concentration with absorption which reflect in linearity. The UV spectroscopic method was developed for estimation of Valsartan in tablet dosage form and also validated as per ICH guidelines. The drug is freely soluble in analytical grade Ethanol, Methanol, Acetonitrile and sparingly soluble in water. So, the analytical grade Methanol: water (50:50) is used as a diluent in method. The melting point of Valsartan was found to be 115-116?C (uncorrected). It showed absorption maxima 250 nm in Methanol: Water (50:50) ratio. On the basis of absorption spectrum the working concentration was set on 20µg/ml (PPM). The linearity was observed between 10-30 μg/ml (PPM). The results of analysis were validated by recovery studies. The recovery was found to be 98.75, 101.00 and 99.17% for three levels respectively. The % RSD for precision was found to be 0.35%. A simple, rapid, linear, accurate, precise and economical UV Spectroscopic method has been developed for estimation of Valsartan in tablet dosage form. The method could be considered for the determination of Valsartan in quality control laboratories. Keywords: Valsartan, Development, UV Spectrophotometer, Melting Point, Assay Method, Validation, Accuracy, Linearity, Ruggedness, Precision.

The objective of the present research work was to simultaneously separate the anti-hypertensive agents, Amlodipine and Valsartan and develop a validated analytical method for simultaneous quantitative determination of amlodipine and valsartan in tablet dosage form. A simple, rapid, precise and selective chromatographic method was developed and validated for separation and determination amlodipine and valsartan in tablet preparations. The anti-hypertensive agents were analyzed by Symmetry C18, (150 × 3.4 mm, 5 µ), Shimadzu LC-2010CHT Prominence Liquid Chromatograph and a mobile phase constituted of 10 mM Buffer (pH 3.0): methanol (50:50, v/v). The flow rate was 1.0 mL/min and the analysis were performed using UV- Vis detector at 237nm. The anti-hypertensive agents, Amlodipine and Valsartan were separated within 10 min. Amlodipine and Valsartan showed retention time of 5.06 and 8.28 min respectively. The drugs were found to obey Beer’s law in the concentration range of 100 ppm of amlodipine and 128 ppm of valsartan. The developed assay method is selective, precise and accurate. The method has been successfully applied for determination of Amlodipine and Valsartan in pharmaceutical combination tablet dosage form. This developed method is sensitive, fast and simple with excellent peak symmetry and high resolution.

Solubility is an important physicochemical factor affecting absorption of drug and its therapeutic effectiveness. Drugs having poor aqueous solubility present one of the major confronts better absorption for good bioavailability of such drugs. The purpose of this study was to prepare and characterize solid dispersions of the poorly water soluble antihypertensive agent valsartan with water soluble carriers such as Kolliphor P 407, Kolliphor P 188, Kolliwax GMS II, Kolliphor HS15, HPMC AS and Soluplus in proportions viz. 1:1, 1:3, 1:5 (Drug: Carrier) with addition of 2% SLS to improve its aqueous solubility and rate of dissolution by solvent evaporation technique. All the formulations showed marked improvement in the solubility behavior and improved drug release. From all the formulations  SD6 was found to be optimized formulation  using soluplus as carrier based on the solubility and dissolution studies. The results obtained showed that the aqueous solubility and rate of dissolution was significantly improved when formulated in solid dispersion as compare to pure drug.

A simple, accurate, and precise UV spectrophotometric method has been developed and validated for simultaneous estimation of Cilnidipine and Valsartan in synthetic mixture. The estimation of drugs was done by Second Order Derivative spectrophotometric method using 219 nm and 227 nm wavelength. Methanol was used as a solvent. The Linearity was obtained in the concentration range of 2-10 µg/ml for Cilnidipine and 5-25 µg/ml for Valsartan with R2 0.9994 and 0.9980 respectively. Accuracy was determined by recovery studies and showed % recovery between 98 to 102 % for both the drugs. The LOD and LOQ values of Cilnidipine were found to be 0.33 and 1.01 and for Valsartan values were found to be 0.18 and 0.55. The developed method was validated as per the ICH Guidelines Q2 (R1).

A simple, specific, accurate and precise reverse phase high performance liquid chromatographic (RP-HPLC) method was developed with high sensitivity for determination of Valsartan and Hydrochlorothiazide drugs in combined dosage forms. The separation was achieved on Zorbax CN (25 cm x 4.6 mm, 5 µm) at flow rate of 1.8 ml/min with 70: 30 mixture of phosphate buffer: acetonitrile (pH 6) as the mobile phase. The quantification was achieved with PDA detector at 265 nm. The injection volume was 20 μl. The retention times of Valsartan and Hydrochlorothiazide were 6.04 min and 2.27 min, respectively. The method was validated for linearity, precision, specificity, robustness and recovery according to the ICH guidelines. The linearity of response for Valsartan and Hydrochlorothiazide were assessed by analysis of five independent levels of calibration curve in range of 20-100 µg/ml and 2-10 µg/ml respectively. The recovery data was between 98.77-99.73% and 98.75-100.56% for Valsartan and Hydrochlorothiazide respectively. The limit of detection and quantification for Valsartan were 0.98 and 2.97μg/ml respectively and for Hydrochlorothiazide were 0.18 and 0.57μg/ml, respectively. The method was found to be simple and highly sensitive and can be useful in the routine quality control of Valsartan and Hydrochlorothiazide in bulk manufacturing and pharmaceutical dosage forms.

Dissolution is a valuable qualitative tool to asses the biological availability and batch to batch consistency. Discriminative dissolution mediums are highly desirable to differentiate the dissolution profiles of two identical products which are varied in their composition, formulation technique, manufacturing process and site of manufacturing. The objective of present investigation is to develop discriminative dissolution medium for valsartan by using two different marked formulations named as VALZAAR and VALENT. The dissolution studies were performed in four dissolution mediums (0.1N HCl (pH 1.2), pH 4.5 acetate buffer, pH 6.8 phosphate buffer and distill water) at three different agitation speeds (50, 75,100 RPM). Model independent approaches such as difference factor (f1) and a similarity factor (f 2) were used to compare dissolution profiles. Among all the cases in pH 6.8 phosphate buffer at 100 rpm drug releases at faster rate and best suited to maintain sink conditions. Irrespective of other cases pH 4.5 acetate buffer at 50 rpm was considered as a discriminative dissolution medium because of its lesser similarity factor and higher difference factor. From the present experimental investigation the rate of dissolution was found to be influenced by pH of the dissolution medium and speed of the agitation. The usage of 4.5 acetate buffer at 50 rpm was found to be a discriminative dissolution medium for valsartan tablets.