Simultaneous Estimation of Sacubitril and Valsartan Combination of Drug in Tablet Dosage Form Using Hydrotropy by UV Spectrophotometry

Sacubitril/valsartan, traded under the brand name Entresto between others, is a fixed-dose combination medication for use heart failure. Sacubitril is a neprilysin inhibitor (A prodrug) and is used in combination with valsartan to reduce the risk of cardiovascular events in patients with chronic heart failure. It is anti - hypertensive drug. Valsartan is an Angiotensin Receptor Blocker (ARB) that may be used to treat a variety of cardiac conditions including hypertension, diabetic nephropathy and heart failure. Two UV-spectrophotometric methods have been developed and validated for simultaneous estimation of Sacubitril and Valsartan in a tablet dosage form. The first method employed solving of simultaneous equations based on the measurement of absorbance at two wavelengths, 226.0 nm and 254.0 nm, 𝜆max for Sacubitril and Valsartan, respectively. The second method was absorbance ratio method, which involves formation of Q-absorbance equation at 240 nm (isoabsorptive point) and also at 254 nm (𝜆max of Valsartan). The methods were found to be linear between the range of 4-12 𝜇g/mL for Sacubitril and 2-10 𝜇g/mL for Valsartan using Methanol as solvent. The mean percentage recovery was found to be 96.68%and 101.89% for the simultaneous equation method and 100.2% and 104.53% for the absorbance ratio method, for sacubitril and valsartan respectively. It could be concluded from the results obtained in the present investigation that the two methods for simultaneous estimation of sacubitril and valsartan in tablet dosage form are simple, rapid, accurate, precise and economical and can be used, successfully, in the quality control of pharmaceutical formulations and other routine laboratory analysis. The reviewed highlights various analytical techniques such as high-performance liquid chromatography (HPLC), ultra- performance liquid chromatography (UPLC), UV Spectroscopy, high per-formance thin layer chromatography (HPTLC), liquid chromatography coupled to tandem mass spectrometry (LC- MS), RP-HPLC and other chromatographic method used. The combination of these drugs with different method was examine and the commonly use of the drugs in hypertensive.

Development and validation of UV-Spectrophotometric and RP-HPLC method for simultaneous estimation of Metformin and Doxycycline in bulk and synthetic mixture

A simple, rapid, sensitive, accurate and precise UV spectrophotometric and isocratic RP-HPLC method have been developed for simultaneous estimation of Metformin and Doxycycline in bulk and synthetic mixture. Spectrophotometric estimation was done by two methods. First method was Q-absorbance ratio method, where two wavelengths 236 nm (λmax of Metformin) and 248 nm (Iso-absorptive point) were used. The second method was first derivative method. In this method the zero-crossing point of Metformin was selected at 282 nm and for Doxycycline, it was 232 nm. The solvent used was methanol in both the above UV-spectrophotometric methods. Metformin and Doxycycline showed good linearity in the series of 1-9 µg/ml and 2-20 µg/ml respectively by both the two methods with an excellent correlation coefficient (r2≥0.998). In RP-HPLC method, the chromatographic separation was achieved on Luna Phenomenex C18 (150 mmХ6 mm, 5 µm) analytical column. A mixture of Acetonitrile: Phosphate buffer (50 mM): Triethylamine (TEA): Tetrahydrofuran (THF) (30:66:2:2) pH adjusted to 2.1 with orthophosphoric acid was used as the mobile phase, at a flow rate of 1 ml/min and at detector wavelength 248 nm. The retention time of Metformin and Doxycycline was found to be 3.561±0.0017 and 5.574±0.0131 minutes respectively. A linear response was observed over the concentration range 4-64 µg/ml of Metformin and 5-80 µg/ml of Doxycycline. All the three methods were validated in accordance to ICH guidelines for linearity, accuracy, precision, LOD and LOQ. The proposed methods were effectively utilized for the concurrent estimation of Metformin and Doxycycline in synthetic mixture. Keywords: Metformin, Doxycycline, Q-absorbance ratio method, First derivative method, RP-HPLC

Q-Absorbance Ratio Spectrophotometric Method for the Simultaneous Estimation of Metformin Hydrochloride and Voglibose in Tablet Dosage form

A new, simple, accurate, precise and reproducible UV-Spectrophotometric method is being developed for the simultaneous estimation of Metformin Hydrochloride and Voglibose in tablet dosage form. The stock solutions were prepared in methanol. The λmax for Metformin Hydrochloride and Voglibose were found to be248 nm and 287nm respectively. The Metformin Hydrochloride and Voglibose obeyed Beer’s law in concentration range of 8-16µg/ml and 4-20µg/ml respectively. Results of analysis of absorbance ratio method were analysed and validated for various parameters according to ICH guidelines for accuracy, precision, linearity, robustness, LOD and LOQ. The proposed method is highly sensitive, precise and accurate, therefore can be used for intended purpose.

Development and Validation of Q-Absorbance Ratio by UV-Spectrophotometric Method for Simultaneous Estimation of Metformin and Empagliflozin in Bulk and Combined Dosage Form

Advantages of simultaneous stability studies are the identification of new degradation products, to understand mutual induction and/or inhibition of rates of degradation and to analyze the degradation products of both drugs. Various ultraviolet spectroscopic and high performance liquid chromatographic assay methods were reported for the estimation of metformin, sitagliptin, pioglitazone, glimepiride and simvastatin individually and in combination with other drugs. All the above reported methods were based on the estimation of metformin, sitagliptin, pioglitazone, glimepiride and simvastatin alone or in combination with other drugs. The degradation products were generated and successfully separated by the developed and validated high performance liquid chromatographic methods for the estimation of the selected anti-diabetic drug combinations. The aim of the study was to develop and validate of Q-Absorbance Ratio UV-Spectrophotometric Method for Simultaneous Estimation of Metformin and Empagliflozin in Bulk and Combined Dosage Form. Keywords: Metformin, Method Development, Validation, Empagliflozin, UV-Spectrophotometer.

SIMULTANEOUS SPECTROPHOTOMETRIC DETERMINATION OF DAPAGLIFLOZIN AND SAXAGLIPTIN IN FIXED DOSE COMBINATION (FDC) BY Q-ABSORBANCE RATIO METHOD

A simple Q-absorbance ratio method have been developed for the determination of dapagliflozin (DAPA) and saxagliptin (SAXA) in fixed dose combination (FDC) using UV-Visible spectrophotometer. In this method, the UV spectra of DAPA and SAXA were overlaid to obtain wavelength at isosbestic point (λiso) of 217.6 nm and at absorption maximum (λmax) of DAPA at 224.2 nm, which are involved in the formation of Q-absorbance equation. Validation of method was done according to ICH guidelines. DAPA and SAXA obeyed Beers law in the concentration range of 2-25 µg/mL and 5-25 µg/mL, respectively. Good accuracy of method was determined by recovery studies and found to be in the range of 103.1-104.6% for DAPA and 97.7-102.4% for SAXA. This method has shown good precision (%RSD < 2.0). Statistical analysis like one-way ANOVA and student t-test were conducted and the reported method was accurate. This method was found to be simple, cheap, eco-friendly accurate and precise and can be used for routine analysis of DAPA and SAXA in FDC for testing regularly in manufacturing units.

A VALIDATED STABILITY INDICATING UV-SPECTROPHOTOMETRIC SIMULTANEOUS ESTIMATION OF ROSUVASTATIN CALCIUM AND FENOFIBRATE IN BULK AND PHARMACEUTICAL FORMULATION

Objective: The present work deals with the development and validation of the absorbance ratio method for the estimation of rosuvastatin calcium and fenofibrate in bulk and pharmaceutical formulation. Studied forced degradation characteristics of bulk and pharmaceutical formulation as per stability guidelines. Methods: The bulk and pharmaceutical formulation studied by the absorbance ratio method. It is the ratio of absorbances at two selected wavelengths. One wavelength is the isoabsorptive point and another wavelength is λ max of one of the components. From the overlay spectra of the two drugs, ROS and FEN showed the isoabsorptive point at 249.5 nm. The second wavelength used was 287 nm, which was the λ max of FEN. Results: The drugs obeyed Beer's law and showed a good correlation. The correlation coefficient for the ROS was 0.999 and for FEN 0.999. The RSD for intraday precision was 0.57 for ROS and 0.057 for FEN. The interday precision was 0.05 for ROS and 0.03for FEN, respectively. The detection limit and quantification limit were found to be 0.048 and 0.14 μg/ml for ROS and 0.069 and 0.21μg/ml for FEN, respectively. More degradation was found in acid hydrolysis and photostability degradation. Conclusion: A simple, precise, accurate, validated, stability-indicating method for simultaneous estimation of rosuvastatin calcium and fenofibrate in bulk and pharmaceutical formulation has been developed.