Sandeep Sonawane

Development and Validation of Stability-Indicating Method for Estimation of Chlorthalidone in Bulk and Tablets with the Use of Experimental Design in Forced Degradation Experiments

Chlorthalidone was subjected to various forced degradation conditions. Substantial degradation of chlorthalidone was obtained in acid, alkali, and oxidative conditions. Further full factorial experimental design was applied for acid and alkali forced degradation conditions, in which strength of acid/alkali, temperature, and time of heating were considered as independent variables (factors) and % degradation was considered as dependent variable (response). Factors responsible for acid and alkali degradation were statistically evaluated using Yates analysis and Pareto chart. Furthermore, using surface response curve, optimized 10% degradation was obtained. All chromatographic separation was carried out on Phenomenex HyperClone C 18 column (250 × 4.6 mm, 5 μ), using mobile phase comprising methanol : acetonitrile : phosphate buffer (20 mM) (pH 3.0 adjusted with o-phosphoric acid): 30 : 10 : 60% v/v. The flow rate was kept constant at 1 mL/min and eluent was detected at 241 nm. In calibration curve experiments, linearity was found to be in the range of 2–12 μg/mL. Validation experiments proved good accuracy and precision of the method. Also there was no interference of excipients and degradation products at the retention time of chlorthalidone, indicating specificity of the method.

Design, synthesis and molecular modeling studies of few chalcone analogues of benzimidazole for epidermal growth factor receptor inhibitor in search of useful anticancer agent

In the present investigation, few 3-(substitutedphenyl)-1-[2-(1-hydroxy-ethyl)]-1H-benzimidazol-1-yl)prop-2-en-1-ones are EGFR antagonist are designed, by molecular docking analysis. The synthesized compounds were tested for their in vitro anticancer activity by propidium iodide fluorescent assay and Trypan blue viability assay against colorectal cancer cell lines (HCT116) and non-small cell lung cancer cell lines (H460). Human Epithelial Kidney cell lines (HEK) are used as normal cell lines for studying effect of drug on non-cancerous cells within human body. Evaluation of cytotoxic studies of synthesized compounds CHL(1-8) reveal that compound CHL1 [IC50=7.31 and 10.16 μM against HCT116 and H460 cell lines respectively, by PI assay] and CHL8 [IC50=12.52 and 6.83 against HCT116 and H460μM cell lines respectively] possess promising cytotoxic activity.

Development and Validation of RP-HPLC Method for Simultaneous Estimation of Saxagliptin and Dapagliflozin in Tablets

A simple, accurate, precise and selective RP-HPLC method was developed and validated for simultaneous estimation of Saxagliptin (SAXA) and Dapagliflozin (DAPA) in tablet dosage form. Both drugs were separated on Phenomenex Hyperclone C18 column (250 ×4.6 mm, 5μ) using methanol: 20 mM phosphate buffer (pH3.0) (70: 30, v/v) in an isocratic mode at flow rate of 1 mL/min. Chromatographic determination was carried out at wavelength of 225nm. SAXA and DAPA were eluted at 4.70 and 6.45min, respectively. The method was found linear in the range of 2–12 μg/mL and 4–24 μg/mL for SAXA and DAPA, respectively. The method was validated for linearity, accuracy, precision and selectivity. The developed method can be used for routine analysis of SAXA and DAPA tablets.

Application of factorial design approach in development and evaluation of self microemulsifying drug delivery system (SMEDDS) of mebendazole

Self microemulsifying drug delivery systems (SMEDDS) are defined as isotropic mixtures of natural or synthetic oils, surfactants and co-solvents/co-surfactants. Upon mild agitation followed by dilution in aqueous media, such as GI fluids, these systems can form fine oil in water o/w microemulsion. The purpose of this study was to formulate SMEDDS containing mebendazole. Labrafil M2125 CS (an oil), Tween 20 (a surfactant), and Maisine 35-1 (a cosurfactant) were used to formulate SMEDDS. Effect of concentrations of oil and surfactant on emulsification process and in vitro drug release (percent cumulative drug release) was studied using 32 factorial design. Multiple regression analysis data and response surfaces obtained showed that viscosity increased significantly with increasing amount of co-surfactant. Whereas, decrease in emulsification time, it may decreases average droplet size of resultant microemulsion and rapid drug release. The drug release from the formulation increased with increasing amount of surfactant concentration increases solubility of drug in system. Prepared SMEDDS produced acceptable properties of immediate-release dosage forms. The L5 formulation was found to be optimized on basis of high percent cumulative drug release. And it is evaluated by globule size and zeta potential indicates globule size is in micrometer range and good stable formulation. It may expect to increase the bioavailability of mebendazole as solubility enhances.

Development and Validation of RP-HPLC Method for simultaneous estimation of Telmisartan, Amlodipine Besylate and Hydrochlorthiazide in their tablet dosage form

To treat the second stage high blood pressure, physicians prefers the combination drug therapy consisting of two or more anti-hypertensive agents. Among these, telmisartan with amlodipine besylate, telmisartan with hydrochlorthiazide as well as triple drug therapy consisting of amlodipine besylate, telmisartan and hydrochlorthiazide are commonly prescribed. In the present paper, a simple, accurate and precise RP-HPLC method was developed for the estimation of amlodipine besylate, telmisartan and hydrochlorthiazide in bulk and combined dosage form. All these three drugs were successfully separated and resolved from each other on C18 kinetex column (250 × 4.6 mm, 5 μ), using acetonitrile: 20mM phosphate buffer (pH 3.0) (60: 40%, v/v) as a mobile phase at a flow rate of 1 mL/min. The detection was performed at 258 nm. The developed method was further validated as per ICH Q2 (R1) guidelines.

Development of a RP-HPLC method for separation of ezetimibe in presence of atorvastatin caclium and simvastatin and its application for qunatitation of tablet dosage forms

A single, simple, accurate and precise RP-HPLC method has been developed for the estimation of ezetimibe in presence of atorvastatin calcium and simvastatin in bulk and marketed combined formulations. The chromatographic separation was achieved on C18 column (250 × 4.6 mm, 5 μ) using Acetonitrile: water 70: 30 v/v as a mobile phase at flow rate of 1.2 mL/min. The separation was achieved in isocratic mode and the detection was performed at 242 nm. Further the developed method was validated as per the ICH Q2 (R1) and applied for quantitation of atorvastatin calcium-ezetimibe and ezetimibe-simvastatin in tablet formulations.

Development and Validation of RP-HPLC method for simultaneous Estimation of Metformin HCl and Gliclazide

A new, simple and validated RP-HPLC method was developed for simultaneous estimation of Metformin HCl (MET) and Gliclazide (GLZ). The separation was achieved by using mobile phase Methanol: 10 mM Phosphate buffer (pH 3) 70: 30% v/v on Kinetics C18 column (250 × 4.6 mm, 5μ). The flow rate was 1 ml/min. The detection was carried out at wavelength 230 nm. The retention time of MET and GLZ was found to be 2.20 min and 4.67 min, respectively. Calibration curves for MET and GLZ were found to be linear in the range of 10–60 μg/ml and 2–12 μg/ml, respectively. The proposed method was validated as per ICH guideline Q2 (R1). The validation parameters studied were linearity, accuracy, precision, specificity and robustness. All validation parameters were found within the acceptable range.