THE DEVELOPMENT AND VALIDATION OF A FAST STABILITY INDICATING RP-HPLC METHOD FOR QUANTIFICATION OF LUMEFANTRINE AND ITS ORGANIC IMPURITIES USING CENTRAL COMPOSITE EXPERIMENTAL DESIGN TARAKA RAMESH G., Y. RAJENDRA PRASAD International Journal of Applied Pharmaceutics, 2023 Objective: The objective of the present study was to develop and validate a stability indicating RP-HPLC method for Lumefantrine (LF) and its organic impurities using a central composite design (CCD). Methods: A specific, simple quality control friendly isocratic elution method using reverse phase HPLC was developed for quantification of Lumefantrine (LF) and its organic impurities at a wavelength of 265 nm. The chromatographic separation was achieved on the column of Thermo Hypersil ODS C18 (150x4.6 mm, 3µ) with a buffer containing 0.1percent formic acid and acetonitrile 10:90 v/v as a mobile phase with a flow rate of 1.6 ml/min at 35 °C with a run time of 10 min. Based on the preliminary trials, CCD was employed to check the effect of independent variables such as Acetonitrile ratio (A), Flow rate (B), and Column oven temperature (C). While resolution between Lumefantrine (LF) and Impurity-A (X1), Impurity-A and Impurity-B (X2), and Plate count of Lumefantrine (LF) (X3) were considered as dependent variables and statistical evaluation performed by using design expert software. The optimized conditions were validated as per ICH guidelines. Results: The retention time of LF and its organic impurities were 1.9 min, 3.0, 4.5, and 6.4 min, respectively. Design space was established and desirability was found. LOD and LOQ for the Lumefantrine (LF) and its impurities were established with respect to test concentration. The plotted calibration curves were linear with a regression coefficient of R2>0.99, indicating that the linearity was within the limit. As a part of method validation, the parameters like Specificity with forced degradation, Linearity, Precision, Accuracy, Ruggedness, and Robustness were determined and the results were found to be within the allowable limits. Conclusion: The method developed and validated was found to be suitable for routine analysis and to be used for the measurement of Lumefantrine and its impurities. Since there is no stability indicating the RP-HPLC method with design space was reported in the literature, there is a need to develop quantitative methods under different conditions to achieve improvement in specificity and selectivity.
UTILITY OF QUALITY BY DESIGN APPROACH IN RP-HPLC METHOD DEVELOPMENT FOR QUANTIFICATION OF LAMIVUDINE AND EFFAVIRENZ IN COMBINATION FORMULATION Bhagavan Rajesh Babu KOPPİSETTY, Prof. Y. Rajendra PRASAD, Krishna Manjari Pawar AMGOTH, Srinivasa Rao YARRAGUNTLA, Vasudha DADI, et al. Ankara Universitesi Eczacilik Fakultesi Dergisi, 2023 Objective: For the measurement of lamivudine(LAM) and effavirenz (EVZ) in combination formulation, a uncomplicated and reliable liquid chromatographic approach has been proposed.
 Material and Method: Multivariate optimization of the RP-HPLC method, experimental conditions were accomplished using the design of experiments (DoE). The crucial method parameters were determined by a risk assessment. The mathematical models were created using three independent variables: percentage of acetonitrile, percentage of methanol, and buffer pH. The impacts of these independent elements were thoroughly investigated using the central composite design (CCD), which was utilized to analyze the response surface methodology. 
 Result and Discussion: The LAM and EVZ retention time and resolution were both concurrently optimized using the desirability function. Acetonitrile, methanol, and phosphate buffer (pH 7.0) in the proportions of 40:20:40 v/v each were used in the optimized and anticipated data from the contour diagram, with detection occurring at a wavelength of 215 nm. Baseline separation of both pharmaceuticals with high resolution and a run time of under 6 minutes was accomplished under these ideal conditions. The validated test parameters followed ICH recommendations. As a consequence, the findings demonstrated that the Quality by Design methodology could be successfully used to optimize the RP-HPLC technique for the concurrent quantification of LAM and EVZ.
Antitubercular activity assessment of fluorinated chalcones, 2-aminopyridine-3- carbonitrile and 2-amino-4H-pyran-3- carbonitrile derivatives: In vitro, molecular docking and in-silico drug likeliness studies Surendra Babu Lagu, Rajendra Prasad Yejella, Srinath Nissankararao, Richie R. Bhandare, Venu Sampath Golla, et al. Plos One, 2022 A series of newer previously synthesized fluorinated chalcones and their 2-amino-pyridine-3-carbonitrile and 2-amino-4H-pyran-3-carbonitrile derivatives were screened for their in vitro antitubercular activity and in silico methods. Compound 40 (MIC~ 8 μM) was the most potent among all 60 compounds, whose potency is comparable with broad spectrum antibiotics like ciprofloxacin and streptomycin and three times more potent than pyrazinamide. Additionally, compound 40 was also less selective and hence non-toxic towards the human live cell lines-LO2 in its MTT assay. Compounds 30, 27, 50, 41, 51, and 60 have exhibited streptomycin like activity (MIC~16–18 μM). Fluorinated chalcones, pyridine and pyran derivatives were found to occupy prime position in thymidylate kinase enzymatic pockets in molecular docking studies. The molecule 40 being most potent had shown a binding energy of -9.67 Kcal/mol, while docking against thymidylate kinase, which was compared with its in vitro MIC value (~8 μM). These findings suggest that 2-aminopyridine-3-carbonitrile and 2-amino-4H-pyran-3-carbonitrile derivatives are prospective lead molecules for the development of novel antitubercular drugs.
Exploration of Fulvic Acid as a Co-Former in Crystal Engineering Kattamanchi Gnananath, Kolli Prabhanjan Kumar, Yejella Rajendra Prasad, Kalakonda Sri Nataraj, Mohamad Taleuzzaman, et al. Separations, 2022 The aim of the project was to investigate Peat-derived Fulvic acid for its propensity to form co-crystals with quercetin and curcumin and characterize it by using different analytical techniques. The formation of co-crystals generally enhances water solubility and the overall bioavailability of molecules. Co-crystals were synthesized using a 1:1 stoichiometric ratio of fulvic acid with quercetin and curcumin, respectively, using solvent crystallization techniques taking tetrahydrofuran and water in a 1:1 v/v ratio. The co-crystals were characterized by spectroscopic methods, FTIR and Differential scanning calorimetry. Further confirmation was made by morphological studies using SEM. A structural analysis was also carried out, using 13C solid-state NMR analysis. The studies confirmed the formation of semi crystalline forms. Furthermore, the saturation solubility displayed the enhancement in solubility of up to 10, 5-folds for Quercetin and Curcumin, respectively. The in vitro dissolution results showed that T50% was achieved within 30 min for both the drugs. The literature supports that the nutraceutical co-crystals offer advantages, particularly in the improvement of biopharmaceutical properties and addressing the challenges of the lab and manufacturing scale process. Both the semi crystalline powders exhibited enhanced solubility and a better dissolution profile.
Synthesis, Anticancer and Antiviral Activity Studies of 1,3,4-Oxadiazoles: A Review K. DEVI, A. SRINIVASA RAO, Y. RAJENDRA PRASAD, K. RAJU, D. GEETA MOUNIKA Asian Journal of Chemistry, 2022 1,3,4-Oxadiazole is a five membered heterocyclic nucleus and a versatile lead structure, where its derivatives showed broad and potent biological functions especially as anticancer and antiviral agents which are associated with various mechanisms such as inhibition of different enzymes, kinases and growth factors. The present review summarizes various synthetic procedures and highlights the targeted inhibitory activities of 1,3,4-oxadiazoles as potential anticancer and antiviral agents along with their structure activity relationship. Molecular modeling and pharmacokinetic studies on 1,3,4-oxadiazoles proved a change in their polarity, flexibility and metabolic stability led to their improved biological activity potential. Among all the substituted 1,3,4-oxadiazoles, the mono- and 2,5-disubstituted derivatives showed considerable biological activities especially as anticancer and antiviral agents. Hence, scientists/researchers considered these as future lead molecules to treat cancer and viral infections along with other diseases. In future, the oxadiazole motif is likely to be incorporated in various other therapeutic molecules.
Design, synthesis, and antibacterial and antifungal activities of novel trifluoromethyl and trifluoromethoxy substituted chalcone derivatives Surendra Babu Lagu, Rajendra Prasad Yejella, Richie R. Bhandare, Afzal B. Shaik Pharmaceuticals, 2020 Despite the availability of many drugs to treat infectious diseases, the problems like narrow antimicrobial spectrum, drug resistance, hypersensitivities and systemic toxicities are hampering their clinical utility. Based on the above facts, in the present study, we designed, synthesized and evaluated the antibacterial and antifungal activity of novel fluorinated compounds comprising of chalcones bearing trifluoromethyl (A1–A10) and trifluoromethoxy (B1–B10) substituents. The compounds were characterized by spectroscopic techniques and evaluated for their antimicrobial activity against four pathogenic Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative (Escherichia coli and Bacillus subtilis) bacterial and fungal (Candida albicans and Aspergillus niger) strains. In this study, the compounds with trifluoromethoxy group were more effective than those with trifluoromethyl group. Among the 20 fluorinated chalcones, compound A3/B3 bearing an indole ring attached to the olefinic carbon have been proved to possess the most antimicrobial activity compared to the standard drugs without showing cytotoxicity on human normal liver cell line (L02). Further, the minimum inhibitory concentration (MIC) for A3/B3 was determined by serial tube dilution method and showed potential activity. These results would provide promising access to future study about the development of novel agents against bacterial and fungal infections.
Synthesis and in vitro studies of thiazolidine-4-carboxylic acid hydrazones as potential antitubercular agents Indian Journal of Chemistry Section B Organic and Medicinal Chemistry, 2018
Comparative in vitro antioxidant activities of ethanolic extract, ethyl acetate extract (EAE), and hexane extracts (HE) of Tecoma gaudichaudi flowers International Journal of Green Pharmacy, 2018
