Direct Enantiomeric Resolution of Betaxolol with Application to Analysis of Pharmaceutical Products

A high-performance liquid chromatographic (HPLC) method has been developed for the separation and determination of S- and R-enantiomers of betaxolol in tablets and ophthalmic preparations. Baseline resolution was achieved by using teicoplanin macrocyclic antibiotic chiral stationary phase (CSP) known as Chirobiotic T with fluorescence detection at excitation/emission wavelengths 275/305 nm. The polar ionic mobile phase (PIM) consists of methanol-glacial acetic acid-triethylamine, (100:0.020:0.025, v/v/v) has been used at a flow rate of 1.5 ml/min. All analytes with S-(–)-atenolol as internal standard were conducted at ambient temperature. The method is highly specific where another coformulated compounds did not interfere. The stability of betaxolol enantiomers under different degree of temperature also studied. The results showed that it is stable for at least 7 days at 70°C. The method validated for its linearity, accuracy, precision and robustness. Experimental design was used during validation to evaluate method robustness. Using the chromatographic conditions described, S- and R-betaxolol were well resolved with mean retention times of 11.3 and 12.6 min, respectively. Linear response (r > 0.997) was observed over the range of 10–500 ng/ml of betaxolol enantiomers, with detection limit of 5 ng/ml. The recoveries of S- and R-betaxolol from tablets and ophthalmic preparation ranged from 97.4 to 101.4% and 98.0 to 102.0%, respectively. The mean relative standard deviation (R.S.D.%) for both enantiomers were 1.1–1.4% and 1.3–1.7% in tablets and ophthalmic solution, respectively

A Practical Fast Acting Control Scheme For Fuzzy Logic-Based Voltage Stabilization Control

This paper presents a simplified control model for stabilizing a load voltage using a switched reactor in parallel with a fixed capacitor of static VAR compensator. Two IGBT’s are used to control the reactance of the switched reactor. A uniform pulse width modulation is used for controlling the two switches. The compensator has a simple control circuit and structure. A complete modeling and numerical simulation for the proposed systems is presented. A high speed Digital Signal Processor is used for implementing proportional-integral (PI) and fuzzy load voltage controllers. Experimental results indicate the superiority of fuzzy logic control over the conventional proportional-integral control method. Simulation results are reported and proved to be in good agreement with the relevant experimental results

Silica-Coated Magnetic Nanoparticles for Vancomycin Conjugation

Drug resistance is a global health challenge with thousands of deaths annually caused by bacterial multidrug resistance (MDR). Efforts to develop new antibacterial molecules do not meet the mounting needs imposed by the evolution of MDR. An alternative approach to overcome this challenge is developing targeted formulations that can enhance the therapeutic efficiency and limit side effects. In this aspect, vancomycin is a potent antibacterial agent that has inherent bacterial targeting properties by binding to the D-Ala-D-Ala moiety of the bacterial peptidoglycan. However, the use of vancomycin is associated with serious side effects that limit its clinical use. Herein, we report the development of vancomycin-conjugated magnetic nanoparticles using a simple conjugation method for targeted antibacterial activity. The nanoparticles were synthesized using a multistep process that starts by coating the nanoparticles with a silica layer, followed by binding an amide linker and then binding the vancomycin glycopeptide. The developed vancomycin-conjugated magnetic nanoparticles were observed to exhibit a spherical morphology and a particle size of 16.3 ± 2.6 nm, with a silica coating thickness of 5 nm and a total coating thickness of 8 nm. The vancomycin conjugation efficiency on the nanoparticles was measured spectrophotometrically to be 25.1%. Additionally, the developed formulation retained the magnetic activity of the nanoparticles, where it showed a saturation magnetization value of 51 emu/g, compared to 60 emu/g for bare magnetic nanoparticles. The in vitro cell biocompatibility demonstrated improved safety where vancomycin-conjugated nanoparticles showed IC50 of 183.43 μg/mL, compared to a much lower value of 54.11 μg/mL for free vancomycin. While the antibacterial studies showed a comparable activity of the developed formulation, the minimum inhibitory concentration was 25 μg/mL, compared to 20 μg/mL for free vancomycin. Accordingly, the reported formulation can be used as a platform for the targeted and efficient delivery of other drugs

Evaluation of some phenolic extracts against aphids (Aphis craccivora) Koch under laboratory conditions

Local farmers worldwide have complained in recent years that insect pests have become resistant to the majority of insecticides, owing to pesticide abuse. In addition, highly poisonous and harmful substances may cause health and environmental dangers. Friendly alternatives such as plant extracts are the main targets as substituents to synthetic pesticides. The present study aimed to extract total phenols from some plants and evaluate their efficacy on aphids, Aphis craccivora, under laboratory conditions. Four methanolic plant extracts from Punica granatum, Lantana camara, Portulaca oleracea and Ziziphus jujuba, containing phenolic components were evaluated against A. craccivora through: slide dipping, spraying, and leaf dipping techniques. Generally, positive relationships between the concentrations of the tested phenolic extracts and their mortality percentages were noticed in the case of slide dipping and spraying techniques. Conversely, no biological efficacy was found using the leaf dipping technique. The descending order of effectiveness of the tested extracts depending on their EC50 values was 0.017, 0.321, 1.142 and 16.114 ppm for Z. jujuba, P. oleraceae P. granatum and L. comara, respectively, in the case of the slide dipping technique. In contrast, P. granatum, L. camara, P. oleraceae and Z. jujuba had EC50 values of 0.0023, 0.017, 0.321 and 2.3409 ppm, respectively, in the case of the spraying technique. Additionally, a direct proportion was found between mortality percentages and treatment period for plant extracts under study with both techniques. After formulation and completion of additional essential field research, phenols isolated from the plants under study could be employed to combat A. craccivora

CHEMICAL PROFILE OF TWO JASMINUM SAMBAC L. (AIT) CULTIVARS CULTIVATED IN EGYPT–THEIR MEDIATED SILVER NANOPARTICLES SYNTHESIS AND SELECTIVE CYTOTOXICITY

Objective: Evaluation of two Jasminum sambac L. (Ait) cultivars; Arabian Nights (JSA) and Grand Duke of Tuscany (JSG) ethanolic leaves extracts as reducing agents for the green synthesis of silver nanoparticles (AgNPs) and evaluation of their cytotoxicity against MCF-7 breast cancer and 5637 bladder cancer cell lines and chemical profiling of the two cultivars. Methods: The synthesis of silver nanoparticles (AgNPs) by the two cultivars and characterization of AgNPs by ultraviolet (UV)–visible spectroscopy, Transmission electron microscopy (TEM) and Fourier Transform Infrared Spectroscopy (FTIR). Additionally, the use of The high-performance liquid chromatography coupled with photodiode array-mass-mass-spectroscopy (HPLC-PDA-MS/MS) for chemical profiling of both cultivars and evaluation of total leaves extracts and corresponding nanoparticles towards MCF-7 and 5637 cell lines compared to aneuploidy immortal keratinocyte (Ha Cat) normal cells by neutral cell assay. Results: The green synthesized AgNPs (of an average size range of 8.83 and 11.24 nm for JSA and JSG, respectively) exhibited cytotoxicity against MCF-7 and 5637 cell lines. The IC50 was determined for each total extract JSA (15.29±2.16 μg/ml) and JSG (20.28±1.20 μg/ml) and corresponding AgNPs 17.32±2.22 μg/ml and 6.32±1.01μg/ml for JSA and JSG, respectively. The IC50 of JSA and JSG against 5637 bladder cancer cell line were 13.76±1.11 μg/ml and 50.69±3.75 μg/ml, while the corresponding AgNPs showed IC50 of 5.54±0.88 μg/ml and 27.89±2.84 μg/ml, respectively. The HPLC-PDA-MS/MS allowed the identification of 59 compounds; 10 simple phenols, 17 flavonoids; quercetin and kaempferol glycosides, 2 lignans, and 30 secoiridoids; oleuropein, molihauside, and sambacoside. Conclusion: This study proved that JSA is an excellent source for the synthesis of AgNPs with optimum characters and enhanced activities toward MCF-7 and 5637 cell lines in correlation to identified compounds

FORMULATION AND ASSESSMENT OF A HERBAL HAIR CREAM AGAINST CERTAIN DERMATOPHYTES

Objective: Developing an herbal antifungal formulation containing eruca and garlic oils against highly resistant dermatophytes (Malassezia fufur AUMC No. 5173, Microsporum canis bodin AUMC No. 5490 and Trichophyton mentagrophytes AUMC No. 5501. 5501) and assessment of garlic oil thiosulfonates during the ex vivo percutaneous permeation through albino rat skin.Methods: Assay of antifungal activity was performed by filter paper disc method and agar well diffusion method. The components of volatile constituents and fixed oil of eruca seeds were studied using GC/MS. Thiosulfinates in garlic oil were analyzed by HPLC/UV. Both oils were incorporated into hair cream using span 60 and brij 58 at three different concentrations (2, 4 and 6% w/w) and alliin, was ex vivo evaluated using albino rat skin mounted on Franz diffusion cells.Results: The two oils have a synergistic effect on the first and additive effect on the second and the third fungi. The main constituents in eruca are 4-(methyl thio) butyl isothiocyanate (82%) for volatile constituents and erucic acid (40%) for the fixed one. The highest flux for alliin (0.337±0.0015 mg/cm2/hr) was obtained at a 4% surfactant concentration.Conclusion: Combination of oils has a high activity on the selected dermatophytes. Formulation of an herbal hair cream using span 60 and Brij 58 with a concentration 4% gives the highest permeation rate for alliin in garlic oil.Keywords: Eruca, Garlic, Dermatophytes, Quantitative determination and Ex-vivo permeatio

High-performance liquid chromatography and derivative spectrophotometry for simultaneous determination of pravastatin and fenofibrate in the dosage form

High performance liquid chromatography (HPLC) and second-order derivative spectrophotometry have been used for simultaneous determination of pravastatin (PS) and fenofibrate (FF) in pharmaceutical formulations. HPLC separation was performed on a phenyl HYPERSIL C18 column (125 mm 4.6 mm i.d., 5 m particle diameter) in the isocratic mode using a mobile phase acetonitrile/0.1 % diethyl amine (50:50, V/V, pH 4.5) pumped at a flow rate of 1.0 mL min–1. Measurement was made at 240 nm. Both drugs were well resolved on the stationary phase, with retention times of 2.15 and 5.79 min for PS and FF, respectively. Calibration curves were linear (R = 0.999 for PS and 0.996 for FF) in the concentration range of 5–50 and 20–200 µg mL–1 for PS and FF, respectively. Pravastatin and fenofibrate were quantitated in combined preparations also using the second-order derivative response at 237.6 and 295.1 nm for PS and FF, respectively. Calibration curves were linear, with the correlation coefficient R = 0.999 for pravastatin and fenofibrate, in the concentration range of 5–20 and 3–20 µg mL–1 for PS and FF, respectively. Both methods were fully validated and compared; the results confirmed that they were highly suitable for their intended purpose

X-ray crystal structure, NMR, DFT investigations, pharmaco-kinetic, and toxicity of sarcotrocheliol: A pyrane-based cemranoids of marine origin

69-80One of a recently discovered marine origin cembranoids has been studied experimentally and theoretically to obtain its thorough structural, electronic, spectroscopic, and biochemical activity. The exact molecular structure of sarcotrocheliol (C20H34O2) 1 has been determined for the first time using a single crystal X-ray diffraction analysis. Crystallography shows that the molecule is crystalline as an orthorhombic, space group of P212121, with a = 9.20(4) Å, b = 10.80(4) Å, c = 19.99(9) Å. 1H, 13C and DEPT-135 NMR measurements of sarcotrocheliol1have been measured in four different deuterated solvents: CDCl3, CD3CN, MeOH-d4 and DMSO-d6. Theoretical calculations have been performed to find the main structural and electronic properties of the compound and matched with the experimental properties. The density functional theory (DFT) method at B3LYP/6-311++G(d,p) level of theory has been used for all computed properties. Vibrational frequencies have been determined using DFT calculations and compared with the experimental values. Computed chemical shifts in the NMR have been determined by the GIAO method. The correlation coefficients between the calculated and experimental NMR chemical shifts have been found to be 0.92 and 0.998 for 1H and 13C NMR, respectively. Physicochemical parameters of the compound versus reference drugs have been done. The isolated compound meets the main criteria of the employed rules indicating a drug-like character. The molecular docking studies have been performed for the compound toward the breast and prostate cancers

The predictive and prognostic potential of plasma telomerase reverse transcriptase (TERT) RNA in rectal cancer patients

Background: Preoperative chemoradiotherapy (CRT) followed by surgery is the standard care for locally advanced rectal cancer, but tumour response to CRT and disease outcome are variable. The current study aimed to investigate the effectiveness of plasma telomerase reverse transcriptase (TERT) levels in predicting tumour response and clinical outcome. Methods: 176 rectal cancer patients were included. Plasma samples were collected at baseline (before CRT\ubcT0), 2 weeks after CRT was initiated (T1), post-CRT and before surgery (T2), and 4\u20138 months after surgery (T3) time points. Plasma TERT mRNA levels and total cell-free RNA were determined using real-time PCR. Results: Plasma levels of TERT were significantly lower at T2 (Po0.0001) in responders than in non-responders. Post-CRT TERT levels and the differences between pre- and post-CRT TERT levels independently predicted tumour response, and the prediction model had an area under curve of 0.80 (95% confidence interval (CI) 0.73\u20130.87). Multiple analysis demonstrated that patients with detectable TERT levels at T2 and T3 time points had a risk of disease progression 2.13 (95% CI 1.10\u20134.11)-fold and 4.55 (95% CI 1.48\u201313.95)-fold higher, respectively, than those with undetectable plasma TERT levels. Conclusions: Plasma TERT levels are independent markers of tumour response and are prognostic of disease progression in rectal cancer patients who undergo neoadjuvant therapy