Marianne Nebsen

Removal of cationic and anionic dyes from aqueous solution with magnetite/pectin and magnetite/silica/pectin hybrid nanocomposites: kinetic, isotherm and mechanism analysis

Novel adsorbents, magnetite nanoparticles modified with pectin shell and silica/pectin double shell, were fabricated and tested for single dye and dye mixture adsorption from water samples. Cationic dyes methylene blue (MB) and crystal violet (CV) and anionic dyes methyl orange (MO) and Eriochrome black T (EBT) were employed to assess dye removal efficiency. The influence of pH, amount of adsorbent, initial dye concentration and contact time was investigated. Results indicated that the optimum pH for removing cationic dyes was 8.0 and 2.0 for anionic dyes. The kinetic studies showed rapid sorption dynamics following a second-order kinetic model. Dye adsorption equilibrium data were fitted well to the Sips isotherm for cationic and anionic dyes. The maximum monolayer capacity, (qmax) for MB, CV, EBT and MO was calculated from Sips as 197.18, 180.29, 65.35 and 26.75 mg g−1 respectively for magnetite/silica/pectin NPs and 168.72, 140.49, 72.35 and 27.22 mg g−1 respectively for magnetite/pectin nanoparticles. For dye mixture adsorption, a new HPLC assay was proposed for quantitation of dyes in treated samples. The results came in accordance with that of single dye adsorption where the magnetite/pectin NPs showed preferred adsorption to anionic dyes while the magnetite/silica/pectin NPs had more affinity to cationic dyes. Thus, our proposed NPs can be used as cheap and efficient adsorbents for removal of cationic and anionic dyes from aqueous solutions.

Comparative study of 2-hydroxy propyl beta cyclodextrin and calixarene as ionophores in potentiometric ion-selective electrodes for neostigmine bromide

Three novel neostigmine bromide (NEO) selective electrodes were investigated with 2-nitrophenyl octyl ether as a plasticiser in a polymeric matrix of polyvinyl chloride (PVC). Sensor 1 was fabricated using tetrakis(4-chlorophenyl)borate (TpClPB) as an anionic exchanger without incorporation of an ionophore. Sensor 2 used 2-hydroxy propyl β-cyclodextrin as an ionophore while sensor 3 was constructed using 4-sulfocalix-8-arene as an ionophore. Linear responses of NEO within the concentration ranges of 10(-5) to 10(-2), 10(-6) to 10(-2) and 10(-7) to 10(-2) mol L(-1) were obtained using sensors 1, 2 and 3, respectively. Nernstian slopes of 51.6 ± 0.8, 52.9 ± 0.6 and 58.6 ± 0.4 mV/decade over the pH range of 4-9 were observed. The selectivity coefficients of the developed sensors indicated excellent selectivity for NEO. The utility of 2-hydroxy propyl β-cyclodextrin and 4-sulfocalix[8]arene as ionophores had a significant influence on increasing the membrane sensitivity and selectivity of sensors 2 and 3 compared to sensor 1. The proposed sensors displayed useful analytical characteristics for the determination of NEO in bulk powder, different pharmaceutical formulations, and biological fluids (plasma and cerebrospinal fluid (CSF)) and in the presence of its degradation product (3-hydroxyphenyltrimethyl ammonium bromide) and thus could be used for stability-indicating methods.

Stability-indicating spectrophotometric and spectrodensitometric methods for the determination of diacerein in the presence of its degradation product.

Three sensitive, selective, and precise stability-indicating methods for the determination of the novel osteoarthritis drug, diacerein (DIA) in the presence of its alkaline degradation product (active metabolite, rhein) and in pharmaceutical formulation were developed and validated. The first method is a first derivative (D(1) ) spectrophotometric one, which allows the determination of DIA in the presence of its degradate at 322 nm (corresponding to zero crossing of the degradate) over a concentration range of 4-40 µg/mL with mean percentage recovery 100.21 ± 0.833. The second method is the first derivative of the ratio spectra (DD(1) ) by measuring the peak amplitude at 352 nm over the same concentration range as (D(1) ) spectrophotometric method, with mean percentage recovery 100.09 ± 0.912. The third method is a TLC-densitometric one, where DIA was separated from its degradate on silica gel plates using ethyl acetate:methanol:chloroform (8:1.5:0.5 v:v:v) as a developing system. This method depends on quantitative densitometric evaluation of thin layer chromatogram of DIA at 340 nm over a concentration range of 1-10 µg/spot, with mean percentage recovery 100.24 ± 1.412. The selectivity of the proposed methods was tested using laboratory-prepared mixtures. The proposed methods have been successfully applied to the analysis of DIA in pharmaceutical dosage forms without interference from other dosage form additives and the results were statistically compared with reference method.

In vitro stabilization and in vivo improvement of ocular pharmacokinetics of the multi-therapeutic agent baicalin: Delineating the most suitable vesicular systems

Baicalin is a multi-purpose flavonoid used in the treatment of different ocular diseases. Owing to its poor stability in basic pH and its poor solubility, a suitable carrier system is needed to enhance its ocular therapeutic potential. Therefore, the objective of this work was to prepare and contrast different baicalin vesicular systems; namely liposomes, penetration enhancer vesicles PEVs and transfersomes. Results revealed that baicalin vesicles exhibited suitable particle size and zeta potential, high entrapment efficiency and controlled release. Depending on the vesicular composition, selected formulations were able to resist physical changes of particle size, zeta potential, entrapment efficiency and in vitro release after storage for 3 months, while retarding the degradation of baicalin. Selected vesicular formulations displayed equivalent or superior antioxidant potential compared to baicalin solution, with absolute superiority over ascorbic acid reference, while demonstrating sterilization endurance and safety on ocular tissues. Pharmacokinetic studies revealed that transfersomes displayed the fastest onset of action, while liposomes displayed the highest extent of absorption as concluded from the Tmax, Cmax, and AUC0-∞ values with 4-5 folds increase in bioavailability compared to baicalin control solution. This delineates baicalin vesicular systems as a promising platform for treatment of ocular diseases such as inflammation, cataract and diabetic retinopathy.

Gallic acid magnetic nanoparticles for photocatalytic degradation of meloxicam: synthesis, characterization and application to pharmaceutical wastewater treatment

Environmentally friendly gallic acid coated magnetic nanoparticles (GA-MNP) have been synthesized and evaluated as a novel photocatalyst for degradation of meloxicam; a commonly prescribed nonsteroidal anti-inflammatory drug. The synthesized GA-MNP were characterized using transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy and dynamic light scattering. Results showed the formation of core–shell MNP with a mean hydrodynamic diameter of 160.55 ± 5.02 nm and zeta potential of −42.4 ± 1.6 mV. A validated RP-HPLC stability-indicating assay was developed for monitoring of meloxicam concentration in the presence of its degradation products and for determination of the kinetics of degradation. Full factorial design (24) was employed in order to investigate the effects of pH, irradiation time, GA-MNP loading and initial meloxicam concentration on the efficiency of the process. The irradiation time was found to be the most significant parameter followed by initial meloxicam concentration and GA-MNP loading, respectively. At the optimized conditions, increasing GA-MNP loading to 5.00 mg mL−1 demonstrated superior photocatalytic activity when compared to bare MNP and TiO2NP. Meloxicam degradation was found to follow pseudo first order rate kinetics with Kobs and t0.5 of −0.0029 min−1 and 239 min, respectively. The protocol was successfully applied for treatment of incurred water samples collected during various cleaning validation cycles. A percentage degradation of 89.10 ± 0.13% was achieved upon irradiation of samples containing 64.57 ± 0.09 µg mL−1 with UV light (1012 µW cm−2, 8 h) in the presence of 5 mg mL−1 GA-MNP at pH 9.0 ± 0.05. It could be suggested that treatment of wastewaters collected during the cleaning validation of each pharmaceutical product, before pooling into the general waste pool, should improve the efficiency and economics of pharmaceutical wastewater treatment.

Magnetic molecularly imprinted polymer nanoparticles for simultaneous extraction and determination of 6-mercaptopurine and its active metabolite thioguanine in human plasma

Cytotoxic drugs used in cancer chemotherapy require the continuous monitoring of their plasma concentration levels for dose adjustment purposes. Such condition necessitates the presence of a sensitive technique for accurate extraction and determination of these drugs together with their active metabolites. In this study a novel solid phase extraction technique using magnetic molecularly imprinted nanoparticles (MMI-SPE) is combined with liquid chromatography tandem mass spectrometry (LC-MS/MS) to extract and determine the anti-leukemic agent; 6-mercaptopurine (6-MP) and its active metabolite thioguanine (TG) in human plasma. The magnetic molecularly imprinted nanoparticles (Fe3O4@MIP NPs) were synthesized via precipitation polymerization technique and were characterized using different characterization methods A computational approach was adopted to help in the choice of the monomer used in the fabrication process. The Fe3O4@MIPs NPs possessed a highly improved imprinting efficiency, fast adsorption kinetics following 2nd order kinetics and good adsorption capacity of 1.0 mg/g. The presented MMI-SPE provided the optimum approach in comparison to other reported ones to achieve good extraction recovery and matrix effect of trace levels of 6-MP and TG from plasma. Chromatographic separation was carried out using a validated LC-MS/MS assay and recovery, matrix effect and process efficiency were evaluated. Recovery of 6-MP and TG was in the range of 85.94-103.03%, while, matrix effect showed a mean percentage recovery of 85.94-97.62% and process efficiency of 85.54-96.18%. The proposed extraction technique is simple, effective and can be applicable to the extraction and analysis of other pharmaceutical compounds in complex matrices for therapeutic drug monitoring applications.

Computer-aided design of magnetic molecularly imprinted polymer nanoparticles for solid-phase extraction and determination of levetiracetam in human plasma

Analytical methods should be accurate and specific to measure plasma drug concentration. Nevertheless, current sample preparation techniques suffer from limitations, including matrix interference and intensive sample preparation. In this study, a novel technique was proposed for the synthesis of a molecularly imprinted polymer (MIP) on magnetic Fe3O4 nanoparticles (NPs) with uniform core–shell structure. The Fe3O4@MIPs NPs were then applied to separate and enrich an antiepileptic drug, levetiracetam, from human plasma. A computational approach was developed to screen the functional monomers and polymerization solvents to provide a suitable design for the synthesized MIP. Different analysis techniques and re-binding experiments were performed to characterize the Fe3O4@MIP NPs, as well as to identify optimal conditions for the extraction process. Adsorption isotherms were best fitted to the Langmuir model and adsorption kinetics were modeled with pseudo-second-order kinetics. The Fe3O4@MIP NPs showed reasonable adsorption capacity and improved imprinting efficiency. A validated colorimetric assay was introduced as a comparable method to a validated HPLC assay for the quantitation of levetiracetam in plasma in the range of 10–80 μg mL−1 after extraction. The results from the HPLC and colorimetric assays showed good precision (between 1.08% and 9.87%) and recoveries (between 94% and 106%) using the Fe3O4@MIP NPs. The limit of detection and limit of quantification were estimated to be 2.58 μg mL−1 and 7.81 μg mL−1, respectively for HPLC assay and 2.32 μg mL−1 and 7.02 μg mL−1, respectively for colorimetric assay. It is believed that synthesized Fe3O4@MIP NPs as a sample clean-up technique combined with the proposed assays can be used for determination of levetiracetam in plasma.