Bioanalytical Method Development and Validation of Memantine in Human Plasma by High Performance Liquid Chromatography with Tandem Mass Spectrometry: Application to Bioequivalence Study

A simple, sensitive, and rapid HPLC-MS/MS method was developed and validated for quantitative estimation of memantine in human plasma. Chromatography was performed on Zorbax SB-C18 (4.6 × 75 mm, 3.5 μm) column. Memantine (ME) and internal standard Memantine-d6(MED6) were extracted by using liquid-liquid extraction and analyzed by LC-ESI-MS/MS using multiple-reaction monitoring (MRM) mode. The assay exhibited a linear dynamic range of 50.00–50000.00 pg/ml for ME in human plasma. This method demonstrated an intra- and interday precision within the range of 2.1–3.7 and 1.4–7.8%, respectively. Further intra- and interday accuracy was within the range of 95.6–99.8 and 95.7–99.1% correspondingly. The mean recovery of ME and MED6 was 86.07 ± 6.87 and 80.31 ± 5.70%, respectively. The described method was successfully employed in bioequivalence study of ME in Indian male healthy human volunteers under fasting conditions

Antimicrobial efficacy of n-[3- chloro-(substituted aryl)-4-oxoazetidin- 1-yl] pyridine-4- carboxamides against resistant bacterial strains obtained from clinical isolates

Abstract Background: The treatment of infectious diseases is still an important and challenging problem due to emerging infectious diseases and increasing number of multi-drug resistant microbial pathogens which cause a variety of illnesses ranging from hospital-acquired pneumonia, bloodstream infections, urinary tract infections from catheters, abdominal infections and even meningitis. Methods: The main objective of the present study was to evaluate the antimicrobial efficacy and β-lactamase inhibitory activity of the synthesized 2-azetidinones against resistant bacterial strains obtained from clinical isolates. Results: The tested 2-azetidinones exhibited antimicrobial efficacy comparable to the standard drugs Ampicillin and Griseofelvin. Among the tested compounds, N-[3-chloro-2-(2,5-dimethoxyphenyl)-4-oxoazetidin-1-yl]pyridine-4-carboxamide(5o) exhibited the highest activity with MIC of 6.25 µg/mL (Gram +ve and Gram –ve bacteria),1.56 µg/mL (A. niger) and 3.12 µg/mL(A. terrus and P. chrysogenum) respectively. Also all the screened compounds (5d, 5f, 5h,5j,5o) exhibited more pronounced activity (MIC: 125 µg/mL) against resistant K. pneumonia obtained from clinical isolates compared to standard antibiotic Amoxycillin. The compounds when tested as admixtures with the standard antibiotic amoxicillin (1:2) exhibited similar antibacterial spectra in comparison to the most widely employed clinical combination Augmentin. The 2-azetidinonescan prove to be a cheaper alternative with similar potential β-lactamase inhibitory activity thereby proving their utility and benefit towards the development of anti-infectives for the treatment of infections caused by drug resistant microorganisms

FORMULATION AND EVALUATION OF TROPICAMIDE IN-SITU GELS LOADED SOLID LIPID NANOPARTICLES FOR OCULAR DRUG DELIVERY

The aim of present work Formulation and Evaluation of Tropicamide In-situ Gels loaded Solid Lipid Nanoparticles for Ocular Drug Delivery. The surface morphological of SLN was carried out by TEM. The Tropicamide loaded solid lipid nanoparticles was measured the average particle size was ranges from 182.1+3.12nm to 390.1±2.10 nm. The zeta potential ranges from -0.17±1.4 mV to -3.80±1.5 mV. The entrapment efficiency 66.2 % to 89.2 %. Drug content was ranges from 0.112mg/ml to 0.502 mg/ml. The percentage yield ranges from was ranges from 0.112mg/ml to 0.502 mg/ml. The polydispersity index ranged from 1.011±0.15 to 1.327±0.13. These SLN enriched in Chitosan gels the pH of the formulations range from 6.8 to 6.9. The gelling strength ranged from 129 sec to 152 sec. The bioadhesive force was ranges from 10.21 ±1.15 dynes/cm2 to 15.23 ± 1.22 dynes/cm2. The viscosity was ranges from 2212 ± 1.14 cps to 2420± 1.19 cps. The spreadability coefficient was ranges from 11.2 ± 1.10 gms/sec to 13.3 ± 1.21 gms/sec. The in-vitro diffusion release studies carried out at 12 hrs TSLNGF19 shows the 79.2 ± 0.32. The ex vivo permeation studies for optimized formulation the increased drug permeation and corneal accumulation. In vitro corneal permeation profile of tropicamide loaded SLN from the chitosan gels and commercial eye drop solution (Tropicacyl) across the isolated porcine cornea. The ocular tolerance studies performed with HETCAM assay, corneal hydration study, histopathological studies. The stability studies of chitosan gels for long-term stability as per ICH guidelines (25°C ± 2°C / 60% RH ± 5% RH) &accelerated stability as per ICH guidelines (40°C ± 2°C / 75% RH ± 5% RH) there is no changes in gelling strength, bioadhesive force, viscosity, spreadability coefficient in optimized formulation. Keywords: Chitosan, Corneal hydration studies, ex vivo permeation, in vitro diffusion studies, Solid Lipid Nanoparticle

A NOVEL APPROACHES ON OCULAR DRUG DELIVERY SYSTEM

The purpose of this review is giving a current update of the knowledge in this field of ocular drug delivery. The ocular drug delivery has been a major challenge to drug delivery scientists mainly due to its unique anatomy and physiology. One of the major problems encountered by the conventional ocular dosage forms include the rapid precorneal drug loss due to its nasolacrimal drainage, tear turnover and drug dilution resulting in poor bioavailability. These efforts lead to development of novel drug delivery dosage forms such as nanoparticles, liposome, ocuserts, and mucoadhesive formulations. Controlled drug delivery systems offer many advantages over conventional dosage forms in terms of improving drug bioavailability, reducing toxicity and decreasing dosage frequency. Designing noninvasive sustained drug delivery systems and exploring the feasibility of topical application to deliver drugs to the posterior segment may drastically improve drug delivery in the years to come. Keywords: Ocular drug delivery, Eye, Conventional drug delivery, novel dosage forms, approaches.Â

Carboxymethylcellulose hydrogels support central nervous system-derived tumor-cell chemotactic migration: comparison with conventional extracellular matrix macromolecules

The local microenvironment plays an important role in maintaining the dynamics of the extracellular matrix and the cell-extracellular matrix relationship. The extracellular matrix is a complex network of macromolecules with distinct mechanical and biochemical characteristics. Disruptions in extracellular matrix homeostasis are associated with the onset of cancer. The extracellular matrix becomes highly disorganized, and the cell-matrix relationship changes, resulting in altered cell-signaling processes and metastasis. Medulloblastoma is one of the most common malignant pediatric brain tumors in the United States. In order to gain a better understanding of the interplay between cell-extracellular matrix interactions and cell-migratory responses in tumors, eight different matrix macromolecule formulations were investigated using a medulloblastoma-derived cell line: poly-D-lysine, matrigel, laminin, collagen 1, fibronectin, a 10% blend of laminin-collagen 1, a 20% blend of laminin-collagen 1, and a cellulose-derived hydrogel, carboxymethylcellulose. Over time, the average changes in cell morphology were quantified in 2D and 3D, as was migration in the presence and absence of the chemoattractant, epidermal growth factor. Data revealed that carboxymethylcellulose allowed for a cell-extracellular matrix relationship typically believed to be present in tumors, with cells exhibiting a rounded, amoeboid morphology consistent with chemotactic migration, while the other matrices promoted an elongated cell shape as well as both haptotactic and chemotactic motile processes. Therefore, carboxymethylcellulose hydrogels may serve as effective platforms for investigating central nervous system-derived tumor-cell migration in response to soluble factor

Structural, electronic, magnetic, and thermal properties of single-crystalline UNi0.5Sb2

We studied the properties of the antiferromagnetic (AFM) UNi0.5Sb2 (TN \approx 161 K) compound in Sb-flux grown single crystals by means of measurements of neutron diffraction, magnetic susceptibility ({\chi}), specific heat (Cp), thermopower (S), thermal conductivity ({\kappa}), linear thermal expansion ({\Delta}L/L), and electrical resistivity ({\rho}) under hydrostatic pressures (P) up to 22 kbar. The neutron diffraction measurements revealed that the compound crystallizes in the tetragonal P42/nmc structure, and the value of the U-moments yielded by the histograms at 25 K is \approx 1.85 \pm 0.12 {\mu}B/U-ion. In addition to the features in the bulk properties observed at TN, two other hysteretic features centered near 40 and 85 K were observed in the measurements of {\chi}, S, {\rho}, and {\Delta}L/L. Hydrostatic pressure was found to raise TN at the rate of \approx 0.76 K/kbar, while suppressing the two low temperature features. These features are discussed in the context of Fermi surface and hybridization effects.Comment: 17 pages, 8 figure

Local algorithms : Self-stabilization on speed

Non peer reviewe