Application of Elements of Quality by Design to Development and Optimization of HPLC Method for Fingolimod

Purpose: A HPLC method for Fingolimod was developed using a Quality by Design concept. QbD has gained importance in recent times due to regulatory requirements. Actual study was started after determination of target profile and qualification of instrument. Methods: Separation was carried on a Grace C-8 column (4.6 x 250 mm, 5-μm particle size).The composition of mobile phase was methanol and 20 mM ammonium formate buffer of pH5.8 in gradient mode HPLC method development is affected by critical factors like pH, flow rate and mobile phase composition. Results: To study the effects of these three factors on USP tailing, Box Behnken optimization model was applied. Desirability of the model was set at Tailing less than 1.2.Analysis of results was done using surface diagrams. Verification of Software generated results was done by taking six replicates of the run. Thus developed and optimised method was Finally validated as per ICH guideline. Conclusion: A Quality by Design approach has been successfully utilised in method development of the Fingolimod in bulk. All key aspect of QbD were tried to be implemented in said study. Systematic approach was utilized for method development which includes beginning with determination of target profile characteristics, instrument qualification, risk assessment, design of experiment and validation. Three factors i.e. Ph, flow rate and methanol concentration were analysed for their effect on USP tailing as a responce. Interaction and quadratic effect of the factors were studied with least possible runs by using Box Behnken model. Response surface diagrams and contour plots were studied for coming to conclusion which factors are affecting response and their limits were recorded. Optimum run condition was obtained; Replicates of run having optimized condition were taken to confirm the predicted response with actual response

Evaluation of rheological properties and swelling behaviour of sonicated Scleroglucan samples

Scleroglucan is a natural polysaccharide that has been proposed for various applications. However there is no investigation on its property variations when the molecular weight of this polymer is reduced. Scleroglucan was sonicated at two different polymer concentrations for different periods of time and the effect of sonication was investigated with respect to molecular weight variations and rheological properties. Molar mass, estimated by viscometric measurements, was drastically reduced already after a sonication for a few min. Sonicated samples were used for the preparation of gels in the presence of borate ions. The effect of borax on the new samples was investigated by recording the mechanical spectra and the flow curves. A comparison with the system prepared with the dialysed polymer was also carried out. The anisotropic elongation, observed with tablets of scleroglucan and borax, was remarkably reduced when the sonicated samples were used for the preparation of the gels

Green Synthesis of ZnO Nanostructures Using Pyrus pyrifolia: Antimicrobial, Photocatalytic and Dielectric Properties

In this study, zinc oxide nanostructures (ZnO NS) were synthesized using Pyrus pyrifolia fruit extract. Biophysical characterization results confirmed that the synthesized materials are crystalline wurtzite ZnO structures. Field emission scanning electron microscopy (FESEM) revealed that the ZnO NS are cubical, and the sizes range 20–80 nm. Transmission electron microscopy (TEM) and XRD results revealed a crystal lattice spacing of 0.23 nm and (101) the crystalline plane on ZnO NS. UV-Visible spectrophotometer results showed an absorbance peak at 373 nm. The ZnO NS demonstrated significant antibacterial activity analyzed by metabolic activity analysis and disc diffusion assay against Escherichia coli and Staphylococcus aureus. FESEM analysis confirmed the bacterial membrane disruption and the release of cytoplasmic contents was studied by electron microscopy analysis. Further, ZnO NS achieved good photocatalytic activity of decolorizing 88% of methylene blue (MB) in 60 min. The dielectric constant and loss of ZnO were found to be 3.19 and 2.80 at 1 kHz, respectively. The research findings from this study could offer new insights for developing potential antibacterial and photocatalytic materials

Green Synthesis of ZnO Nanostructures Using <i>Pyrus pyrifolia</i>: Antimicrobial, Photocatalytic and Dielectric Properties

In this study, zinc oxide nanostructures (ZnO NS) were synthesized using Pyrus pyrifolia fruit extract. Biophysical characterization results confirmed that the synthesized materials are crystalline wurtzite ZnO structures. Field emission scanning electron microscopy (FESEM) revealed that the ZnO NS are cubical, and the sizes range 20–80 nm. Transmission electron microscopy (TEM) and XRD results revealed a crystal lattice spacing of 0.23 nm and (101) the crystalline plane on ZnO NS. UV-Visible spectrophotometer results showed an absorbance peak at 373 nm. The ZnO NS demonstrated significant antibacterial activity analyzed by metabolic activity analysis and disc diffusion assay against Escherichia coli and Staphylococcus aureus. FESEM analysis confirmed the bacterial membrane disruption and the release of cytoplasmic contents was studied by electron microscopy analysis. Further, ZnO NS achieved good photocatalytic activity of decolorizing 88% of methylene blue (MB) in 60 min. The dielectric constant and loss of ZnO were found to be 3.19 and 2.80 at 1 kHz, respectively. The research findings from this study could offer new insights for developing potential antibacterial and photocatalytic materials

Oxalic acid catalyzed solvent-free synthesis of <img src='/image/spc_char/alpha.gif' border=0>-amidoalkyl-β-naphthols

71-73An efficient one-pot synthesis of -amidoalkyl-β-naphthols is described. This involves the three-component reaction of β-naphthol, aromatic aldehydes and amide or urea in the presence of a catalytic amount of oxalic acid under solvent-free condition

Preparation and characterization of Meta-bromo-thiolactone calcium alginate nanoparticles

Recently, the focus has been shifting toward Quorum sensing inhibitors which reduce Pseudomonas aeruginosa virulence factors, alleviating infections. In this work, me-ta-bromo-thiolactone (mBTL), a potent quorum and virulence inhibitor for the Pseudomonas aeruginosa strains, were formulated in calcium alginate nanoparticles (CANPs). Alginate is used as nutrients and as backbone virulence aspect for Pseudomonas and therefore was chosen. mBTL-loaded-CANPs were characterized for particle size, polydispersity index, zeta potential, morphology visualized by Transmission Electron Microscopy (TEM) and drug release profile. Chemical and physical analysis of formulated mBTL-loaded-CANPs were evaluated using Fourier transform infrared Spectroscopy (FTIR) and differential scanning calorimetry (DSC) and Physical stability of mBTL-loaded-CANPs assessed at various temperature 25 ± 1 °C, 4 ± 0.5 °C and −30° ± 1 °C over a period of 4 and 9 months. Synthesized CANPs showed nano-size particles ranging from 140 to 200 nm with spherical particles for plain CANPS and irregular shape for mBTL-loaded-CANPs with a sustainable release profile over 48hrs. FTIR showed stable structure of loaded-mBTL and DSC displayed no interaction between mBTL and polymer. State of released mBTL from CANPs kept at 25 °C, 4 °C and −30 °C over 4 and 9 months showed stable formula at room temperature which kept as a goal of nanoparticles storage. The findings of this study revealed successful preparation of mBTL-loaded-CANPs

Anxiolytic-<i>like</i> Effects by <i>trans</i>-Ferulic Acid Possibly Occur through GABAergic Interaction Pathways

Numerous previous studies reported that ferulic acid exerts anxiolytic activity. However, the mechanisms have yet to be elucidated. The current study aimed to investigate the anxiolytic effect of trans-ferulic acid (TFA), a stereoisomer of ferulic acid, and evaluated its underlying mechanism using in vivo and computational studies. For this, different experimental doses of TFA (25, 50, and 75 mg/kg) were administered orally to Swiss albino mice, and various behavioral methods of open field, hole board, swing box, and light–dark tests were carried out. Diazepam (DZP), a positive allosteric modulator of the GABAA receptor, was employed as a positive control at a dose of 2 mg/kg, and distilled water served as a vehicle. Additionally, molecular docking was performed to estimate the binding affinities of the TFA and DZP toward the GABAA receptor subunits of α2 and α3, which are associated with the anxiolytic effect; visualizations of the ligand-receptor interaction were carried out using various computational tools. Our findings indicate that TFA dose-dependently reduces the locomotor activity of the animals in comparison with the controls, calming their behaviors. In addition, TFA exerted the highest binding affinity (−5.8 kcal/mol) to the α2 subunit of the GABAA receptor by forming several hydrogen and hydrophobic bonds. Taken together, our findings suggest that TFA exerts a similar effect to DZP, and the compound exerts moderate anxiolytic activity through the GABAergic interaction pathway. We suggest further clinical studies to develop TFA as a reliable anxiolytic agent