ONCE DAILY IMMEDIATE-AND EXTENDED-RELEASE BILAYER TABLETS OF ETORICOXIB: A STUDY ON THE RELEASE KINETICS

Objective: In the present work, the main objective was to develop bilayer extended release matrix tablets of etoricoxib by providing a loading dose followed by maintenance dose that expected to improve the therapeutic efficacy of the medication with less toxic effect. Methods: Bilayer tablets of etoricoxib was developed successfully with the meticulous proportion of release controlling Hydroxy propyl methyl cellulose K100 (HPMC K100) and lactose. The tablets were prepared by wet granulation technique. Granules for immediate layer and extended layer for different formulations were prepared separately. The formulations were developed and evaluations were performed to examine the parameters that affect the in vitro performance of the tablets. The drug-excipient compatibility was ensured by Fourier transform infrared spectroscopy (FTIR) study. Results: The values of physical parameters of all formulations were found within appreciable limit. Formulation containing HPMC K 100 and lactose in the proportion of 2:1 in the extended release layer was able to release 26.22% of drug in 15 min and shown a steady release of drug for an extended period of 12 h. The dissolution data was put in Korsemeyer–Peppas model in order to find out n value, which describes the drug release mechanism. The n-value of different formulations were found to be variable. The Fourier transform infrared spectroscopy (FTIR) study revealed absence of any other new peaks and also no differences in the positions of the absorption bands in the bilayer tablet F8 that indicate the lack of significant interactions between etoricoxib and other excipients. Conclusion: It had been concluded that once daily immediate-and extended release bilayer tablet of etoricoxib can be formulated with profound physical characteristics and dissolution properties. This resulted in reducing the daily dose and thus minimise the cardiovascular toxicity of etoricoxib

Development of experiments on vacuum technology

Improvements in vacuum science and technology have triggered its application to wide areas of knowledge and it now plays an important role in many different industrial and research environments. The increasing use of elaborate and well designed vacuum systems leads to the need for well-trained staff and engineers in this area. The education and training of researchers and technicians by actual practice in laboratories has importance and significance in a field like vacuum science and technology. This is of particular importance for undergraduate and graduate student education, given the limited time available for teaching those curricula. It is very important for students’ education and training that direct quantitative measurements can be obtained during the experimental work, rather than just the simple operation of vacuum systems and qualitative analysis. Simple experiments, allowing students to perform direct measurements of the characteristics of different vacuum components and material properties, are thus important. We will describe simple experiments intended for didactic laboratory vacuum classes of undergraduate courses, where actual measurements are performed and compared with the values tabulated. These experiments are intended for five to six times 4-h laboratory classes of an introductory vacuum course for undergraduate students majoring in Physics, Physics Engineering and Material Sciences. Small high vacuum systems are used with a rough vacuum gauge at both the high-vacuum chamber and mechanical pump inlet. This allows the monitoring of the pressure in the vacuum chamber during the roughing procedure and after the high-vacuum valve is closed. Helium leak detectors have become common in both research and industrial environments. They have changed from luxury equipment, requiring expert handling, to economic, reliable and powerful monitoring instruments, which are relatively easy to use. Therefore, it is important to include these systems in the experimental training of students. A simple experiment, using a He leak detector to measure the helium permeability of different materials, is presented

Solubility and Dissolution Enhancement of Etoricoxib by Solid Dispersion Technique Using Sugar Carriers

The aim of the present study was to improve solubility and dissolution of the poorly aqueous soluble drug, etoricoxib by solvent evaporation technique using various sugar carriers, such as lactose, sucrose, and mannitol. Etoricoxib solid dispersions and their respective physical mixtures using lactose, sucrose, and mannitol were prepared in different ratios by solvent evaporation technique. The percent yield, drug content, saturation solubility, and in vitro dissolution of etoricoxib solid dispersions and physical mixtures were analyzed. Etoricoxib solid dispersions were characterized by FTIR spectroscopy, XRD, and DSC analysis. The FTIR spectroscopic analysis revealed the possibility of intermolecular hydrogen bonding in various solid dispersions. The XRD and DSC studies indicated the transformation of crystalline etoricoxib (in pure drug) to amorphous etoricoxib (in solid dispersions) by the solid dispersion technology. Both the aqueous solubility and dissolution of etoricoxib were observed in all etoricoxib solid dispersions as compared with pure etoricoxib and their physical mixtures. The in vitro dissolution studies exhibited improved dissolution in case of solid dispersion using lactose than the solid dispersions using both sucrose and mannitol. The in vitro dissolution of etoricoxib from these solid dispersions followed Hixson-Crowell model

The J-UNIO protocol for automated protein structure determination by NMR in solution

The J-UNIO (JCSG protocol using the software UNIO) procedure for automated protein structure determination by NMR in solution is introduced. In the present implementation, J-UNIO makes use of APSY-NMR spectroscopy, 3D heteronuclear-resolved [1H,1H]-NOESY experiments, and the software UNIO. Applications with proteins from the JCSG target list with sizes up to 150 residues showed that the procedure is highly robust and efficient. In all instances the correct polypeptide fold was obtained in the first round of automated data analysis and structure calculation. After interactive validation of the data obtained from the automated routine, the quality of the final structures was comparable to results from interactive structure determination. Special advantages are that the NMR data have been recorded with 6-10days of instrument time per protein, that there is only a single step of chemical shift adjustments to relate the backbone signals in the APSY-NMR spectra with the corresponding backbone signals in the NOESY spectra, and that the NOE-based amino acid side chain chemical shift assignments are automatically focused on those residues that are heavily weighted in the structure calculation. The individual working steps of J-UNIO are illustrated with the structure determination of the protein YP_926445.1 from Shewanella amazonensis, and the results obtained with 17 JCSG targets are critically evaluate

NMR structure of the protein NP_247299.1: comparison with the crystal structure

Comparison of the NMR and crystal structures of a protein determined using largely automated methods has enabled the interpretation of local differences in the highly similar structures. These differences are found in segments of higher B values in the crystal and correlate with dynamic processes on the NMR chemical shift timescale observed in solution

Comparison of NMR and crystal structures highlights conformational isomerism in protein active sites

Tools for systematic comparisons of NMR and crystal structures developed by the JCSG were applied to two proteins with known functions: the T. maritima anti-σ factor antagonist TM1081 and the mouse γ-glutamylamine cyclotransferase A2LD1 (gi:13879369). In an attempt to exploit the complementarity of crystal and NMR data, the combined use of the two structure-determination techniques was explored for the initial steps in the challenge of searching proteins of unknown functions for putative active sites

Comparison of NMR and crystal structures for the proteins TM1112 and TM1367

NMR structures of the proteins TM1112 and TM1367 solved by the JCSG in solution at 298 K could be superimposed with the corresponding crystal structures at 100 K with r.m.s.d. values of <1.0 Å for the backbone heavy atoms. For both proteins the structural differences between multiple molecules in the asymmetric unit of the crystals correlated with structural variations within the bundles of conformers used to represent the NMR solution structures. A recently introduced JCSG NMR structure-determination protocol, which makes use of the software package UNIO for extensive automation, was further evaluated by comparison of the TM1112 structure obtained using these automated methods with another NMR structure that was independently solved in another PSI center, where a largely interactive approach was applied

Dynamics and Control of an Energy-Efficient, Power-Regenerative, Hydrostatic Wind Turbine Dynamometer

Dynamometers are used to evaluate the real-world performances of drivetrains in various loading conditions. Due to its superior power density, high bandwidth, and design flexibility, a hydrostatic power-regenerative dynamometer is an ideal candidate for hydrostatic wind turbine transmission testing. A dynamometer can emulate the wind turbine rotor dynamics and allow the investigation of the performance of a unique hydrostatic drivetrain without actually building the physical system. The proposed dynamometer is an energy-efficient system with counter-intuitive control challenges. This paper presents the dynamics, control synthesis, and experimental validation of a power-regenerative hydrostatic dynamometer. A fourth-order non-linear model with three inputs was formulated for the dynamometer. The strength of input&ndash;output couplings was identified, and two different decoupling controllers were designed and implemented. During wind turbine testing, the synchronous generator turns at a constant speed and the system model is linear. A steady-state decoupling controller was developed for independent control of the drive and transmission. The implemented decoupling controller demonstrated a negligible change in rotor speed for a 40 bar step increase in pressure, but a 20 bar pressure spike for a 4 rpm step change in rotor speed. However, during starting and stopping, the synchronous generator speed is not constant, and the system model is nonlinear. Therefore, a steady-state decoupling controller will not work. Thus, a decentralized controller with feed-forward control and gain scheduling was designed and implemented. A reference command was designed to avoid cavitation, pressure spikes, and power flow reversal during start-up. The experimental results show precise tracking in steady-state and transient operations. The decentralized controller demonstrated a negligible change in rotor speed for a 40 bar step increase in pressure but a 100 bar pressure spike for a 4 rpm step increase in rotor speed. The pressure spike was reduced by 80 bar with the implementation of feed-forward gain. The proposed electro-hydro-mechanical system requires less power and has the potential to reduce energy expenditure by 50%

Experimental Validation of a Hydrostatic Transmission for Community Wind Turbines

Hydrostatic transmissions are commonly used in heavy-duty equipment for their design flexibility and superior power density. Compared to a conventional wind turbine transmission, a hydrostatic transmission (HST) is a lighter, more reliable, cheaper, continuously variable alternative for a wind turbine. In this paper, for the first time, a validated dynamical model and controlled experiment have been used to analyze the performance of a hydrostatic transmission with a fixed-displacement pump and a variable-displacement motor for community wind turbines. From the dynamics of the HST, a pressure control strategy is designed to maximize the power capture. A hardware-in-the-loop simulation is developed to experimentally validate the performance and efficiency of the HST drive train control in a 60 kW virtual wind turbine environment. The HST turbine is extensively evaluated under steady and time-varying wind on a state-of-the-art power regenerative hydrostatic dynamometer. The proposed controller tracks the optimal tip-speed ratio to maximize power capture

Dynamics and Control of an Energy-Efficient, Power-Regenerative, Hydrostatic Wind Turbine Dynamometer

Dynamometers are used to evaluate the real-world performances of drivetrains in various loading conditions. Due to its superior power density, high bandwidth, and design flexibility, a hydrostatic power-regenerative dynamometer is an ideal candidate for hydrostatic wind turbine transmission testing. A dynamometer can emulate the wind turbine rotor dynamics and allow the investigation of the performance of a unique hydrostatic drivetrain without actually building the physical system. The proposed dynamometer is an energy-efficient system with counter-intuitive control challenges. This paper presents the dynamics, control synthesis, and experimental validation of a power-regenerative hydrostatic dynamometer. A fourth-order non-linear model with three inputs was formulated for the dynamometer. The strength of input–output couplings was identified, and two different decoupling controllers were designed and implemented. During wind turbine testing, the synchronous generator turns at a constant speed and the system model is linear. A steady-state decoupling controller was developed for independent control of the drive and transmission. The implemented decoupling controller demonstrated a negligible change in rotor speed for a 40 bar step increase in pressure, but a 20 bar pressure spike for a 4 rpm step change in rotor speed. However, during starting and stopping, the synchronous generator speed is not constant, and the system model is nonlinear. Therefore, a steady-state decoupling controller will not work. Thus, a decentralized controller with feed-forward control and gain scheduling was designed and implemented. A reference command was designed to avoid cavitation, pressure spikes, and power flow reversal during start-up. The experimental results show precise tracking in steady-state and transient operations. The decentralized controller demonstrated a negligible change in rotor speed for a 40 bar step increase in pressure but a 100 bar pressure spike for a 4 rpm step increase in rotor speed. The pressure spike was reduced by 80 bar with the implementation of feed-forward gain. The proposed electro-hydro-mechanical system requires less power and has the potential to reduce energy expenditure by 50%