Formulation and Evaluation of Tramadol HCl Matrix Tablets Using Carbopol 974P and 934 as Rate-Controlling Agents

Purpose: To formulate and prepare controlled release (CR) matrix tablets of tramadol HCl using Carbopol 974P and 934 polymers as rate-controlling agents.Methods: The tablets were prepared by direct compression method using various drug to polymer (D:P) ratios. Co-excipients, including carboxymethylcellulose, starch and/or hydroxypropyl methylcellulosewere also used to modulate the formulations. Various physical tests and in vitro dissolution studies were carried out on the formulations. The dissolution data were subjected to various release modelsResults: As the concentration of the polymer (rate-controlling agent) increased, dissolution rate decreased, For the formulation containing Carbopol 974P at D:P ratio of 10:7, drug release decreased to 83 % compared with the release rate of 99 % for the formulation with D:P ratio of 10:3. Kinetic analysis indicates that drug release mechanism was anomalous non-Fickian diffusion.Conclusion: Both Carbopol 974P and 934 can be used as rate-controlling agents in the formulation of tramadol HCl CR tablets. Appropriate selection of drug/polymer ratio can be applied effectively to modulate the dissolution rate of the drug.Keywords: Tramadol, Carbopol, Carboxymethylcellulose (CMC), Hydroxypropyl methylcellulose, Controlled releas

Entropy generation in magnetohydrodynamic radiative non-Newtonian dissipative convection flow from an inclined plane : numerical study

A theoretical model is developed to study entropy generation in non-Newtonian magnetohydrodynamic thermal convection from an inclined plate as a simulation of electroconductive polymer materials processing of relevance to automotive coating applications. High temperature invokes radiative effects which are analysed with the Rosseland diffusion flux approximation. The Jeffery’s viscoelastic model is deployed to describe the non-Newtonian characteristics of the fluid and provides a good approximation for magnetic polymers, which constitutes a novelty of the present work. The normalized nonlinear boundary value problem is solved computationally with the Keller-Box implicit finite-difference technique. Extensive solutions for velocity, surface temperature, skin friction and heat transfer rate are visualized graphically for various thermophysical parameters. Validation is conducted with earlier published work for the case of a vertical plate in the absence of magnetic field, radiative flux and non-Newtonian effects. The dimensionless entropy generation is obtained via the reduced momentum and energy equations. Bejan number is generally decreased with greater values of Deborah number. Increasing magnetic field reduces entropy generation number whereas it enhances the Bejan number. Increasing Brinkman number (dissipation parameter) is found to enhance the entropy generation number whereas it suppresses the Bejan number

Tixagevimab–cilgavimab for treatment of patients hospitalised with COVID-19: a randomised, double-blind, phase 3 trial

Background: Tixagevimab–cilgavimab is a neutralising monoclonal antibody combination hypothesised to improve outcomes for patients hospitalised with COVID-19. We aimed to compare tixagevimab–cilgavimab versus placebo, in patients receiving remdesivir and other standard care. Methods: In a randomised, double-blind, phase 3, placebo-controlled trial, adults with symptoms for up to 12 days and hospitalised for COVID-19 at 81 sites in the USA, Europe, Uganda, and Singapore were randomly assigned in a 1:1 ratio to receive intravenous tixagevimab 300 mg–cilgavimab 300 mg or placebo, in addition to remdesivir and other standard care. Patients were excluded if they had acute organ failure including receipt of invasive mechanical ventilation, extracorporeal membrane oxygenation, vasopressor therapy, mechanical circulatory support, or new renal replacement therapy. The study drug was prepared by an unmasked pharmacist; study participants, site study staff, investigators, and clinical providers were masked to study assignment. The primary outcome was time to sustained recovery up to day 90, defined as 14 consecutive days at home after hospital discharge, with co-primary analyses for the full cohort and for participants who were neutralising antibody-negative at baseline. Efficacy and safety analyses were done in the modified intention-to-treat population, defined as participants who received a complete or partial infusion of tixagevimab–cilgavimab or placebo. This study is registered with ClinicalTrials.gov, NCT04501978 and the participant follow-up is ongoing. Findings: From Feb 10 to Sept 30, 2021, 1455 patients were randomly assigned and 1417 in the primary modified intention-to-treat population were infused with tixagevimab–cilgavimab (n=710) or placebo (n=707). The estimated cumulative incidence of sustained recovery was 89% for tixagevimab–cilgavimab and 86% for placebo group participants at day 90 in the full cohort (recovery rate ratio [RRR] 1·08 [95% CI 0·97–1·20]; p=0·21). Results were similar in the seronegative subgroup (RRR 1·14 [0·97–1·34]; p=0·13). Mortality was lower in the tixagevimab–cilgavimab group (61 [9%]) versus placebo group (86 [12%]; hazard ratio [HR] 0·70 [95% CI 0·50–0·97]; p=0·032). The composite safety outcome occurred in 178 (25%) tixagevimab–cilgavimab and 212 (30%) placebo group participants (HR 0·83 [0·68–1·01]; p=0·059). Serious adverse events occurred in 34 (5%) participants in the tixagevimab–cilgavimab group and 38 (5%) in the placebo group. Interpretation: Among patients hospitalised with COVID-19 receiving remdesivir and other standard care, tixagevimab–cilgavimab did not improve the primary outcome of time to sustained recovery but was safe and mortality was lower. Funding: US National Institutes of Health (NIH) and Operation Warp Speed

Do Islamic indices provide diversification to bitcoin? A time-varying copulas and value at risk application

This is an accepted manuscript of an article published by Elsevier in Pacific-Basin Finance Journal on 08/04/2020, available online: https://doi.org/10.1016/j.pacfin.2020.101326 The accepted version of the publication may differ from the final published version.© 2020 The emergence of new asset classes offers avenues to international investment community however understanding relationship between any two assets in a single portfolio is important. We investigate the risk dependence between daily Bitcoin and major Islamic equity markets spanning over from July 2010 to March 2018. We start by examining long memory properties of Bitcoin and sampled Islamic indices and report significant results. The residuals from fractionally integrated models are then used in bivariate time invariant and time varying copulas to investigate dependence structure. Among all Islamic indices, DJIUK, DJIJP and DJICA exhibit time varying dependence with Bitcoin. In addition, we apply VaR, CoVaR and ΔCoVaR as risk measure to examine spillover between Bitcoin and Islamic equity markets. VaR of Bitcoin exceeds from VaR of Islamic indices and CoVaR of both Islamic and Bitcoin exceeds their respective VaR, suggesting presence of risk spillover between each other. Our results also report asymmetry between downside and upside ΔCoVaR suggesting implications for investors with different risk preferences. Finally, the diversification benefits indicate that Islamic equity market serves as an effective hedge in a portfolio along with Bitcoin.Accepted versio

Inclusive and multiplicity dependent production of electrons from heavy-flavour hadron decays in pp and p-Pb collisions

Measurements of the production of electrons from heavy-flavour hadron decays in pp collisions at root s = 13 TeV at midrapidity with the ALICE detector are presented down to a transverse momentum (p(T)) of 0.2 GeV/c and up to p(T) = 35 GeV/c, which is the largest momentum range probed for inclusive electron measurements in ALICE. In p-Pb collisions, the production cross section and the nuclear modification factor of electrons from heavy-flavour hadron decays are measured in the p(T) range 0.5 < p(T) < 26 GeV/c at root s(NN) = 8.16 TeV. The nuclear modification factor is found to be consistent with unity within the statistical and systematic uncertainties. In both collision systems, first measurements of the yields of electrons from heavy-flavour hadron decays in different multiplicity intervals normalised to the multiplicity-integrated yield (self-normalised yield) at midrapidity are reported as a function of the self-normalised charged-particle multiplicity estimated at midrapidity. The self-normalised yields in pp and p-Pb collisions grow faster than linear with the self-normalised multiplicity. A strong p(T) dependence is observed in pp collisions, where the yield of high-p(T) electrons increases faster as a function of multiplicity than the one of low-p(T) electrons. The measurement in p-Pb collisions shows no p(T) dependence within uncertainties. The self-normalised yields in pp and p-Pb collisions are compared with measurements of other heavy-flavour, light-flavour, and strange particles, and with Monte Carlo simulations

K0SK0S and K0SK± femtoscopy in pp collisions at √s = 5.02 and 13 TeV

Femtoscopic correlations with the particle pair combinations (KSKS0)-K-0 and (KSK +/-)-K-0 are studied in pp collisions at root s= 5.02 and 13 TeV by the ALICE experiment. At both energies, boson source parameters are extracted for both pair combinations, by fitting models based on Gaussian size distributions of the sources, to the measured two-particle correlation functions. The interaction model used for the (KSKS0)-K-0 analysis includes quantum statistics and strong final-state interactions through the f(0) (980) and a(0) (980) resonances. The model used for the (KSK +/-)-K-0 analysis includes only the final-state interaction through the a(0) resonance. Source parameters extracted in the present work are compared with published values from pp collisions at root s = 7 TeV and the different pair combinations are found to be consistent. From the observation that the strength of the (KSKS0)-K-0 correlations is significantly greater than the strength of the (KSK +/-)-K-0 correlations, the new results are compatible with the a(0) resonance being a tetraquark state of the form (q(1), (q(2)) over bar, s, (s) over bar), where q(1) and q(2) are uor d quarks. (C) 2022 European Organization for Nuclear Research, ALICE. Published by Elsevier B.V

Hypertriton Production in p-Pb Collisions at √sNN = 5.02 TeV

The study of nuclei and antinuclei production has proven to be a powerful tool to investigate the formation mechanism of loosely bound states in high-energy hadronic collisions. The first measurement of the production of ${\rm ^{3}_{\Lambda}\rm H}$ in p-Pb collisions at $\sqrt{s_{\rm{NN}}}$ = 5.02 TeV is presented in this Letter. Its production yield measured in the rapidity interval -1 < y < 0 for the 40% highest multiplicity p-Pb collisions is ${\rm d} N /{\rm d} y =[\mathrm{6.3 \pm 1.8 (stat.) \pm 1.2 (syst.) ] \times 10^{-7}}$. The measurement is compared with the expectations of statistical hadronisation and coalescence models, which describe the nucleosynthesis in hadronic collisions. These two models predict very different yields of the hypertriton in small collision systems such as p-Pb and therefore the measurement of ${\rm d} N /{\rm d} y$ is crucial to distinguish between them. The precision of this measurement leads to the exclusion with a significance larger than 6$\sigma$ of some configurations of the statistical hadronisation, thus constraining the production mechanism of loosely bound states

Measurement of the non-prompt D-meson fraction as a function of multiplicity in proton-proton collisions at s \sqrt{s} = 13 TeV

The fractions of non-prompt (i.e. originating from beauty-hadron decays) D0 and D+ mesons with respect to the inclusive yield are measured as a function of the charged-particle multiplicity in proton-proton collisions at a centre-of-mass energy of √s = 13 TeV with the ALICE detector at the LHC. The results are reported in intervals of transverse momentum (pT) and integrated in the range 1 < pT < 24 GeV/c. The fraction of non-prompt D0 and D+ mesons is found to increase slightly as a function of pT in all the measured multiplicity intervals, while no significant dependence on the charged- particle multiplicity is observed. In order to investigate the production and hadronisation mechanisms of charm and beauty quarks, the results are compared to PYTHIA 8 as well as EPOS 3 and EPOS 4 Monte Carlo simulations, and to calculations based on the colour glass condensate including three-pomeron fusion

K∗(892)0 and φ(1020) production in p-Pb collisions at √s NN = 8.16 TeV

The production of K*(892)(0) and phi(1020) resonances has been measured in p-Pb collisions at root s(NN) = 8.16 TeV using the ALICE detector. Resonances are reconstructed via their hadronic decay channels in the rapidity interval -0.5 8 GeV/c), the R-pPb values of all hadrons are consistent with unity within uncertainties. The R-pPb of K*(892)(0) and phi(1020) at root s(NN) = 8.16 and 5.02 TeV show no significant energy dependence