Development and in-vitro evaluation of an optimized carvedilol transdermal therapeutic system using experimental design approach

The effect of formulation variables on in-vitro release and permeation properties of carvedilol from transdermal patch was studied by varying one factor at a time as preliminary study.Based on these results,design of experiments technique was applied followed by regression analysis and response surface methodology to optimize formulation variables.Central Composite IV model design was used with four formulation variables:drug loading,matrix thickness,adhesive layer thickness,and propylene glycol concentration.Nineteen formulations were prepared according to the design;and the effect of formulation variables was studied on in-vitro release and permeation profiles of these formulations.In all cases,the permeation profiles paralleled in-vitro release profiles.The drug released at 7 h and 24 h was used as release response parameters while permeation flux obtained was employed as permeation response parameter.All four formulation variables were found to be significant for release properties and three of these exhibited significant effect on permeation profile of carvedilol across artificial membrane.Constrained optimization,using 47.9%of cumulative carvedilol released at 7 h and 99.8%at 24 h as well as 25.7 mg/cm2/h of permeation flux,was applied to obtain desired release and permeation profiles.Experimentally,carvedilol was observed to release from the optimized formulation with 51.4%drug release at 7 h and 98.5%at 24 h with an observed flux value of 27.4 mg/cm2/h across artificial membrane,which showed an excellent agreement with the predicted values.The results of this investigation show that the quadratic mathematical model developed could be used to further predict formulations with desirable release and permeation properties.

Search for electron-antineutrinos associated with gravitational-wave events GW150914,GW151012,GW151226,GW170104,GW170608,GW170814,and GW170817 at Daya Bay

The establishment of a possible connection between neutrino emission and gravitational-wave(GW)bursts is important to our understanding of the physical processes that occur when black holes or neutron stars merge.In the Daya Bay experiment,using the data collected from December 2011 to August 2017,a search was per-formed for electron-antineutrino signals that coincided with detected GW events,including GW150914,GW151012,GW151226,GW170104,GW170608,GW 170814,and GW 170817.We used three time windows of±10,±500,and±1000 s relative to the occurrence of the GW events and a neutrino energy range of 1.8 to 100 MeV to search for correlated neutrino candidates.The detected electron-antineutrino candidates were consistent with the expected background rates for all the three time windows.Assuming monochromatic spectra,we found upper limits(90%confidence level)of the electron-antineutrino fluence of(1.13-2.44)×10^(11)cm^(-2)at 5 MeV to 8.0×10^(7)cm^(-2)at 100 MeV for the three time w indows.Under the assumption of a Fermi-Dirac spectrum,the upper limits were found to be(5.4-7.0)×10^(9)cm^(2)for the three time windows.

Antineutrino energy spectrum unfolding based on the Daya Bay measurement and its applications

The prediction of reactor antineutrino spectra will play a crucial role as reactor experiments enter the precision era.The positron energy spectrum of 3.5 million antineutrino inverse beta decay reactions observed by the Daya Bay experiment,in combination with the fission rates of fissile isotopes in the reactor,is used to extract the positron energy spectra resulting from the fission of specific isotopes.This information can be used to produce a precise,data-based prediction of the antineutrino energy spectrum in other reactor antineutrino experiments with different fission fractions than Daya Bay.The positron energy spectra are unfolded to obtain the antineutrino energy spectra by removing the contribution from detector response with the Wiener-SVD unfolding method.Consistent results are obtained with other unfolding methods.A technique to construct a data-based prediction of the reactor antineutrino energy spectrum is proposed and investigated.Given the reactor fission fractions,the technique can predict the energy spectrum to a 2%precision.In addition,we illustrate how to perform a rigorous comparison between the unfolded antineutrino spectrum and a theoretical model prediction that avoids the input model bias of the unfolding method.