• Journal of Pharmaceutical Investigation
• /
• v.35 no.3
• /
• pp.179-185
• /
• 2005

Acebrophylline is a compound produced by salifying ambroxol with theophylline-7 -acetic acid. After acebrophylline administration, the salt splits into these two components which feature a peculiar pharmacokinetic behavior, an adequate ambroxol and a low theophylline-7-acetic acid serum levels. The purpose of the present study was to evaluate the bioequivalence of two acebrophylline capsules, Surfolase (Hyundai Pharm. lnd. Co., Ltd.) and Burophil (Kuhnil Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of ambroxol from the two acebrophylline formulations in vitro was tested using KP VIII Apparatus II method with various dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty eight healthy male subjects, $23.25{\pm}1.43$ years in age and $64.82{\pm}6.77$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After two capsules containing 100 mg as acebrophylline were orally administered, blood was taken at predetermined time intervals and the concentrations of ambroxol in serum were determined using HPLC with electrochemical detector (ECD). The dissolution profiles of two formulations were similar at all dissolution media. In addition, the pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug Surfolase, were -1.64, -3.33 and -0.92% for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 $(e.g., \;log\;0.93{\sim}log\;1.05\;and\;log\;0.88{\sim}log\;1.05$ for $AUC_t$, and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Burophil capsule was bioequivalent to Surfolase capsule.

• Proceedings of the Materials Research Society of Korea Conference
• /
• 2011.05a
• /
• pp.5-5
• /
• 2011

The research and development of hybrid electric vehicle (HEV), plug-in hybrid electric vehicle (PHEV) and electric vehicle (EV) are intensified due to the energy crisis and environmental concerns. In order to meet the challenging requirements of powering HEV, PHEV and EV, the current lithium battery technology needs to be significantly improved in terms of the cost, safety, power and energy density, as well as the calendar and cycle life. One new technology being developed is the utilization of composite cathode by mixing two different types of insertion compounds [e.g., spinel $LiMn_2O_4$ and layered $LiMO_2$ (M=Ni, Co, and Mn)]. Recently, some studies on mixing two different types of cathode materials to make a composite cathode have been reported, which were aimed at reducing cost and improving self-discharge. Numata et al. reported that when stored in a sealed can together with electrolyte at $80^{\circ}C$ for 10 days, the concentrations of both HF and $Mn^{2+}$ were lower in the can containing $LiMn_2O_4$ blended with $LiNi_{0.8}Co_{0.2}O_2$ than that containing $LiMn_2O_4$ only. That reports clearly showed that this blending technique can prevent the decline in capacity caused by cycling or storage at elevated temperatures. However, not much work has been reported on the charge-discharge characteristics and related structural phase transitions for these composite cathodes. In this presentation, we will report our in situ x-ray diffraction studies on this mixed composite cathode material during charge-discharge cycling. The mixed cathodes were incorporated into in situ XRD cells with a Li foil anode, a Celgard separator, and a 1M $LiPF_6$ electrolyte in a 1 : 1 EC : DMC solvent (LP 30 from EM Industries, Inc.). For in situ XRD cell, Mylar windows were used as has been described in detail elsewhere. All of these in situ XRD spectra were collected on beam line X18A at National Synchrotron Light Source (NSLS) at Brookhaven National Laboratory using two different detectors. One is a conventional scintillation detector with data collection at 0.02 degree in two theta angle for each step. The other is a wide angle position sensitive detector (PSD). The wavelengths used were 1.1950 ${\AA}$ for the scintillation detector and 0.9999 A for the PSD. The newly installed PSD at beam line X18A of NSLS can collect XRD patterns as short as a few minutes covering $90^{\circ}$ of two theta angles simultaneously with good signal to noise ratio. It significantly reduced the data collection time for each scan, giving us a great advantage in studying the phase transition in real time. The two theta angles of all the XRD spectra presented in this paper have been recalculated and converted to corresponding angles for ${\lambda}=1.54\;{\AA}$, which is the wavelength of conventional x-ray tube source with Cu-$k{\alpha}$ radiation, for easy comparison with data in other literatures. The structural changes of the composite cathode made by mixing spinel $LiMn_2O_4$ and layered $Li-Ni_{1/3}Co_{1/3}Mn_{1/3}O_2$ in 1 : 1 wt% in both Li-half and Li-ion cells during charge/discharge are studied by in situ XRD. During the first charge up to ~5.2 V vs. $Li/Li^+$, the in situ XRD spectra for the composite cathode in the Li-half cell track the structural changes of each component. At the early stage of charge, the lithium extraction takes place in the $LiNi_{1/3}Co_{1/3}Mn_{1/3}O_2$ component only. When the cell voltage reaches at ~4.0 V vs. $Li/Li^+$, lithium extraction from the spinel $LiMn_2O_4$ component starts and becomes the major contributor for the cell capacity due to the higher rate capability of $LiMn_2O_4$. When the voltage passed 4.3 V, the major structural changes are from the $LiNi_{1/3}Co_{1/3}Mn_{1/3}O_2$ component, while the $LiMn_2O_4$ component is almost unchanged. In the Li-ion cell using a MCMB anode and a composite cathode cycled between 2.5 V and 4.2 V, the structural changes are dominated by the spinel $LiMn_2O_4$ component, with much less changes in the layered $LiNi_{1/3}Co_{1/3}Mn_{1/3}O_2$ component, comparing with the Li-half cell results. These results give us valuable information about the structural changes relating to the contributions of each individual component to the cell capacity at certain charge/discharge state, which are helpful in designing and optimizing the composite cathode using spinel- and layered-type materials for Li-ion battery research. More detailed discussion will be presented at the meeting.

• Analytical Science and Technology
• /
• v.5 no.1
• /
• pp.41-49
• /
• 1992

An attempt was made to prepare two series of tetrakis eight-coordinate tungsten(IV) and cerium(IV) complexes containing the 5,7-dichloro-8-quinolinol(N:${\pi}$-acceptor atom, O:${\pi}$-donor atom) ligand. Tetrakis eight-coordinate tungsten(IV) complex of 2-mercaptopyrimidine(N:${\pi}$-acceptor atom, S:${\pi}$-donor atom) ligand have also been prepared. And the new series of mixed-ligand eight-coordinate tungsten(IV) complexes containing bidentate ligands 5,7-dichloro-8-quinolinol and 2-mercaptopyrimidine have been prepared, isolated by TLC and characterized. $W(dcq)_4$, $W(dcq)_3(mpd)_1$, $W(dcq)_2(mpd)_2$, $W(dcq)_1W(dcq)_3$ and $W(mpd)_4$ complexes of MLCT absorption band appeared to 710nm, 680nm, 625nm, 581nm, and 571nm(${\varepsilon}\;max={\sim}>{\times}10^4$) on low-energy respectively. The specific absorption wave length of $Ce(dcq)_4$ is appeared 520nm(${\varepsilon}\;max={\sim}>{\times}10^4$). The Chemical shift values by proton of coordinated position appeared to $W(dcq)_4$ [$H_2:8.9ppm$]; $W(dcq)_3(mpd)_1$ [$H_2:9.3$,$H_6:9.2ppm$]; $W(dcq)_2(mpd)_2$ [$H_2:9.7$,$H_6:8.95ppm$]; $W(dcq)_1(mpd)_3$ [$H_2:9.8$,$H_6:9.4ppm$]; $W(mpd)_4$ [$H_6:8.8ppm$]; $Ce(dcq)_4$ [$H_2:9.3ppm$] with $^1H$-NMR. The inertness of mixed-ligand eight coordinate tungsten(IV) complexes have been investigated by UV-Vis. spectroscopic method in dimethylsulfoxide at $90^{\circ}C$. The inertness of $W(dcq)_n(mpd)_{4-n}$ complexes showed the following order, $W(dcq)_3(mpd)_1;k_{obs.}=3.8{\times}10^{-6}$ > $W(mpd)_4;k_{obs.}=6.0{\times}10^{-6}$ > $W(dcq)_4;k_{obs.}=6.4{\times}10^{-6}$ > $W(dcq)_2(mpd)_2;k_{obs.}=7.0{\times}10^{-6}$ > $W(dcq)_1(mpd)_3;k_{obs.}=1.7{\times}10^{-5}$, which showed the inertness until 16days, 10days, 9days, 8days, and 4days. The $W(mpd)_4$ is very inert as $k_{obs.}=3.6{\times}10^{-6}$(16days) in xylene at $90^{\circ}C$ and $k_{obs.}=6.0{\times}10^{-6}$(10days) in DMSO at $90^{\circ}C$.