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Shanmugam, Srinivasan,Park, Jae-Hyun,Chi, Sang-Cheol,Yong, Chul Soon,Choi, Han-Gon,Woo, Jong Soo Informa Healthcare 2011 Drug development and industrial pharmacy Vol.37 No.6
<P><I>Aim:</I> To investigate the physicochemical stability, pharmacokinetics (PK), and biodistribution of paclitaxel (PTX) from paclitaxel solid dispersion (PSD) prepared by supercritical antisolvent (SAS) process.</P><P><I>Methods:</I> Physicochemical stability was performed in accelerated (40°째C 70 ??±짹 ??5% RH) and stress (60°째C) storage conditions for a period of 6 months and 4 weeks, respectively. PK and biodistribution studies were performed in rats following i.v. administration of PTX equivalent to 6 and 12 ??mg/kg formulations.</P><P><I>Results:</I> Physical stability of PSD showed excellent stability with no recrystallization of the amorphous form. Chemical stability of PSD in terms of % PTX remaining was 98.2 ??±짹 ??0.6% at 6 months and 97.9 ??±짹 ??0.3% at 4 weeks of accelerated and stress conditions, respectively. The PK study showed a nonlinear increase in AUC with increasing dose, that is, 100% increase in dose (from 6 to 12 ??mg/kg) resulted in 405.90% increase in AUC. Unlike PK study, the organ distribution study of PTX from PSD showed linear relationship with dose escalation. The order of organ distribution of PTX from highest to lowest for both PSD and Taxol<SUP>®짰</SUP> was liver>kidney>lung>brain.</P><P><I>Conclusions:</I> This study demonstrated excellent physicochemical stability with insight information on the PK and biodistribution of PTX from PSD prepared by SAS process.</P>
Original Article : Zanamivir Oral Delivery: Enhanced Plasma and Lung Bioavailability in Rats
( Srinivasan Shanmugam ),( Ho Taek Im ),( Young Taek Sohn ),( Kyung Soo Kim ),( Yong Ll Kim ),( Chul Soon Yong ),( Jong Oh Kim ),( Han Gon Choi ),( Jong Soo Woo ) 영남대학교 약품개발연구소 2014 영남대학교 약품개발연구소 연구업적집 Vol.24 No.0
The objective of this study was to enhance the oral bioavailability (BA) of zanamivir (ZMR) by increasing its intestinal permeability using permeation enhancers (PE). Four different classes of PEs (Labrasol(®), sodium cholate, sodium caprate, hydroxypropyl β-cyclodextrin) were investigated for their ability to enhance the permeation of ZMR across Caco-2 cell monolayers. The flux and Papp of ZMR in the presence of sodium caprate (SC) was significantly higher than other PEs in comparison to control, and was selected for further investigation. All concentrations of SC (10-200 mM) demonstrated enhanced flux of ZMR in comparison to control. The highest flux (13 folds higher than control) was achieved for the formulation with highest SC concentration (200 mM). The relative BA of ZMR formulation containing SC (PO-SC) in plasma at a dose of 10 mg/kg following oral administration in rats was 317.65% in comparison to control formulation (PO-C). Besides, the AUC0-24 h of ZMR in the lungs following oral administration of PO-SC was 125.22 ± 27.25 ng hr ml(-1) with a Cmax of 156.00 ± 24.00 ng/ml reached at 0.50±0.00 h. But, there was no ZMR detected in the lungs following administration of control formulation (PO-C). The findings of this study indicated that the oral formulation PO-SC containing ZMR and SC was able to enhance the BA of ZMR in plasma to an appropriate amount that would make ZMR available in lungs at a concentration higher (>10 ng/ml) than the IC50 concentration of influenza virus (0.64-7.9 ng/ml) to exert its therapeutic effect.
The Effect of 1-Furan-2-yl-3-pyridine-2-yl-propenone on Pharmacokinetic Parameters of Warfarin
Srinivasan Shanmugam,이응석,정태천,용철순,최한곤,우종수,유봉규 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.7
1-Furan-2-yl-3-pyridine-2-yl-propenone (FPP-3) is an investigatory drug which has a dual inhibitory action on cyclooxygenase (COX) and 5-lipoxygenase (5-LOX). We examined its effect on the pharmacokinetics of warfarin. Three consecutive days of pretreatment with 17 mg/kg of FPP-3 had no significant effect on the pharmacokinetic parameters of warfarin when orally administered to rats. A higher dosage of FPP-3 however, did cause significant changes in the pharmacokinetic parameters of wafarin. The cytochrome P450 activity test demonstrated that the metabolism of R-warfarin was significantly inhibited by FPP-3 while there was little or no inhibition of the metabolism of S-warfarin, which is mainly responsible for its anticoagulant effect. Therefore, it appears that the alteration in the pharmacokinetic parameters of warfarin was due to the inhibitory effect of FPP-3 on the metabolism of R-warfarin. Although there was a significant increase in the plasma concentration, the area under the curve, half life of warfarin, and prothrombin time were not significantly changed. Based on these findings, the pharmacokinetic drug interaction between FPP-3 and warfarin mainly involves R-warfarin and, therefore, this interaction may not be of clinical significance in terms of warfarin-related toxicity.
( Srinivasan Shanmugam ),( Young Hun Kim ),( Jeong Hee Park ),( Ho Taek Im ),( Young Taek Sohn ),( Kyeong Soo Kim ),( Yong Ll Kim ),( Chul Soon Yong ),( Jong Oh Kim ),( Han Gon Choi ),( Jong Soo Woo ) 영남대학교 약품개발연구소 2014 영남대학교 약품개발연구소 연구업적집 Vol.24 No.0
Aim: The main objective was to investigate the in vitro release profile/kinetics, and in vivo plasma pharmacokinetics (PK) and organ biodistribution (BD) of the prepared sildenafil vaginal suppositories (SVS). Methods: Suppositories containing 25mg of sildenafil were prepared by the cream melting technique using Witepsol H-15 as a suppository base. The suppositories were characterized for weight variation, content uniformity, hardness, disintegration time and crystallinity change. The in vitro dissolution in pH 4.5, and in vivo plasma PK and organ BD of sildenafil from SVS in female Sprague Dawley rats, were also investigated. Results: The mean weight variation, content uniformity, hardness and disintegration time of the prepared SVS were 1.127±0.020g, 98.25±2.50%, 2.5±0.08kg and 9±1.0min, respectively. The release of sildenafil from the SVS was more than 90% at 30min, with a release kinetic of Hixson--Crowell model and non-Fickian diffusion (n=0.464). The plasma PK study demonstrated a significantly lower Cmax (∼10 times) and AUC0-24h (∼13 times) of sildenafil in plasma following intravaginal (IVG) administration of suppositories compared to oral (PO) administration of sildenafil solution. Nevertheless, the organ BD study showed a phenomenally higher Cmax (∼40 times) and AUC0-24h (∼20 times) of sildenafil in uterus following IVG administration of suppositories than PO administration of sildenafil solution. Conclusion: This study demonstrated enhanced sildenafil exposure in the uterus following IVG administration of SVS, which could be used to target the uterus for therapeutic benefits.
( Srinivasan Shanmugam ),( Rengarajan Baskaran ),( Prabagar Balakrishnan ),( Pritam Thapa ),( Chul Soon Yong ),( Bong Kyu Yoo ) 영남대학교 약품개발연구소 2012 영남대학교 약품개발연구소 연구업적집 Vol.22 No.0
The objectives of this study was to prepare solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing phosphatidylcholine (PC), an endogenous phospholipid with excellent in vivo solubilization capacity, as oil phase for the delivery of bioactive carotenoid lutein, by spray drying the SNEDDS (liquid system) containing PC using colloidal silica (Aerosil® 200 VV Pharma) as the inertsolid carrier, and to evaluate the enhanced bioavailability (BA) of lutein from S-SNEDDS. The droplet size analyses revealed droplet size of less than 100 nm. The solid state characterization of S-SNEDDS by SEM, DSC, and XRPD revealed the absence of crystalline lutein in the S-SNEDDS. The bioavailability study performed in rabbits resulted in enhanced values of C(max) and AUC for S-SNEDDS. The enhancement of C(max) for S-SNEDDS was about 21-folds and 8-folds compared with lutein powder (LP) and commercial product (CP), respectively. The relative BA of S-SNEDDScompared with CP or LP was 2.74-folds or 11.79-folds, respectively. These results demonstrated excellent ability of S-SNEDDS containing PC as oil phase to enhance the BA of lutein in rabbits. Thus, S-SNEDDS containing PC as oil phase could be a useful lipid drug delivery system for enhancing the BA of lutein in vivo.
Zanamivir Oral Delivery: Enhanced Plasma and Leng Bioavailability in Rats
( Srinivasan Shanmugam ),( Ho Taek Im ),( Young Taek Sohn ),( Kyung Soo Kim ),( Yong Il Kim ),( Chul Soon Yong ),( Jong Oh Kim ),( Han Gon Choi ),( Jong Soo Woo ) 한국응용약물학회 2013 Biomolecules & Therapeutics(구 응용약물학회지) Vol.21 No.2
The objective of this study was to enhance the oral bioavailability (BA) of zanamivir (ZMR) by increasing its intestinal permeabil-ity using permration enhancers (PE). Four different classes of PEs (Ladrasol, sodium cholate, sodium caprate, hydroxypropyl β-cyclodextrin) were investigated for their ability to enhance the permeation of ZMR across Caco-2 cell monolayers. The flux and Papp-of ZMR in the presence of sodium caprate (SC) was signifecantly higher than other PEs in cimpartson to control, and was selected for further investigation. All concentrations of SC (10-200 mM) deminstrated enhanced flux of ZMR in comparison to cintrol. The highest flux (13 folds higher than control) was achieved for the formulation with highest SC concentration (200 mM). Thw relative BA of ZMR fomulation containing SC (PO-SC) in plasma at a dose of 10 mg/kg gollowing oral administration in rats was 317. 65% in comparison tocontrol formulation (PO-C). Besides, the AUC0-24 h of ZMR in the lungs following oral administra tion of PO-SC containing ZMR and SC was sdle to enhance the BA of ZMR in plasma to an approate amount that would make ZMR available in lungs at a concentration hegher (>10 ng/ml) than the LC50 concentration of ingluenza virus (0. 64-7. 9 ng/ml) to exert its therapeutic effect.