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Development of Nifedipine-loaded Coated Gelatin Microcapsule as a Long Acting Oral Delivery
Dong Xun Li,오동훈,강진양,최종서,우종수,용철순,최한곤,김종오,이원석,홍명자 대한약학회 2009 Archives of Pharmacal Research Vol.32 No.1
To develop the long acting nifedipine oral delivery with enhanced bioavailability, nifedipine-loaded gelatin microcapsule containing nifedipine and ethanol in gelatin shell was prepared using a spray-dryer, and then coated microcapsule was prepared by coating the gelatin microcapsule with Eudragit acrylic resin. The dissolution test and the bioavailability of the coated microcapsule in rats were evaluated compared to nifedipine powder. The amount of nifedipine dissolved from gelatin microcapsule for 30 min increased about 5-fold compared to nifedipine powder in pH 1.2 simulated gastric fluid. Nifedipine released from the coated microcapsule was retarded in pH 1.2 simulated gastric fluid compared with that from gelatin microcapsule. Furthermore, the coated gelatin microcapsule maintained the plasma level of nifedipine over 4 h and gave significantly higher AUC of nifedipine than nifedipine powder. Thus, the Eudragit-coated gelatin microcapsule, which could maintain the plasma level of nifedipine over a longer period without the initial burst-out plasma concentration, is a preferable delivery system for poorly water-soluble nifedipine.
Dong Xun Li,Myo Jeong Han,Prabagar Balakrishnan,Yi Dong Yan,Dong Hoon Oh,Jung Hyun Joe,Youngee Seo,김종오,Sang Man Park,Chul Soon Yong,최한곤 대한약학회 2010 Archives of Pharmacal Research Vol.33 No.1
The main purpose of this study was to evaluate the effect of a mixed drug solution containing a surfactant and β-cyclodextrin (β-CD) on the solubility and bioavailability of a poorly watersoluble drug, flurbiprofen. Solubility, dissolution and in vivo pharmacokinetics of flurbiprofen in the presence of surfactant, β-CD or mixture of surfactant and β-CD were investigated. Among the surfactants tested, Tween 80 produced the highest improvement in the aqueous solubility of flurbiprofen. The solubility of flurbiprofen increased linearly as a function of β-CD, resulting in B8 type that suggested a formation of inclusion complex in a molar ratio of 1:1. The solubility of flurbiprofen increased further when Tween 80 was included in addition to β-CD, suggesting that a micelle formation in the presence of Tween 80 was the likely reason for additional increase. Furthermore, the data suggested that Tween 80 did not interfere with the inclusion interaction between flurbiprofen and β-CD. The solubility of flurbiprofen was the highest in the mixed system containing 1.3 mM β-CD and 0.3% w/v Tween 80, and the maximum solubility of 160 μg/mL was achieved. Consistent with the enhanced solubility, the plasma exposure (both AUC and Cmax) of flurbiprofen when dosed as the mixed system was significantly higher (as much as 2 to 3-fold) than that without surfactant or β-CD, with surfactant alone, or with β-CD alone. Therefore, the mixed system consists of surfactant and β-CD could be used as an effective oral dosage form to improve bioavailability of poorly water soluble drugs such as flurbiprofen.
Li, Dong Xun,Jang, Ki-Young,Kang, Wonku,Bae, Kyoungjin,Lee, Mann Hyung,Oh, Yu-Kyoung,Jee, Jun-Pil,Park, Young-Joon,Oh, Dong Hoon,Seo, Youn Gee,Kim, Young Ran,Kim, Jong Oh,Woo, Jong Soo,Yong, Chul Soon Pharmaceutical Society of Japan 2010 Biological & pharmaceutical bulletin Vol.33 No.2
<P>To develop a novel sibutramine base-loaded solid dispersion with improved solubility bioavailability, various solid dispersions were prepared with water, hydroxypropylmethyl cellulose (HPMC), poloxamer and citric acid using spray-drying technique. The effect of HPMC, poloxamer and citric acid on the aqueous solubility of sibutramine was investigated. The physicochemical properties of solid dispersion were investigated using scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray powder diffraction. The dissolution and pharmacokinetics in rats of solid dispersion were evaluated compared to the sibutramine hydrochloride monohydrate-loaded commercial product (Reductil<SUP>®</SUP>). The sibutramine base-loaded solid dispersion gave two type forms. Like conventional solid dispersion system, one type appeared as a spherical shape with smooth surface, as the carriers and drug with relatively low melting point were soluble in water and formed it. The other appeared as an irregular form with relatively rough surface. Unlike conventional solid dispersion system, this type changed no crystalline form of drug. Our results suggested that this type was formed by attaching hydrophilic carriers to the surface of drug without crystal change, resulting from changing the hydrophobic drug to hydrophilic form. The sibutramine-loaded solid dispersion at the weight ratio of sibutramine base/HPMC/poloxamer/citric acid of 5/3/3/0.2 gave the maximum drug solubility of about 3 mg/ml. Furthermore, it showed the similar plasma concentration, area under the curve (<I>AUC</I>) and <I>C</I><SUB>max</SUB> of parent drug, metabolite I and II to the commercial product, indicating that it might give the similar drug efficacy compared to the sibutramine hydrochloride monohydrate-loaded commercial product in rats. Thus, this solid dispersion system would be useful to deliver poorly water-soluble sibutramine base with enhanced bioavailability.</P>
특집 : 동북3성과 한반도 경협의 비전과 과제: 한중 전략적 협력관계 내실화의 관점에서
박동훈 ( Dong Xun Piao ) 서울대학교 통일평화연구원 2013 통일과 평화 Vol.5 No.2
2009년 원자바오 총리 방북을 계기로 중국 동북3성과 북한간의 국경경제협력이 한층 더 심화 발전되고 있다. 그러나 현 시점에서 볼 때, 북핵문제는 갈수록 중국의 전략적 공간을 축소시키고 있으며 이는 궁극적으로 북·중 경협에도 영향을 미치고 있다. ‘정부 인도, 기업위주’의 경협방식도 기업의 수익성이 강조되면서 무역, 투자가 과도하게 지하 자원에 집중되는 현상을 보이고 있다. 특히 북한 사회의 시장인식 부족으로 중국 기업들의 대북투자 원동력이 높지 못하다. 전략적 협력동반자 관계 내실화의 시각에서 볼 때, 한·중 양국은 각자 이익에 기반을 둔 선순환적 공조관계를 수립하는 것이 필요하다. After the visit of Prime Minister Wen Jiabao in North Korea in 2009, cross-border economic cooperation between North Korea and three Northeastern provinces of China has been developing. However, at present the North Korean nuclear issue is likely to reduce the strategic space of China and consequently this has an effect on North Korean-Chinese economic cooperation. Since the economic cooperation system of “government-lead” and “enterprise-oriented” puts emphasis on profitability of the company, trade and investment excessively rely on natural resources. In particular, with the lack of awareness of North Korea`s market, it impedes a driving force of Chinese investment in North Korea. In terms of enhancement of the strategic cooperative partnership, Korea and China are necessary to forge a cyclical cooperative relationship based on the interests of their own.
( Yi Dong Yan ),( Jun Ho Sung ),( Dong Won Lee ),( Jung Su Kim ),( Eun Mi Jeon ),( Dae Duk Kim ),( Dong Wuk Kim ),( Jong Oh Kim ),( Ming Guan Piao ),( Dong Xun Li ),( Chul Soon Yong ),( Han Gon Choi ) 영남대학교 약품개발연구소 2012 영남대학교 약품개발연구소 연구업적집 Vol.22 No.0
Various amide prodrugs of salicylic acid were synthesised, and their physicochemical propertiesincluding lipophilicity, chemical stability and enzymatic hydrolysis were investigated. In vivo skinpermeation and accumulation profiles were also evaluated using a combination of common permeationenhancing techniques such as the use of a supersaturated solution of permeants in an enhancer vehicle, a lipophilic receptor solution, removal of the stratum corneum and delipidisation of skin. Their capacity factor values were proportional to the degree of carbon-carbon saturation in the side chain. All these amides were highly stable in acetonitrile and glycerine. Amide prodrugs were converted tosalicylic acid both in hairless mouse liver and skin homogenates. N-dodecyl salicylamide (C12SM) showed the lowest permeation of salicylic acid in skin compared to the other prodrugs, probably due to its low aqueous solubility. It had a high affinity for the stratum corneum and its accumulation was restricted to only the uppermost layer of skin. Thus, this amide prodrug could be a safer topicalsunscreen agent with minimum potential for systemic absorption.ⓒ2011 Elsevier B.V.All rights reserved.
Li, Dong Xun,Park, Jung-Gil,Han, Hong-Hee,Yang, Chan-Woo,Choi, Jun-Young,Oh, Dong-Hoon,Yong, Chul-Soon,Choi, Han-Gon The Korean Society of Pharmaceutical Sciences and 2007 Journal of Pharmaceutical Investigation Vol.37 No.5
Poorly water-soluble ibuprofen and ethanol can be encapsulated in gelatin microcapsule by spray drying technique. To select an optimal formula of ibuprofen-loaded gelatin microcapsule which increased the ethanol content and ibuprofen solubility with the decreased amount of gelatin in the microcapsules, in this study, the effect of gelatin, ibuprofen and sodium lauryl sulfate on the ibuprofen solubility and the amount of ethanol and ibuprofen encapsulated in the gelatin microcapsule were investigated. Ibuprofen solubility and the amount of ethanol encapsulated increased as gelatin and sodium lauryl sulfate increased, reached maximum at 4% and 0.6%, respectively and then followed a rapid decrease. Furthermore, the ibuprofen solubility and the encapsulated ibuprofen content increased as the amount of ibuprofen increased, reaching maximum at 0.5% and beyond that, there was no change in the solubility and ibuprofen content. However, the encapsulated ethanol content remained same irrespective of the amount of ibuprofen. On the basis of increased ibuprofen solubility, our results showed that the formula of ibuprofen-loaded gelatin microcapsule at the ratio of gelatin/ibuprofen/sodium lauryl sulfate/water/ethanol of 4/0.5/0.6/30/70 with ibuprofen solubility of about $290\;{\mu}g/mL$ and ethanol content of about $160\;{\mu}g/mg$ could be a potential oral delivery system for poorly water-soluble ibuprofen.
Kim, Dong Wuk,Yousaf, Abid Mehmood,Li, Dong Xun,Kim, Jong Oh,Yong, Chul Soon,Cho, Kwan Hyung,Choi, Han-Gon Elsevier 2017 Asian journal of pharmaceutical sciences Vol.12 No.1
<P>The purpose of the present research was to develop a suitable, simple, precise, accurate, robust, and reproducible RP-HPLC method for a reliable simultaneous quantification of docetaxel (DTX) and curcumin (CCM) in rat plasma samples using paclitaxel (PTX) as an internal standard. The samples were assayed by the Agilent 1260 Infinity HPLC instrument using a Capcell Pak C-8 column (4.6mmx 150 mm, 5 mu m) under isocratic conditions. The mobile phase consisted of acetonitrile and triple distilled water (40/60, v/v) with a flow rate of 1.0 ml/min. The eluent was monitored at 230 nm for simultaneous measurement of curcumin and docetaxel. The method was validated by determining system suitability, selectivity, sensitivity, linearity, inter-day and intra-day precision, accuracy, robustness, and stability in accordance with the guidelines of the United States Food and Drug Administration (FDA). The developed chromatographic method proved to be simple, precise, accurate, robust and reproducible. Moreover, the samples showed stability at room temperature over a period of 48 h. Thus, this method would be employed for routine simultaneous quantification of docetaxel and curcumin in rat plasma samples. (C) 2017 Shenyang Pharmaceutical University. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).</P>