인체혈장 중 에탐부톨의 HPLC 분석법의 검증 및 단일용량 투여에 의한 약물동태 연구

곽혜선,박경호,최준식,송진아,성민경,장정옥,이화정 한국약제학회 2005 Journal of Pharmaceutical Investigation Vol.35 No.2

An HPLC method was employed for the determination of ethambutol in human plasma. After addition of internal standard (IS, octylamine, 2 μg/mL) and alkalinization of the plasma with 5 M sodium hydroxide, the drug and IS were extracted into the mixture of chloroform and diethyl ether (40:60, v/v). Following a 15-min vortex-mixing and a 10-min centrifugation, the organic phase was spiked with 100 pL of phenylethylisocyanate (2000 μg/mL) for chemical derivatization, mixed for 5 min and evaporated to dryness under a stream of nitrogen. The residue was reconstituted with 100 μL of mobile phase and 20 pL was injected into Cl8 column with a mobile phase consisting of methanol:water (70:30, v/v). The samples were detected utilizing an ultraviolet detector at 200 nm. The method was specific and validated with a limit of 0.15 μg/mL. Infra- and inter-day precision and accuracy were acceptable for all quality control samples including the lower limit of quantification. The applicability of this method was demonstrated by analysis of human plasma after oral administration of a single 1200-mg dose to 20 healthy subjects. From the plasma ethambutol concentration vs. time curves, the mean AUC was 9.61 ± 1.64 μg hr/mL. and Cmax of 2.68 μg/mL reached 2.73 hr after administration. The mean biological half-life of ethambutol was 3.46 ± 1.21 hr. Based on the results, this simple and validated assay could readily be used in any pharmacokinetic studies using humans.

수종 용제 중 퀘르세틴의 용해성 및 안정성

곽혜선,김혜원,전인구 한국약제학회 2004 Journal of Pharmaceutical Investigation Vol.34 No.1

The solubility and stability of quercetin in various vehicles were determined. The soubility of quercetin at 28℃ increased in the rank order of isopropyl myristate < oleyl alcohol < propylene glycol monocaprylate (PGMC) < polyethylene glycol-8 glyceryl linoleate < caprylocaproyl macrogol-6 glycerides < dietylene glycon mono ethy1 ether(DGME). The addition of DGME to non-aqueous vehicles such as PGL and PGMC markedly increased the solubility of quercetin. From the stability studies, it was found that quercetin was unstable due to rapid oxidation by dissoved oxygen. The addition of a combination of ascorbic acid and edetic acid (EDTA) at 0.1% markedly decreased the degrandation rates of quercetin in 40% polyethylene glycon 400 in saline. Quercetin was relatively unstable in non-aqueous vehicles such as PGL and PGMC alone, and PGL-PGMC co-solvent. The degradation of quercetin in such non-aqueous vehicles was fast, depending on temperature. The addition of butylated hydroxytoluene, butylated hydroxyanisole, citric acid and/or EDTA at 0.1% was effective in retarding the degradation of quercetin.

멜라토닌 플라스터의 제제설계 및 평가

곽혜선,김승웅,전인구 한국약제학회 2002 Journal of Pharmaceutical Investigation Vol.32 No.2

To investigate the feasibility of developing a novel melatonin plaster, the effects of vehicles and drug loading dose on the in vitro permeation of melatonin across dorsal hairless mouse skin from pressure-sensitive adhesive (PSA) matrices were examined. Vehicles employed were propylene glycol laurate (PGL), propylene glycol monocaprylate (PGMC) and diethylene glycol monoethyl ether (DGME). Among PSAs used, only Duro-Tak^?? 87-2196 showed a good peeling property. The release from Duro-Take^?? 87-2196 was proportional to the square root of time, and dose-dependent. The fluxes increased as the loading dose increased over the doses under solubility. The relatively high permeation flux (3.03±1.37 ㎍/㎠/hr) was obtained when using PGMC at the melatonin loading dose of 45 mg/140㎠. Lag time was not affected by the vehicles used but by the thickness spread. The melatonin plasters prepared using PGMC showed a good adhesive property onto skin, and showed no crystal formation.

용제 중 염산온단세트론의 용해성 및 안정성

곽혜선,오익상,전인구 한국약제학회 2003 Journal of Pharmaceutical Investigation Vol.33 No.1

The solubility and stability of ondansetron hydrochloride (OS) in various vehicles were determined. The effect of cyclodextrins (CD) on the solubility of OS in water was determined by equilibrium solubility method. The solubility of OS at 32℃ increase in the rank order of isopropyl myristate (IPM)<propylene glycol laurate (PGL)《 propylene glycol monolaurate<propylene glycol monocaprylate (PGMC)<poly(ethylene glycol) 400<diethylene glycol mono ethyl ether (DGME)<ethanol<poly(ethylene glycol) 300<water(36.1㎎/ml)《 propylene glycol (PG) (283㎎/ml). The addition of PG or DGME to non-aqueous vehicles such as IPM, PGL and PGMC markedly increased the solubility of OS. The addition of CDs in water increased the solubility. Apparent stability constant for the CD complexation with OS was calculated to be 25.5M^-1 for 2-hydroxypropyl-β-CD(2HPβCD0. Twenty mM β-CD, 69.4mM sulfobutyl ether β-CD and 115.4mM 2HPβCD increased the aqueous solubility of OS 1.27, 2.18 and 1.85 times, respectively. OS was stable in buffered aqueous solution (pH 5.0). However, OS was relatively unstable in non-aqueous vehicles in the order of PG<DGME<PGMC-DGME(60:40) co-solvent<PGMC. The degradation of OS in these vehicles was accelerated, depending on temperature.

오플록사신 및 리도카인 함유 수분 감응성 구강점막 패취제의 제조 및 방출 특성

곽혜선,송연화,전인구 韓國藥劑學會 2005 Journal of Pharmaceutical Investigation Vol.35 No.6

Effect of Vehicles and Enhancers on the In Vitro Permeation of Melatonin through Hairless Mouse Skin

곽혜선,김승웅,전인구 대한약학회 2002 Archives of Pharmacal Research Vol.25 No.3

테놀민 정(아테놀올 50㎎)에 대한 신일아테놀올 정의 생물학적 동등성

곽혜선,강성하,전인구 한국약제학회 2003 Journal of Pharmaceutical Investigation Vol.33 No.1

This study was conducted to compare the bioavailability of a generic product of Sinil Atenolol Tablets (Sinil Pharmaceutical Co., Ltd., Korea) with the innovator product, Tenormin^?? Tablets in 20 healthy Korean volunteers. The volunteers received a single 50㎎ dose of each atenolol formulation according to a randomized, two-way crossover design. Plasma samples were obtained over a 24-hour interval, and atenolol concentrations were determined by HPLC with a fluorescence detector. From the plasma atenolol concentration vs time curves, the following parameters were compared: area under the plasma concentration-time curve (AUC), peak plasma concentration (C_max), time to reach peak plasma concentration (T_max), and terminal first order elimination half-life (t_1/2). No statistically significant difference was obtained between the T_max values, and the logarithmic transformed AUC and C_max values of the two products. The 90% confidence for the ratio of the logarithmically transformed AUC and C_max values of Sinil Atenolol Tablets over those of Tenormin^?? Tablets were calculated to be between 0.99 and 1.07, and 1.04 and 1.16, respectively; both were within the bioequivalence limit of 0.80-1.25. The mean of T_max in Tenormin^?? Tablet group was 3.68 hour, and that in Sinil Atenolol Tablet group was 3.65 hour. The values of t_1/2 between the two products were found comparable, and the mean t_1/2 values of Tenormin^?? Tablets and Sinil Atenolol Tablets were 5.9 and 6.0 hour, respectively. Based on these results, it was concluded that Sinil Atenolol Tablets were comparable to Tenormin^?? Tablets in both the rate and extent of absorption, indicating that Sinil Atenolon Tablets were bioequivalent to the reference product, Tenormin^?? Tablets.

테놀민 정(아테놀올 50 mg)에 대한 신일아테놀올 정의 생물학적 동등성

곽혜선,강성하,전인구,Gwak, Hye-Sun,Kang, Sung-Ha,Chun, In-Koo 한국약제학회 2003 Journal of Pharmaceutical Investigation Vol.33 No.1

This study was conducted to compare the bioavailability of a generic product of Sinil Atenolol Tablets (Sinil Pharmaceutical Co., Ltd., Korea) with the innovator product, $Tenormin^{\circledR}$ Tablets in 20 healthy Korean volunteers. The volunteers received a single 50 mg dose of each atenolol formulation according to a randomized, two-way crossover design. Plasma samples were obtained over a 24-hour interval, and atenolol concentrations were determined by HPLC with a fluorescence detector. From the plasma atenolol concentration vs time curves, the following parameters were compared: area under the plasma concentration-time curve (AUC), peak plasma concentration $(C_{max})$, time to reach peak plasma concentration $(T_{max})$, and terminal first order elimination half-life $(t_{1/2})$. No statistically significant difference was obtained between the $T_{max}$ values, and the logarithmic transformed AUC and $C_{max}$ values of the two products. The 90% confidence for the ratio of the logarithmically transformed AUC and $C_{max}$ values of Sinil Atenolol Tablets over those of $Tenormin^{\circledR}$ Tablets were calculated to be between 0.99 and 1.07, and 1.04 and 1.16, respectively; both were within the bioequivalence limit of 0.80-1.25. The mean of $T_{max}$ in $Tenormin^{\circledR}$ Tablet group was 3.68 hour, and that in Sinil Atenolol Tablet group was 3.65 hour. The values of $t_{1/2}$ between the two products were found comparable, and the mean $t_{1/2}$ values of $Tenormin^{\circledR}$ Tablets and Sinil Atenolol Tablets were 5.9 and 6.0 hour, respectively. Based on these results, it was concluded that Sinil Atenolol Tablets were comparable to $Tenormin^{\circledR}$ Tablets in both the rate and extent of absorption, indicating that Sinil Atenolol Tablets were bioequivalent to the reference product, $Tenormin^{\circledR}$ Tablets

OECD-FAO 농업전망 2023-2032: 농식품 동향과 전망

곽혜선 한국농촌경제연구원 2024 세계농업 Vol.257 No.-

새로운 항혈전 약물인 아스팔라톤의 전처방화 연구

곽혜선(Hye Sun Gwak),전인구(In Koo Chun) 한국응용약물학회 2000 Biomolecules & Therapeutics(구 응용약물학회지) Vol.8 No.4

Physicochemical properties of aspalatone (acetylsalicylic acid maltol ester, AM), which has been recently found to have an antithrombotic effect, were studied in terms of solubility, dissolution, partition coefficient (Pc) and stability. The solubility of AM at 37℃ was about 1.2 mg/ml and the P_c value for n-octanol/ water and chloroform/water was 11.4 and 382.6, respectively. Dissolution rates of AM at pH 1.2 and 6.8 were more than 80% within 30 min. The degradation of AM followed apparent first-order kinetics, and was dependent on temperature, pH and ionic strength. From the pH-rate profile, the optimal pH was found to be at around 4.0. Half-lives at pH 1.2 and 6.8 were 33.5 and 44.4 hr, respectively. The degradation rate of AM at pH 1.2 was somewhat faster than that of aspirin, but at pH 7.0, the degradation rate of AM was slower than that of aspirin.