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

수용액중 염산카로베린의 용해성 및 안정성

곽혜선(Hye Sun Gwak),이동수(Dong Soo Lee),전인구(In Koo Chun) 한국약제학회 1998 Journal of Pharmaceutical Investigation Vol.28 No.2

N/A The solubility and physicochemical stability of caroverine hydrochloride (CRV), an antispasmodic, in buffered aqueous solutions were studied using a reverse phase high performance liquid chromatography. The solubility of the drug at pH 2.76-5.40 was similar at the range 31.9-36.2 ㎎/㎖ (34℃), but, at the pH higher than 6.0, markedly decreased. The use of polyethylene glycol 400 as a cosolvent did not increase the solubility at any compositions examined. Moreover, increasing molar concentration of aqueous phosphate buffer from 0 to 0.5 M remarkably decreased the solubility. The degradation of CRV followed the apparent first-order kinetics. The degradation was accelerated with decreasing pH and increasing storage temperature. The half-lives for the degradation. of CRV (1.0 ㎎/㎖) at pH 1.28, 4.01. and 5.93 (45℃) were 2.8, 31.4 and 124 hr. respectively. The pHs of incubated solutions were to some extent lowered perhaps due to the formation of acidic degradation products. The addition of disodium edetate (0.01%) to the CRV solution (pH 4.95) retarded 2.5 times the degradation rate at 45℃, but the use of sodium bisulfite (0.1%) accelerated 2.9 times the rate. The activation energy for the CRV solution (20 ㎎/㎖, pH 5.4) containing 0.01% EDTA was calculated to be 5.98㎉/mole. When the solution was stored under nitrogen displacement in ampoule, there was no significant degradation even after 3 months at 40℃, indicating that protection from oxidation by air (oxygen) is essential for the complete stabilization of CRV solution.

수용액중 시클로덱스트린류가 아스팔라톤의 용해성과 안정성에 미치는 영향

곽혜선(Hye Sun Gwak),전인구(In Koo Chun) 한국약제학회 2000 Journal of Pharmaceutical Investigation Vol.30 No.4

The effect of cyelodextrins on the solubility and stability of aspalatone (acetylsalicylic acid maltol ester, AM, CAS 147249-33-0), which has been recently found to have an antithrombotic effect, was investigated. The addition of β-cylodextdn (β-CD), dimetltyl-β-cyclodextrin (DMCD) or 2-hydroxypropyl-β-cyclodextrin (HPCD) to the aqueous solution increased the solubility of AM concentration-dependently. From the phase solubility diagram, stability constants for AM-β-CD, -DMCD or -HPCD complexes were calculated to be 43.1, 78.3 and 53.0 M^(-1). The addition of β-CD, DMCD or HPCD to AM solution retarded the degradation rate of AM in the acidic region. However, β-CD and HPCD rather acted as an accelerator of degradation in the neutral and alkaline regions. DMCD had a stabilizing effect at all pHs studied.

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.

토끼의 비강 , 직장 및 질 점막을 통한 로이신엔케팔린과 〔 D-알라2 〕 - 로이신엔케팔린아미드의 투과 증진

곽혜선(Hye Sun Gwak),박인숙(In Sook Park),전인구(In Koo Chun) 한국응용약물학회 2002 Biomolecules & Therapeutics(구 응용약물학회지) Vol.10 No.2

N/A The effects of enzyme inhibitors and penetration enhancers on the permeation of leucine enkephalin (Leu-Enk) and its synthetic analog, [D-ala^2]-leucine enkephalinamide (YAGFL) across the nasal, rectal and vaginal mucosae were evaluated. Enzyme inhibitors and penetration enhancers employed for Leu-Enk permeation study were amastatin (AM), thimerosal (TM) and ethylenediaminetetraacetic acid disodium salt (EDTA), and sodium taurodihydrofusidate (STDHF). Those for YAGFL permeation study were TM, benzalkonium chloride (BC) and EDTA, and STDHF, sodium deoxycholate (SDC), sodium glycholate (SGC), glycyrrhizic acid ammonium salt (GAA), L-α-lysophosphatidylcholine (LPC) and mixed micelle (MM, STDHF : linoleic acid = 15 mM : 5 mM), The addition of TM alone on the donor and receptor solutions for Leu-Enk permeation study across all the three kinds of mucosae failed to inhibit the degradation; it completely degraded in 6 hrs, and no permeation occurred. However, with addition of three kinds of inhibitors together, the fluxes across nasal, rectal and vaginal mucosae were 20.7±2.5, 0.3±0.05 and 1.4±0.5 ㎍/㎠/hr, respectively. Moreover, the addition of STDHF in the presence of the above three inhibitors enhanced permeation across nasal, rectal and vaginal mucosae 1.3, 15 and 1.3 times, respectively. YAGFL also degraded in the donor and receptor solutions rapidly as time went. With mixed inhibitors of TM and EDTA, the percents of YAGFL remaining in the donor solutions facing nasal, rectal and vaginal mucosae were 69.7, 69.8 and 79.8%, respectively; the percent permeated increased to 10, 2.1 and 5.7%, respectively. The addition of STDHF in the presence of either BC/EDTA or TM/EDTA increased the permeation 2.2, 11.0 and 2.9 times, and 2.21, 14.0 and 2.7 times for nasal, rectal and vaginal mucosae, respectively. With SDC, SGC, GAA, LPC and MM in the presence of TM/EDTA increased permeation; especially, they increased permeation across vaginal mucosae effectively, and the enhancement factors were 12.5, 7.6, 8.7, 5.7 and 5.5, respectively. The degradation extent of YAGFL was correlated with protein concentrations in the epidermal and serosal extracts. The flux of YAGFL across nasal mucosa increased dose-dependently.

아세틸살리실산말톨 에스텔의 피부투과 촉진

전인구(In Koo Chun),곽혜선(Hye Sun Gwak) 한국응용약물학회 1996 학술대회 Vol.1996 No.1

N/A

원보 : Levodopa의 이온토포레시스 경피전달: 올레인산 마이크로에멀젼 및 에탄올의 투과증진

정신애 ( Shin Ae Jung ),곽혜선 ( Hye Sun Gwak ),전인구 ( In Koo Chun ),오승열 ( Seaung Youl Oh ) 한국약제학회 2008 Journal of Pharmaceutical Investigation Vol.38 No.6

비페닐디메칠디카르복실레이트 연질캅셀제의 설계 및 제제학적 평가

전인구(In Koo Chun),곽혜선(Hye Sun Gwak),문지현(Jee Hyun Moon) 한국응용약물학회 1996 Biomolecules & Therapeutics(구 응용약물학회지) Vol.4 No.4

To solubilize practically insoluble biphenyl dimethyl dicarboxylate (DDB), which has been used for the treatment of chronic hepatitis as tablets or hard capsules, the solubilities of DDB in various hydrophilic, oily and hydrocarbon vehicles, and aqueous surfactant solutions were measured by high performance liquid chromatography. It was found that, among the vehicles studied, polyethylene glycol (PEG) 300 revealed the best solvency, and the solubility reached 17.6 ㎎/ml at 37℃. The addition of glycyrrhizic acid ammonium salt (GAA) to DDB-PEG 300 solution (5-20 ㎎/g) inhibited the formation of precipitates, and at the concentration of 10 ㎎/g, any precipitation was not observed even after 2 years at 4℃. Furthermore, GAA markedly enhanced the permeation of DDB through the rabbit duodenal mucosa in a concentration dependent manner. The addition of copolyvidone (ca. 1.0%) to DDB-GAA-PEG 300 system (1: 0.5 : 97.5 w/w) was most effective in preventing the considerable precipitation of DDB-PEG 300 solution (7.5 mg/750㎎) when mixed with water of 300-900 ml at 37℃. GAA showed a synergistic effect in the prevention of precipitate formation. This finding suggests that this DDB formulation may form less precipitation when DDB soft capsules disintegrate and diffuse into the gastrointestinal fluid, resulting in improving the bioavailability. Dissolution rate of DDB (7.5 ㎎) from soft elastic capsules of DDB-GAA-PEG 300 system was rapid. The supersaturation state was maintained for 2 hr at the concentration of 7.35±3.3㎎ in 900 ml of water without precipitation. The total amount of DDB dissolved from this new formulation was 5.3 and 6.1 times higher, when compared to marketed DDB tablets (25 ㎎) and capsules (7.5 ㎎), respectively.

수분 감응성 아시클로버 패취제의 설계 및 평가

김아미 ( Ah Mee Kim ),곽혜선 ( Hye Sun Gwak ),전인구 ( In Koo Chun ) 한국약제학회 2006 Journal of Pharmaceutical Investigation Vol.36 No.6

아스팔라톤의 토끼 위장관 점막 투과 및 효소적 분해

전인구(In Koo Chun),곽혜선(Hye Sun Gwak) 한국약제학회 2001 Journal of Pharmaceutical Investigation Vol.31 No.1

N/A To evaluate the site-specific permeation of aspalatone (acetylsalicylic acid maltol ester, AM) through gastrointestinal tract, the enzymatic degradation and permeation studies were carried out using gastric, duodenal and jejunal mucosae of rabbits. It was found that 15.2±11.4%, 11.6±5.2 and 0.8±0.6% of the donor dose of AM, salicylmaltol (SM) and aspirin (ASA) permeated through the upper gastric mucosa after 8 hr of permeation, respectively. After 8 hr of AM permeation, SM and ASA were measured to be 15.0±1.7 and 2.6±0.8% of the dose in the donor solutions, respectively, and salicylic acid (SA) was not detected even after 6 hr, suggesting a very low gastric damage. For the gastric mucosa, the increase of donor dose from 100 to 1,000 ㎍/㎖ increased the permeation flux dose-dependently (r=0.9905). For the duodenal and jejunal mucosae, however, AM was fully degraded into SM and SA due to the esterase activities within 30 min. AM and ASA were not detected in the receptor solution. This result indicates that AM is not a prodrug of ASA. Addition of potassium fluoride (0.5%) into the donor solution delayed the degradation of AM, but did not allow the permeation through duodenal mucosa even by the inhibition of esterase activity. The addition of dimethyl-β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin (5%) into the donor solutions also did not show favorable effects on the permeation of AM through various mucosa. In comparison of permeation rates of AM and ASA through the upper gastric mucosa, the flux of ASA was 4.2 times faster than AM based on the molar concentration. ASA also was fully degraded in the donor solutions faced with duodenal and jejunal mucosa within 2 hr, and was not detected in the receptor solution, suggesting a slower metabolism compared with AM.