모티리움 엠정(말레인산돔페리돈 12.72 mg)에 대한 한미 돔페리돈정의 생물학적 동등성

곽손혁,우종수,황성주 충남대학교 약학대학 의약품개발연구소 2002 藥學論文集 Vol.17 No.-

Bioequivalence of two domperidone maleate tablets, test drug (Hanmi Domperidone^ⓡ tablet: Hanmi Pharmaceutical Co.) and reference drug (Motilium-M^ⓡ tablet: Jassen Korea Pharm. Co.), was evaluated according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty four healthy male volunteers were divided randomly into two groups and administered the drug orally at the dose of 20㎎ as domperidone in a 2×2 crossover study. There was a week washout period between administrations. Blood samples were taken at predetermined time intervals for 48hr and the plasma concentration of domperidone was determined by a HPLC method. AUC_0-48hr (area under the plasma concentration-time curve from time zero to 48hr), C_max (maximum plasma drug concentration) and T_max, (time to reach C_max) were estimated from the plasma drug concentration-time data. Analysis of variance (ANOVA) revealed no difference in AUC_0-48hr, C_max and T_max between two products. The apparent differences of these parameters between two products were less than 20% (i.e., 1.047, -0.416 and 9.347% for AUC_0-10hr, C_max and T_max, respectively). The powers (1-β) for AUC_0-48hr, C_max and T_max were over 0.99. Minimal detectable differences (Δ) at α=0.05, 1-β=0.8 were less than 20% (i.e. 11.15, 10.21 and 18.13% for AUC_0-10hr, C_max and T_max respectively). The 95% Confidence intervals (δ) for these parameters were also within ±20% (i.e. -5.49≤δ≤7.58, -6.39≤δ≤5.57 and -1.28≤δ≤19.95 for AUC_0-10hr, C_max and T_max, respectively). These results satisfied the criteria of KFDA guidelines for bioequivalence, indicating the two tablets of domperidone maleate were bioequivalent.

티로파 정(염산티로프라미드 100 mg) 에 대한 안티모딕정의 생물학적 동등성

곽손혁,구선회,린팜두안,강종성,황성주 충남대학교 약학대학 의약품개발연구소 2000 藥學論文集 Vol.16 No.-

Bioequivalence of two tiropramide tablets, test drug (Antimodic® tablet: Chong Kun Dang Pharm. Co.) and reference drug (Tiropa® tablet: Dae Woong Pharm. Co.), was evaluated according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty healthy male volunteers were divided randomly into two groups and administered the drug orally at the dose of 100 mg as tiropramide hydrochloride in a 2×2 crossover study. There was a week washout period between administrations. Blood samples were taken at predetermined time intervals for 10 hr and the plasma concentration of tiropramide HCl was determined by a GC/MS method. AUC_0-10hr (area under the plasma concentration-time curve from time zero to 10 hr), C_max (maximum plasma drug concentration) and T_max (time to reach C_max) were estimated from the plasma drug concentration-time data. Analysis of variance (ANOVA) revealed no difference in AUC_(0-10hr), C_max and T_max between two products. The apparent differences of these parameters between two products were less than 20% (i.e., 0.043, 6.430 and 8.929% for AUC_(0-10hr), C_max and T_max, respectively). The powers (1-β) for AUC_(0-10hr) and C_max were over 0.9. Minimal detectable differences (Δ) at α=0.05, 1-β=0.8 were less than 20% (i.e. 15.71 and 12.53% for AUC_(0-10hr) and C_max, respectively). The 90% confidence intervals (δ) for these parameters were also within ±20% (i.e. -9.15≤δ≤9.24 and -0.90≤δ≤13.77 for AUC_(0-10hr) and C_max, respectively). These results satisfied the criteria of KFDA guidelines for bioequivalence, indicating the two tablets of tiropramide were bioequivalent.

프레팔시드정(시사프리드 5 mg)에 대한 시사컨시드정의 생물학적 동등성

곽손혁,구선회,황성주 충남대학교 약학대학 의약품개발연구소 2000 藥學論文集 Vol.16 No.-

Bioequivalence of two cisapride tablets, test drug (Cisaconsid® tablet: Hankook Nelson Pharm Co.) and reference drug (Prepulsid® tablet. Yansen Pharm. Co.), was evaluated according to the guidelines of Korea Food and Drug Administration (KFDA). Eighteen healthy male volunteers were divided randomly into two groups and administered the drug orally at the dose of 10 mg as cisapride in a 2×2 crossover study. There was a week washout period between administrations. Blood samples were taken at predetermined time intervals for 36 hr and the plasma concentration of cisapride was determined by a HPLC method. AUC_(0-36hr) (area under the plasma concentration-time curve from time zero to 36 hr), C_max (maximum plasma drug concentration) and T_max (time to reach C_max) were estimated from the plasma drug concentration-time data. Analysis of variance (ANOVA) revealed no difference in AUC_(0-36hr), C_max and T_max between two products. The apparent differences of these parameters between two products were less than 20% (i.e., 2.23, 7.99 and 3.81% for AUC_(0-36hr), C_max and T_max., respectively). The powers (1-β) for AUC_(0-36hr), C_max and T_max were over 0.9. Minimal detectable differences (Δ) at α=0.10, 1-β=0.8 were less than 20% (i.e. 16.34, 13.81 and 17.99% for AUC_(0-36hr), C_max and T_max, respectively). The 90% confidence intervals (δ) for these parameters were also within ±20% (i.e. -13.21≤δ≤8.75, -17.27≤δ≤1.28 and -l5.93≤δ≤8.24% for AUC_(0-36hr), C_max and T_max, respectively). These results satisfied the criteria of KFDA guidelines for bioequivalence, indicating the two tablets of cisapride were bioequivalent.

용매증발법에 의한 부피바카인 microsphere의 제조 및 평가

곽손혁(Son Hyok Kwak),황성주(Sung Joo Hwang),이병철(Byung Chul Lee) 대한약학회 2000 약학회지 Vol.44 No.6

Various bupivacaine-loaded microspheres were prepared from poly (d,l-lactide) (PLA) or poly (d,l-lactic-co-glycolide) (PLGA) by a solvent evaporation method for the sustained release of drug. PLA and PLGA microspheres were prepared by w/o/w and w/o/o multiple emulsion solvent evaporation, respectively. The effects of process conditions such as emulsification speed, emulsifier type, emulsifier concentration and internal/external phase ratio on the characteristics of microspheres were investigated. The prepared microspheres were characterized for their drug loading, size distribution, surface morphology and release kinetics. Drug loading efficiency was higher in the microspheres prepared by w/o/o multiple emulsion than that by w/o/w multiple emulsion mehtod, because the solubility of bupivacaine HCl was decreased in oil phase compared with water phase. The prepared microspheres had an average diameter between 1 and 2mcm in all conditions of two methods. In morphology studies the PLA microspheres showed an irregular shape and smooth surface, but PLGA microspheres had a spherical shape and smooth surface. The release pattern of the drug from microspheres was evaluated on the basis of the burst effect and the extent of the release after 24h. The in vitro release of bupivacaine HCl from microspheres showed a large initial burst release and 60-80% release within one day in all conditions of two methods. The extents of the burst release against PLA and PLGA microspheres were 30-50% and 50-80% within 20min, respectively. This burst release seems to be due to the smaller size of microspheres and the solubility of drug in water.

케토롤락트로메타민 서방성 펠렛의 약물속도론적 평가

곽손혁(Son Hyok Kwak),황성주(Sung Joo Hwang),장혁,남경완(Kyung Wan Nam),문영걸(Young Girl Moon),이해방(Hai Bang Lee),조선행(Sun Hang Cho),육순홍(Sun Hong Yuk),이한구(Han Koo Lee),정상영(Sang Young Jeong),이영원(Young Won Lee) 한국약제학회 2000 Journal of Pharmaceutical Investigation Vol.30 No.4

To develop a sustained-release preparation containing ketorolac tromethamine, two sustained-release pellet formulations were evaluated with a pharmacokinetic study as compared with a conventional commercial tablets (10 ㎎ Tarasyn^(TM), Roche Korea Ltd.). Two sustained-release formulations were as follows; formulation A was composed of an inner layer containing 75% of drug coated with Eudragit^(TM) RS 100 membrane and an outer layer containing 25% of drug mixed with Eudragit^(TM) NE30D, and formulation B was composed of only an inner layer containing 100% of drug coated with Eudradit^(TM) RS 100 membrane. The dissolution test was performed for two formulations. In case of conventional tablets, 2.5 ㎎ of drug per a dose was administered orally into male Albino rabbit (2.0-2.3 ㎏ of body weight) 3 times at intervals of 4 hours. In case of two sustained formulations, 7.5 ㎎ of drug was administered once orally. Blood samples were withdrawn periodically after the administration, and the blood concentration was determined by HPLC. The conventional tablets showed very high peak-trough fluctuation between administered doses, but two sustained formulations showed less fluctuation. Formulation A with the loading dose showed the time to reach minimum effective concentration (MEC) i.e. the onset time was less than 20 min, while Formulation B had more than 1 hr of the onset time. Formulation A had the more constant plasma level than formulation B. However, formulation B had a time lag, so the plasma level was less than MEC for an initial period of 1 hr. In formulation A, the plasma level was maintained within the therapeutic window (0.3-5 ㎍/㎖) for a long period. Formulation A was thought to be an ideal sustained-release formulation for ketorolac tromethamine oral delivery system.

Box-Wilson 실험계획에 의한 연마용 인산일수소칼슘의 최적 제조조건 추구 및 안정화

이계주,곽손혁,서성수 한국약제학회 1996 Journal of Pharmaceutical Investigation Vol.26 No.3

An abrasive, calcium hydrogen phosphate dihydrate (DCPD), was synthesized in a Box-Wilson experimental design by reactions between phosphoric acid and milk of lime, and calcium chloride and sodium phosphate solutions, and stabilized with TSPP and TMP. The optimum conditions for preparation of DCPD from phosphoric acid with milk of lime were such as: reaction temp.: 51.9℃, conc. of lime: 25.9%, conc. of phosphoric acd: 77.9%, drying temp.; 60.2℃ and final pH: 6.46. The physico-chemical and pharmaceutical properties of DCPD were showed as follows: glycerin absorption value(68㎖/100g), whiteness(99.5%), particle size(10.9nm), pH(7.8), and set test(pass). XRD and SEM of DCPD indicated a monoclinic system crystallographically. N₂ adsorption isotherm curve by BET showed non porous type II form. The micromeritic parameters of DCPD showed that surface area was 3.27∼4.6㎠/g and pore volume, pore area and pore radius were negligible. The rheogram of the toothpaste containing DCPD showed pseudoplastic flow with yield value of 321, and thixotropic behavior forming hysteresis loop. These results meet the requirements as abrasive standard, and sythesized DCPD is expected as a good dental abrasive such as a high quality grade in practice.

Box-Wilson 실험계획에 의한 연마용 인산일수소칼슘의 최적 제조조건 추구 및 안정화

이계주,곽손혁,서성수 충남대학교 약학대학 의약품개발연구소 1996 藥學論文集 Vol.12 No.-

An abrasive, calcium hydrogen phosphate dihydrate (DCPD), was synthesized in a Box-Wilson experimental design by reactions between phosphoric acid and milk of lime, and calcium chloride and sodium phosphate solutions, and stabilized with TSPP and TMP. The optimum conditions for preparation of DCPD from phosphoric acid with milk of lime were such as: reaction temp.: 51.9℃. conc. of lime: 25.9%. conc. of phosphoric acd: 77.9%. drying temp.: 60.2℃ and final pH: 6.46. The physico-chemical and pharmaceutical properties of DCPD were showed as follows: glycerin absorption value(68 ㎖/100g), whiteness(99.5%), particle size(10.9㎚). pH(7.8), and set test(pass). XRD and SEM of DCPD indicated a monoclinic system crystallographically. N_2 adsorption isotherm curve by BET showed non porous type Ⅱ form. The micromeritic parameters of DCPD showed that surface area was 3.27~4.6 ㎠/g and pore volume. pore area and pore radius were negligible. The rheogram of the toothpaste containing DCPD showed pseudoplastic flow with yield value of 321, and thixotropic behavior forming hysteresis loop. These results meet the requirements as abrasive standard, and sythesized DCPD is expected as a good dental abrasive such as a high quality grade in practice.

프레팔시드 정(시사프리드 5 mg)에 대한 시사플 정의 생물학적 동등성

이계주,황성주,우종수,곽손혁,박종우,한정희,장혁,남진경,구선회 한국약제학회 2000 Journal of Pharmaceutical Investigation Vol.30 No.1

Bioequivalence of two cisapride tablets, test drug (Cisaple^ⓡ tablet: Hanmi Pharm Co., Ltd.) and reference drug (Prepulsid^ⓡ tablet: Janssen Pharm. Co., Ltd.), was evaluated according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty two healthy male volunteers were divided randomly into two groups and administered the drug orally at the dose of 10 mg as cisapride in a 2 × 2 crossover study. There was a week washout period between administrations. Blood samples were taken at predetermined time intervals for 36 hr and the plasma concentration of cisapride was determined by a HPLC method. AUC_(0-36hr) (area under the plasma concentration-time curve from time zero to 36 hr), C_(max) (maximum plasma drug concentration) and T_(max) (time to reach C_(max)) were estimated from the plasma drug concentrationtime data. Analysis of variance (ANOVA) revealed no difference in AUC-(0-36hr), C_(max) and T_(max) between two products. The apparent differences of these parameters between two products were less than 20% (i.e., 5.38, 6.17 and 0.00% for AUC_(0-36hr), C_(max) and T_(max), respectively). The powers (1-β) for AUC_(0-36hr), C_(max) and T_(max) were over 0.9. Minimal detectable differences (△) at α=0.05, 1-β=0.8 were less than 20% (i.e. 17.67, 14.84 and 19.72% for AUC_(0-36hr), C_(max) and T_(max), respectively). The 90% confidence intervals (δ) for these parameters were also within ±20% (i.e. -4.97 ≤ δ ≤ 15.73, -2.53 ≤ δ ≤ 14.86 and -11.55 ≤ δ ≤ 11.55 for AUC_(0-36hr), C_(max) and T_(max), respectively). These results satisfied the criteria of KFDA guidelines for bioequivalence, indicating the two tablets of cisapride were bioequivalent.

경구용 백신수송체용 GFP 함유 마이크로스피어의 제조 및 평가

장혁(Ge Jiang),박종필(Jong Pil Park),곽손혁(Son Hyok Kwak),황성주(Sung Joo Hwang),맹필재(Pil Jae Maeng) 한국약제학회 2000 Journal of Pharmaceutical Investigation Vol.30 No.4

In order to design the oral vaccine delivery system, we prepared the alginate microspheres containing GFP (green fluorescent protein) as a model drug by spray method. To optimize the preparation conditions of microspheres, we investigated the effects of various parameters including nozzle pressure, nozzle opening angle, and concentrations of sodium alginate and calcium chloride. The prepared microspheres were evaluated by measuring their sizes, loading efficiency, and morphology. The particle size of microspheres was affected by the concentration of sodium alginate and calcium chloride, nozzle pressure, and nozzle opening angle. As the concentration of sodium alginate increased, GFP loading efficiency and particles size of microsphere also increased. However, it was observed to be difficult to spray the sodium alginate solution with concentration greater than 1.5% (w/v), due to high viscosity. The pressure over 3 kgf/㎠ didn`t affect the size of particles. As a result, the spraying method enabled us to prepare microspheres for oral vaccine delivery system. In this study, microspheres prepared with 1% (w/v) sodium alginate had greater loading efficiency and better spherical shape.