테르페나딘-β-시클로덱스트린 포접화합물의 제조방법 및 물리화학적 특성

최한곤,유제만,윤성준 한국약제학회 1997 Journal of Pharmaceutical Investigation Vol.27 No.3

Terfenadine, antihistaminic drug, is poorly soluble in water. The purpose of this study is to investigate the possibility of using terfenadine-β-cyclodextrin inclusion compound, instead of terfenadine, as the active substance of solid dosage form by improving the solubility, dissolution and anti-histaminic activity of terfenadine. The solubility and binding characteristics of terfenadine-β-cyclodextrin complex in pH 1.2∼6.8 were investigated. Furthermore, the preparing method of terfenadine-β-cyclodextrin inclusion compound was setting up and its physico-chemical characteristics such as DSC curve, solubility, dissolution and anti-histaminic activity were investigated. In conclusion, the solubility of terfenadine was increasing by β-cyclodextrin and with the decreasing pH. Terfenadine-β-cyclodextrin inclusion compound, whose yield is almost 100%, was prepared by neutralization method. This inclusion compound was 200-times as soluble as terfenadine in pH 1.2-6.8. In addition, it had the faster dissolution and anti-histaminic activity than terfenadine. Therefore. it is used to the active substance of solid dosage form such as tablet and capsule in stead of terfenadine.

Terfenadine-pseudoephedrine HCI의 이중정 및 유핵정의 비교 용출시험

최한곤 한국약제학회 1997 Journal of Pharmaceutical Investigation Vol.27 No.3

The present sustained-release terfenadine-pseudoephedrine HCl dosage form was the core tablet composed of outer (fast-release) layer containing 60㎎ of terfenadine and 10㎎ of pseudoephedrine HCl, and inner (sustained-release) layer containing 110㎎ of pseudoephedrine HCl. The purpose of this study was to investigate the possibility of formulating the terfenadine-pseudoephedrine HCl double-layered tablet which was bioequivalent to the core tablet. Its sustained-release and fast-release layer were formulated with disintegrating agents and polymers, respectively, varying with their kinds and amounts. The comparative dissolution test of double-layered and core tablet was carried out at pH 1.2, 4.0 and 6.8, leading to select composite of double-layered tablet whose dissolution pattern was similar to that of core tablet. It was composed of fast-release layer containing 60㎎ of terfenadine, 10㎎ of pseudoephedrine HCl, sodium bicarbonate, microcrystalline cellulose and sodium starch glycolate, and sustained-release layer containing 110㎎ of pseudoephedrine HCl and ethylcellulose/hydroxypropyl methylcellulose) (110/30㎎/tablet).

PGE₁-ethyl Ester함유 발기부전 치료용 요도주입 액제의 제조 및 평가

최한곤,유봉규,이종달,김정애,권태협,우종수,용철순,Choi, Han-Gon,Yoo, Bon-Kyu,Rhee, Jong-Dal,Kim, Jung-Ae,Kwon, Tae-Hyub,Woo, Jong-Soo,Yong, Chul-Soon 한국약제학회 2006 Journal of Pharmaceutical Investigation Vol.36 No.4

[ $PGE_1$ ]-ethyl ester intraurethral solutions were prepared in ethanol/propylene glycol mixture with penetration enhancer and viscosity-enhancing agent. The stability of $PGE_1$-ethyl ester in intraurethral solution was investigated at various temperature. Simultaneous determination of $PGE_1$-ethyl ester and $PGE_1$ was performed using a validated HPLC technique. In pentobarbital anesthetized cats, increase in intracavernous pressure(ICP), increase in penile length and duration of erectile response were determined after intraurethral application of $PGE_1$-ethyl ester solutions. $PGE_1$-ethyl ester solutions, when instilled into the eyes of rabbits, produces no noticeable irritation, or slight transient conjunctival irritation. From these results, ocular irritation of this solutions was judged as practically non-irritating. The stability study indicates that the therapeutically effective content in solution is well maintained for 46 weeks or longer when they are stored at $4^{\circ}C$. After intraurethral application of $PGE_1$-ethyl ester, ICP was increased and penile erection was induced. $PGE_1$-ethyl ester intraurethral solutions for erectile dysfunction could be developed and evaluated by employing feline erection model.

흰쥐에서 다시마 식이가 메트폴민의 체내동태 및 당 흡수에 미치는 영향

최한곤,장보현,이종달,김정애,유봉규,용철순 한국약제학회 2003 Journal of Pharmaceutical Investigation Vol.33 No.3

Drug interactions with food, on occasion, led to serious nutritional and functional changes in the body as well as alterations of pharmacological effect. It, therefore, should be necessary to take drug interactions with food into consideration for effective and safe therapeutics. Diabetes mellitus is a heterogeneous group of disorders characterized by abnormal glucose homeostasis, resulting in hyperglycemia, and is associated with increased risk of microvascular, macrovascular, and neuropathic complications. However, the precise mechanism of diabetes mellitus remins unclear. Three basic objectives in the care of diabetic patients are maintaining optimal nutrition, avoiding hypo-or hyperglycemia and preventing complications. Laminaria japonica is a brown macroalgae which can be used as a functional diet due to high content of diatery fiber. the purpose of this study was to investigate the effect of Laminaria japonica diet on the pharmacokinetics of metformin which are frequently used in the treatment of diabetes. Diabetic rats induced by strep-tozotocin were employed in this study. Blood concentrations of oral hypoglycemic agent, metformin, were measured by HPLC and resultant pharmacokinetic parameters were calculated by RSTRIP. The mechanisms of drug interaction with food were evaluated on the basis of pharmacokinetic parameters such as k_(a), t_(1/2), C_(max), t_(max), and AUC, C_(max), and k_(a), and increase in t_(max), compared to those with normal diet. This oral glucose test showed that Laminaria japonica diet could lower blood glucose level probably through either inhibiting the activity of disaccharidases, intestinal digestive enzymes, or delaying the absorption of glucose. More studies should be followed to fully understand pharmacokinetic changes of metformin caused by ong-term Laminaria japonica diet.

클렌부테롤의 피부투과에 미치는 경피흡수촉진제의 영향

최한곤,이종달,유봉규,용철순 한국약제학회 2003 Journal of Pharmaceutical Investigation Vol.33 No.1

Clenbuterol, a selective β_2-adrenergic receptor stimulant, has been introduced as a potent bronchodilator for patients with bronchial asthma, chronic obstructive bronchial disease, chronic bronchitis and pulmonary emphysema. The percutaneous permeation of clenbuterol was investigate in hairless mouse skin after application of 50/50 buffer(pH 10)/propylene glycol solvent mixture. The enhancing effects of various penetration enhancers such as terpenes, non-ionic surfactants, pyrrolidones, fatty acids and some other enhancers on the permeation of clenbuterol were evaluated using Franz diffusion cell. Among terpenes studied, 1,8-cineole was the most effective enhancer, which increase the permeability of clenbuterol approximately 39.33-fold compared with the control without penetration enhancer, followed by menthone with enhancement ratio of 23.57. Nonionic surfactants did not have significant enhancing effects. N-Lauryl-2-pyrrolidone increased the permeability of clenbuterol approximately 4.51-fold compared with the control. Lauric acid increased the permeability of clenbuterol approximately 35.57-fold with decreasing the lag time from 2.64 to 0.52 hr. Oleic acid, linoleic acid, the permeability of clenbuterol 9.24-fold compared with that without enhancer.

아세트아미노펜 액상좌제의 물리화학적 특성에 미치는 첨가제의 영향

최한곤 강원대학교 종합약학연구소 1999 약학연구 Vol.11 No.-

프레탈^(R)정(실로스타졸 50mg)에 대한 실로졸^(R)정의 생물학적 동등성

최한곤,권기철,이승호,김학미,박병주,유봉규,이종달,이경희,하정희,우종수,박인숙,최진석,용철순 한국병원약사회 2003 병원약사회지 Vol.20 No.1

Bioequivalence of two cilostazol tablets, the Pletaal^(R)(Korea Otsuka Pharmaceutical Co., Ltd.) and the Cilozol^(R)(Hanmi Pharmaceutical Co., Ltd.), was evaluated according to the guideline of KFDA, Sixteen normal male volunteers(age 20~29 years old) were divided into two groups and a randomized 22 cross-over study was employed. After two tablets containing 50㎎ of cilostazol were orally administered. blood was taken at predetermined time intervals and the concentration of cilostazol in plasma was determined with an HPLC method using UV detector. The pharmacokinetic parameters(C_(max), T_(max) and AUC_(t)) were calculated and ANOVA was utilized for the statistical analysis of parameters. The results showed that the differences in C_(max), T_(max) and AUC_(t) between two tablets were 4.99%, 1.74% and 7.68%, respectively. The powers(1-β) for C_(max), T_(max) and AUC_(t) were83.92%, 80.12% and 85.03%, respectively. Detectable differences(Δ) and confidence intervals were all less than 20%, and confidence interval of all the parameters were also less than 20% at the significance level(α) of 0.05. All of these parameters met the criteria of KFDA for bioequivalence, indicating that Cilozol^(R) tablet is bioequivalent to Pletaal^(R) tablet.

클렌부테롤 경피흡수제제의 개발

최한곤,권기철,정시영,이종달,용철순 영남대학교 약품개발연구소 2001 영남대학교 약품개발연구소 연구업적집 Vol.11 No.-

The advantages of transdermal administration are avoiding hepatic first pass effect, minimizing inter- and intra-patient variation, maintaining steady-state plasma level to provide long-term therapy from a single dose, and allowing a rapid termination of drug input. Clenbuterol, a selective B_(2)-adrenergic receptor stimulant, has been introduced as a polent bronchodilator for patients with bronchial asthma, asthma, chronic obstructive bronchial disease. For the development of transdennal systems containing clenbuterol, two limiting factors ? long lag time and low flux - must be overcome. In this studym we altempted to select optimal formulation for preparation of clenbuterol patch using hairless mouse skin and flow-through diffusion cell. The flux of clenbuterol increased as the percent of clenbuterol dose dependently in the concentration range of 5-15%. Based on this result, we fixed the concentration of clenbuterol as 15%. The effect of various penetration enhancers on percutaneous absorption of clenbuterol through hairless mouse skin was investigated. Labrafil was the most effective enhancer, which increased the permeability of clenbuterol approximately 4-fold compared with the control without penetration enhancer. Optimal enhancer concentration was 3%. The effect of various adhesives on penetration of elenbuterol was also investigated. Among the adhesives studied, MA-31 was the most effective adhesive. Futhermore, the clenbuterol patch composed of 15% clenbuterol. 3% Labrafil and 82% MA-31, which gave most excellent penetration of drug in in vitro penetration study, maintained therapeutic plasma levelsin in vivo study using S.D. rats. These studies demonstrated a good feasibility of clenbuterol administration through the intact skin using a transdermal patch, and show a possibility of the development of clenbuterol patches.

다시마 식이가 흰쥐에서 글리피지드의 체내동태에 미치는 영향

최한곤,장보현,이종달,유봉규,용철순 한국약제학회 2003 Journal of Pharmaceutical Investigation Vol.33 No.2

Drug interactions with food, on occasion, lead to serious nutritional and functional changes in the body as well as alternations of pharmacological effect. It, therefore, should be necessary to take drug interactions with food into consideration for effective and safe therapeutics. Diabetes mellitus is a heterogeneous group of disorders characterized by abnormal glucose homeostasis, resulting in hyperglycemia, and is associated with increase risk of micovascular, macrovascurlar, and neuropathic complications. However, the precise mechanixm of diabetes mellitus remains unclear. Three basic objectives in the care of diabetic patients are maintaining optimal nutrition, avoiding hypo- or hyperglycemia and preventing complications. The purpose of this study was to investigate the effect of Laminaria japonica diet on the absorption, distribution, metabolism and excretion of glipizide which are frequently used in the treatment of diabetes. Diabetic rats induced by streptozotocin were employed in this study. Blood concentrations of oral hypoglycemic agents were measured by HPLC and resultant pharmacokinetic parameters were calculated by RSTRIP. The mechanisms of drug interaction with food were evaluated on the basis of pharmacokinetic parameters such as k_a, t_1/2, C_max, t_max, and AUC. Administration of glipzide in normal rats treated with Laminaria japonica diet showed significant increase in AUC, k_a, t_1/2, t_max and decrease in C_max, compared to those without Laminaria japonica diet. This might result from adsorption of glipizide on components of Laminaria japonica, causing delayed absorption. Administration of glipizide in diabetic rats treated with Laminaria japonica diet showed significant increase in t_1/2 and t_max, and decrease in C_max, compared to those without Laminaria japonica diet. This might also result from adsorption of glipizide on components of Laminaria japonica, causing delayed absorption and flattened blood concentration of glipizide. The oral glucose test showed that Laminaria japonica diet could lower blood glucose level probably through either inhibiting the activity of disaccharidases, intestinal digestive enzymes, or delaying the absorption of glucose. More studies should be followed to fully understand pharmacokinetic changes of glipizide caused by long-term Laminaria japonica diet.

액상좌제 기제의 물리화학적 성질에 미치는 첨가제의 영향

최한곤(H . G . Choi),이미경(M . K . Lee),김문희(M . H . Kim),김종국(C . K . Kim) 한국약제학회 1999 한국약제학회 총회 및 학술대회 요지집 Vol.- No.29

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