아세클로페낙 연질캡슬(클란자 에스 연질캡슬)의 개발

용철순,이경희,최진석,박병주,정세현,김용일,박상만,배명수,김귀자,김영식,유창훈,강성룡,유봉규,이종달,최한곤 한국약제학회 2004 Journal of Pharmaceutical Investigation Vol.34 No.1

To develop and aceclofenac soft capsule, four preparations with various solubilizers were prepared and their dissolution test was carried out. Among four preparations tested, a preparation with ethanolamine was selected a formula of aceclofenac soft capsule (Clanza S^(™), since it showed the fastest dissolution rate. Bioequivalence of aceclofenac tablet, Airtal^(™)(Dae-Woong Pharmaceutical Co., Ltd.) and aceclofenac soft capsule, Clanza S^(™)(Korea United Pharmaceutical Co., Ltd.) was evaluated according to the guideline of KFDA. Fourteen normal male volunteers (age 20-25 years old) were divided into two groups and a randomized 2×2 cross-over study was employed. After oral administration of one tablet or capsule containing 100 ㎎ of aceclofenac, blood ws taken at predetermined time intervals and the concentration of aceclofenac in plasma wa determined with an HPLC method under UV detector. The pharmacokinetic parameters (C_(max), T_(max) and AUC_(t)) were calculated and ANOVA was utilized for the statistical analysis of parameters using logarithmically transformed AUC_(t), C_(max) and T_(max) between Airtal tablet and Clanza soft capsule were 2.89%, 0.18% and 43.0%, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.250(e.g.log(0.81) - log(1.23) and log(0.89) - log(1.14)) for AUC_(t) and C_(max), respectively. Thus, the criteria of the KDFA guidelines for the equivalence was satisfied, indicating that Clanza S^(™) soft capsule is bioequivalent to Airtal^(™) tablet.

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.

폴록사머를 이용한 디클로페낙 고형 좌제의 개발

용철순,오유경,김정애,김용일,박상만,양준호,이종달,최한곤 한국약제학회 2004 Journal of Pharmaceutical Investigation Vol.34 No.2

To develop a poloxamer-based solid suppository with poloxamer mixtures, the melting points of various formulations composed of P 124 and P 188 were investigated. To investigate the effect of poloxamer to the dissolution and dissolution mechanism of diclofenac sodium from the suppository the dissolution of diclofenac sodium delivered by the poloxamer-based suppository was performed. Furthermore, to investigate the mucoadhesive property of the poloxamer-based solid suppository, the identification test in the rectum was carried out after its rectal administration in rats. The poloxamer mixtures composed of P 124 and P 188 were homogeneous. Very small amounts of P 188 affected the melting points of poloxamer mixtures. In particular, the poloxamer mixture [P 124/P 188 (97/3%)] with the melting point of about 32℃ was a solid form at room temperature and instantly melted at physiological temperature. Furthermore, very small amounts of P 188 in the poloxamer-based suppository hardly affected the dissolution rates of diclofenac sodium from the suppository. Dissolution mechanism analysis showed the dissolution of diclofenac sodium was proportional to the time. At 4 h after administration, the blue color of poloxamer-based suppository [diclofenac sodium/poloxamer mixture (2.5/97.5%)] with the P 124/P 188 ratio of (97/3%) and blue lake in the rectum was faded. However, the position of suppository in the rectum did not significantly change with time. Thus, it retained in the rectum for at least 4 h. Our results indicated that the poloxamer-based solid suppository with P 124 and P 188 would be a candidate of rectal dosage from for diclofenac sodium.

헬리코박터 파이로리 균 진단용 ^13C-요소 캅셀의 개발

용철순,김용일,김지만,강성훈,권기철,이종달,김종국,사홍기,최한곤 한국약제학회 2002 Journal of Pharmaceutical Investigation Vol.32 No.1

The purpose of this study was to develop a new ^13C-urea- containing capsule for diagnosis of H. pylori. The urea-containing capsules were prepared with various diluents such as polyethylene glycol (PEG), microcrystalline cellulose, sodium lauryl sulfate and citric acid. The dissolution test, ^13C-urea breath test and stability test were then performed on the capsules. Microcrystalline cellulose and sodium lauryl sulfate retarded the initial dissolution rates of urea. However, PEG increased the initial dissolution rates of urea. Furthermore, two formulae composed of PEG, [^13C-urea/PEG (38/1.9 mg/cap)] and [^13C-urea/PEG/citric acid (38/1.9/1.9 mg/cap)] had the maximum DOB value, about 16 at 20 mim, while the formula composed of only 38 mg ^13C-urea had the maximum DOB value at 30 min. The results indicated that PEG improved the sensitivity of ^13C-urea in the human volunteers. The capsule [^13C-urea/PEG (38/1.9 mg/cap)] was stable for at least six months in 25 and 37℃. Thus, a PEG-containing capsule, [^13C-urea/PEG (38/1.9 mg/cap)] would be a more economical, sensitive and stable preparation for diagnosis of H. pylori.

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.

신부전환자에 있어서의 혈청이온화된 칼슘의 측정

박한철,엄대용,이상돈 중앙대학교 의과대학 의과학연구소 1984 中央醫大誌 Vol.9 No.1

1. With glass microelectrode technique specific for calcium ion, measurements were made for serum ionized calcium. The calibration curve was linear for pCa(2-4) and the tests were reproducible. 2. For five persons each with normal health and with uremia, serum creatinine above 10㎎/㎗, ionized calcium, total calcium, total protein, albumin, and inorganic phosphate were measured in the sera. The results are as following: 1) There were significant differences in serum phosphate and ionized calcium levels between healthy group and uremic patients. The differences were not significant in total calcium, total protein, and albumin contents. 2) The values of ionized calcium, total calcium, total protein and albumin were scattered, but individually some with uremia had lower values. 3. Preliminary tests for ionized calcium assay gave the experience that the ways of collecting and storing samples would alter the data significantly. 4. It is, therefore, felt that further studies on simplification of the sample handing before the measurement of ionized calcium is desirable.

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.

프레탈정 (실로스타졸 100mg)에 대한 실로스탄정 (한국유나이티드 제약)의 생물학적 동등성

용철순,이경희,최진석,박병주,정세현,김용일,박상만,유봉규,이종달,최한곤 한국병원약사회 2003 병원약사회지 Vol.20 No.2

Bioequivalence of one cilostazol tablets, the Pletaal^(R)(Korea Otsuka Pharmaceutical Co., Ltd.) and Cilostan^(R)(Korea united Pharmaceutical Co., Ltd.), was evaluated according to the guideline of KFDA. Sixteen normal male volunteers(age 20~30 years old)were divided into two groups and a randomized 2×2 cross-over study was employed. After one tablet containing 100㎎ 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 parameter. The results showed that the differences in C_(max), T_(max) and AUC_(t) between one tablet were 16.08%, 18.88% and 17.57%, respectively. The powers (1-β) for C_(max), T_(max) and AUC_(t) were 85.03%, 83.92% and 80.12%, 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 Cilostan^(R) tablet is bioequivalent to Pletaal^(R) tablet.

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.

근린약국에서 산제로 조제된 아테놀올정의 안정성

용철순,최한곤,이종달,유봉규 한국약제학회 2004 Journal of Pharmaceutical Investigation Vol.34 No.4

Prescription filling in powder form is performed in community pharmacy practice to adjust dose for children and patients who cannot swallow whole tablet. However, there are few reports regarding the stability of the active ingredient and possible microbial growth after the medication is dispensed to powder form. This study examined the stability of atenolol, an antihypertensive agent, and microbial growth in the unit dose pouches dispensed at twenty-one community pharmacies located in Taegu area. Randomly chosen first unit dose pouch contained 77.4% of the prescribed dose of the drug and there were only four community pharmacies that dispensed the drug within 10% deviation from the dose prescribed by physician. Surprisingly, there were three community pharmacies that dispensed the drug with greater than 40% deviation, which may pose a major concern regarding the efficacy and safety of the drug prescribed for the treatment of hypertension. Atenolol content during a month did not indicate significant change, showing 5.4%, 4.3%, and 3.3% of decrease in 50%, 80%, and 90% relative humidity conditions, respectively. Microbiological examination during a month showed less than 0.5 microorganism in high power field (hpf) in all the relative humidity conditions tested. Based on this study, pharmacy practice in community pharmacy needs to be rigorously regulated to ensure that the dose of the prescribed drug is properly incorporated into the unit dose pouch dispensed as powder form.