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.

폴록사머 188 및 멘톨에 의한 이부프로펜의 용해도 증가

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

To enhance the solubility of poorly water-soluble ibuprofen with poloxamer and menthol, the effects of menthol and poloxamer 188 on the aqueous solubility of ibuprofen were investigate. In the absence and presence of additives such as ethanol and poloxamer 188, the solubility of ibuprofen increased until the ratio of menthol to ibuprofen increased from 0:10 to 4:6 followed by and abrupt decrease in solubility above the ratio of 4:6, indicating tat 4 parts of ibuprofen formed eutetic mixture with 6 parts of menthol. In the presence of poloxamer, the solutions with the same ratio showed abrupt increase in the solubility of ibuprofen . Furthermore, in the presence of poloxamer, the solution with ratio of 4:6 showed more than 2.5- and 6-fold increase in the solubility of ibuprofen compared with that without additives and that without menthol, respectively. The solution with menthol/ibuprofen ratio of 1:9 and higher than 15% poloxamer 188 showed the maximum solubility of ibuprofen, 1.2㎎/ml. Thus, menthol gave the greatly enhanced solubility of ibuprofen with poloxamer 188.

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.

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.

헬리코박터 파이로리 균 진단용 ^13C-요소 캅셀의 개발

용철순,김용일,김지만,강성훈,권기철,이종달,김종국,사홍기,최한곤 영남대학교 약품개발연구소 2002 영남대학교 약품개발연구소 연구업적집 Vol.11 No.-

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), microcrystaline 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 (38/1.9/1.9 mg/cap)] had the maximum DOB value. about 16 at 20 min, 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 perparation for diagnosis of H. pylori.

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.

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.

경피흡수에 영향을 미치는 인자

용철순,이종달,최한곤 영남대학교 약품개발연구소 2000 영남대학교 약품개발연구소 연구업적집 Vol.10 No.-

Transdermal drug delivey systems(TDDS) are known to have various adavantages over conventional dosage forms, such as simple dosage, prolonged and controlled action of drugs, avoidance of hepatic first-pass effect, and greater improved patient compliance. One of the main shortcomings of TDDS, however, is poor percutaneous absorption. Many biological and physicochemical factors influencing percutaneous absorption is described together with the corresponding experimental results and practical examples.

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.

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.