살리실산 유사체류의 물성이 우혈청 알부민 결합에 미치는 영향

용철순 한국약제학회 1993 Journal of Pharmaceutical Investigation Vol.23 No.3

The protein binding of salicylate analogs has been investigated by equilibrium dialysis. A series of binding experiments were performed in order to elucidate the effects of physicochemical properties of salicylate analogs on the binding with bovine serum albumin. Attempts to correlate affinity constants with capacity factor, steric factor and Hammett σ values suggested hydrophobic forces to be involved in the binding of salicylate analogs. Steric factor contributes to binding process partly, whereas electronic interaction appears to be insignificant.

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.

아테놀 근린약국에서 산제로 조제된 올정의 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.

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.

덱사메타손 21-아세테이트를 함유한 콘드로이틴 설페이트/젤라틴 마이크로스피어의 제조 및 평가

용철순,김영주,오두만 영남대학교 약품개발연구소 1997 영남대학교 약품개발연구소 연구업적집 Vol.7 No.-

Chondroitin sulfate/gelatin microspheres containing dexamethasone 21-acetate were prepared by complex coacervation method and their release patterns were examined in vitro. Microspheres prepared with a small amount of crosslinking agent had smooth surface and few pores, but those with a large amount of crosslinking agent were more porous and less spherical. In vitro release patterns were varied by changing polymer/drug weight ratio and amount of crosslinking agent. The release rate of dexamethasone 21-acetate in the presence of collagenase was faster than that in the absence of collagenase. Anti-inflammatory effect of dexamethasone 21-acetate microspheres was more efficient than that of dexamethasone 21-acetate solution in carrageenan-induced arthritis in the rat. On the basis of the above results. we might expect the degradation and drug release rate of these microspheres to be regulated by the degree of crosslinking and the level of enzymes. In patients with sever rheumatoid arthritis who have high concentration of collagenase, more drug would be released from the microspheres. An intra-articular injection therapy of rheumatoid arthritis with desired release kinetics could be developed to enhance patient compliance and therapeutic index.

신제제기술과 제품현황 : 주사제 및 점안제의 신제제 개발 현황

용철순 한국약제학회 1995 제제기술워크샵 Vol.- No.7

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.

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.

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.

생물공학 물질의 제제화 기술 동향 / 단백성 약물의 최근동향

용철순 한국약제학회 1998 제제기술워크샵 Vol.- No.9