뉴로메드정(옥시라세탐 800㎎)에 대한 뉴라세탐정의 생물학적동등성

최성업,김종석,윤미경,김정일,박석,한상범,이재휘,최영욱 한국약제학회 2004 Journal of Pharmaceutical Investigation Vol.34 No.3

The purpose of the present study was designed to evaluate the bioequivalence of two oxiracetam tablets, Neuromed tablet (Korea Drug Co., reference drug) and Neuracetam tablet (Sam Jin Pharmaceutical Co., test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Release of oxiracetam from the tablet in vitro was tested using KP Ⅷ Apparatus Ⅱ method with various dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty-four healthy volunteers, 23.7 ± 2.4 year in age and 68.9 ± 6.2 ㎏ in body weight, were divided into two groups and a randomized 2×2 cross-over study was performed. After oral administration of a tablet containing 800 ㎎ of oxiracetam, blood samples were taken at predetermined time intervals and concentrations of oxiracetam in plasma were determined using HPLC-MS-MS. The dissolution profiles of two formulations were very similar at all dissolution media. In addition, pharmacokinetic parameters such as AUCt, C_(max) and T_(max) were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed AUC, and C_(max), untransformed T_(max). The results showed that the differences between two formulations based on the reference drug were 0.42%, 0.45% and -12.58% for AUCt, C_(max) and T_(max), respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals for the log transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., log0.94 ~ log1.06 and log 0.90 - log 1.07 for AUCt and C_(max), respectively), indicating that Neuracetam tablet is bioequivalent to Neuromed tablet. The major pharmacokinetic parameters, AUCt, and C_(max), met the criteria set by KFDA for bioequivalence indicating that Neuracetam tablet is bioequivalent to Neuromed tablet.

고형지질나노입자를 이용한 파클리탁셀의 주사제 설계

최성업,김선규,이정민,최영욱 한국약제학회 2003 Journal of Pharmaceutical Investigation Vol.33 No.4

Many studies have been attempted to overcome the problems of paclitaxel related to the extremely low aqueous solubility of paclitaxel and the unexpected side-effects caused by Cremophor® EL in a commerical paclitaxel formulation. Taxol®. In order to formulate a new delivery system suitable for intravenous administration without toxic excipients, in this study, paclitaxel was incorporated into solid lipid nanoparticles (Px-SLN) by hot homogenization technique using a microfluidizer. Particle size and zeta potential were measured by a Zetasizer. In vitro drug release experiment was performed by a dialysis diffusion method. Each Px-SLN or Taxol® was intravenously administered to the male Sprague-Dawley rats at a dose of 5㎎/㎏ as paclitaxel. Blood samples were deproteinated with acetonitrile and assayed for paclitaxel by the validated HPLC/MS/MS method. Mean particle size and zeta potential were measured as 72.1 nm(<Polydispersity 0.3) and -41.5 mV, respectively. The content of paclitaxel in SLN was 1.42 ㎎/ml and the drug loading efficiency was 71.2±4.3%. The AUC_(t) of Px-SLN was 3.4-fold greater than that of Taxol^(?). The Px-SLN might be a promising candidate for an alternative formulation for the parenteral delivery of paclitaxel.

국내산 중하(Metapenaeus joyneri) 내 주알레르겐 규명 : 가열 및 소화액에 의한 변화

윤성호,김현아,김현미,최정희,서창희,남동호,김윤근,민경업,박해심 대한알레르기학회 2004 천식 및 알레르기 Vol.24 No.2

섬유강화 고분자 복합판의 기계적 성질에 미치는 섬유길이와 섬유함유율의 영향

이상동,김혁,허업,최종대,이동기 조선대학교 에너지.자원신기술연구소 1997 에너지·자원신기술연구소 논문지 Vol.19 No.2

This paper describes effect of chopped strand length fiber content and moisture absorption on mechanical properties of fiber-reinforced polymeric composites. It was extrusion compounded long fiber-reinforced polypropylene containing 20, 30 and 50 percent and short fiber-reinforced ABS and PAS containing 30 percent b37 the weight of glass fiber. The test methods of ASTM D638, D3410-87 and D79OM are applied for tensile, compressive and bending tests respectively. The results show that, in the case of 0.2% moisture absorption, the residual strength decreases dramatically.

2×2 교차설계에 의한 생물학적 동등성 시험에서 결측치가 있을 때의 통계적 해석 방법

박상규,이재영,최성업,윤미경,이재휘,최영욱 한국약제학회 2004 Journal of Pharmaceutical Investigation Vol.34 No.5

Statistical interpretations in a bioequivalence trial are considered and studied when the missing observations occurred in 2 × 2 crossover experiment. Patel (1985) suggested the approximate test procedures for carryover effect and drug effect in 2 × 2 crossover design when some of data are missing in the second period. A modified Patel method is newly pro-posed to the bioequivalence trial and it is compared with the current method through the simulation study.

수성미세채널을 형성하는 서방성 매트릭스 장용정을 이용한 탐스로신의 방출제어

이기봉,최성업,전홍렬,이봉상,김현일,이재휘,최영욱 한국약제학회 2004 Journal of Pharmaceutical Investigation Vol.34 No.6

Tamsulosin has been frequently used for the treatment of benign prostatic hyperplasia. To avoid dose-dependent side effects of tamsulosin upon oral administration, the development of sustained-release delivery system is required, that can maintain therapeutic drug levels for a longer period of time. The aim of this study was therefore to formulate sustained-release tamsulosin matrix tablets and assess their formulation variables. We designed enteric coated sustained-release tamsulosin matrices to fulfill above statement. Aqueous microchannels in the enteric film need to be formed in order to obtain tamsulosin release even in an acidic environment such as gastric region. In the sustained-release tamsulosin matrix, low viscosity hydroxypropylmethylcellulose was used as a rate controller. Povidone K30 was also added to the matrices to facilitate water uptake so that a decrease in the release rate of tamsulosin as time elapses was prevented, possibly leading to pseudo zero-order release of the drug. The matrices were enteric-coated with hydroxypropylmethylcellulose phthalate (HPMCP), along with povidone K30 as an aqueous microchannel former. With the aqueous microchannels formed within the enteric film, tamsulosin could be released in an acidic condition. The release of tamsulosin decreased with increasing thickness of HPMCP membrane while the release rates of tamsulosin from those having different HPMCP thickness in pH 7.2 aqueous media were not considerably different, indicating that the enteric film was promptly dissolved at pH 7.2. These results clearly suggest that the sustained-release oral delivery system for tamsulosin could be designed with satisfying drug release profile approved by the KFDA.

현탁된 고형지질나노입자 내로 친수성 약물의 봉입률을 증대시키기 위한 w/o/w 에멀션 가온용융유화법의 평가

이병무,최성업,이재휘,최영욱 한국약제학회 2005 Journal of Pharmaceutical Investigation Vol.35 No.1

Recently increasing attention has been focused on solid lipid nanoparticles (SLN) as a parenteral drug carrier due to its numerous advantages that can come from both polymeric particle and fat emulsions, together with the possibility of controlled release and increasing drug stability. Lipophilic drugs such as paclitaxel. cyclosporin A, and all-trans retinoic acid have been successfully entrapped in SLN but the incorporation of hydrophilic drugs in SLN is very limited because of their very low affinity to the lipid. Therefore, as a new approach to improve the loading of hydrophilic drugs, a w/o/w emulsion technique has been developed. The primary objective of the current study was to improve the loading efficiency of a model hydrophilic drug, glycine (Log P = -3.44) into SLN. The proposed preparation process is as follows: A heated aqueous phase consisting of 0.1 ml of glycine solution in water (100 mg/ml), and poloxamer 188 (5 mg) were then added to a molten oil phase containing precirol (100 mg) and lecithin (5 mg). This mixture was dispersed by sonicator, leading to a w/o emulsion. A double emulsion (w/o/w) was formed after the addition of 2% poloxamer solution to the above dispersed system. After cooling the double emulsion, solid lipid nanosuspensions were successfully formed. The lipid nanoparticles had the mean particle size of 441.25 nm, and the average zeta potential of -20.98 mV. The drug loading efficiency was measured to be 8.54% and the drug loading amount was measured to be 0.92%. The w/o/w emulsion method showed an increased loading efficiency compared to conventional o/w emulsion method.

골뱅이(Buccinum Undatum) 알레르기 : 감작률과 다른 음식물 항원과의 연관성 Sensitization rate and its relationship with other food allergens

이재영,윤성호,서유진,최정희,서창희,남동호,김윤근,민경업,박해심 대한천식 및 알레르기학회 2004 천식 및 알레르기 Vol.24 No.1

Background : The common whelk (Buccinum undatum) is one of the largest and most common snails in the North Atlantic. In Korea and Japan, common whelk is a popular eatable shellfish. Although shellfish has been known as the one of the most common causes of food allergy, there has been no published report on allergenecity and clinical significance of this sea snail. In this study, we determined the sensitization rate to common whelk and its relationship with other food allergens in allergy patients. Method : We carried out the skin prick test (SPT) with commonly consumed food stuffs in Korea including common whelk in 1700 patients over 1 year. The specific IgE to common whelk were detected by enzyme-linked immunosorbent assay (ELISA). ELISA inhibition test using sensitized sera was conducted. Results : SPT to common whelk was positive (≥2+) in 83 (4.9%) patients studied. Twenty-four (38.7%) of 62 SPT-positive patients had high serum specific IgE to common whelk. ELISA inhibition test showed significant inhibitions by abalone as well as by common whelk and, minimal inhibition were noted by shrimp. Significant correlation was also noted in specific IgE levels between common whelk and abalone (r=0.58, F<.05). Conclusion : IgE-sensitization rate to common whelk was 4.9% in allergy patients. Further stuides are needed to evaluate the clinical significance of sensitized patients to common whelk, and to confirm a cross reactivity with abalone. (J Asthma Allergy Immunol 24 : 77-84, 2004)

건강한 한국인 성인 남성에서 레보설피리드 제제의 생체이용률

이정민,최성업,김희규,윤미경,김세희,염정록,최영욱 한국약제학회 2003 Journal of Pharmaceutical Investigation Vol.33 No.3

Pharmacokinetics and oral bioavailability of levosulpiride was determined in Korean healthy male volunteers. Thirty subjects received a single oral dose (25 ㎎) of a tablet in randomized 2×2 cross-over design. The plasma concentratons of levosulpiride were measured by HPLC and compared with those reported in the literature. Pharacokinetic parameters for Isomeric^(??) tablet (levosulpiride 25 ㎎) were revealed as follows: AUC _(inf) 737.1±176.9 ng·hr/ml, C_(max) 56.4±20.1 ng/ml, T_(max) 4.2±1.6hr, K_(a) 1.00±1.09 hr^(-1), K_(el) 0.08±0.02 hr^(-1), and t_(1/2) 8.8±1.9 hr. The rate constant of the absorption phase was obtained based on the first-order kinetics. In the aspect of bioavailability, Isomeric^(??) tablet was bioequivalent to the other product (Levopride^(?)tablet) available in the Korean market. Intersubject variations and race differences were shown in comparison with the published date in the literature, even though there ws a linear relationship between dose and extent of bioavailability.

혈장 중 시메티딘의 분석조건 설정 및 시메티딘 제제의 생물학적 동등성

김희규,이정민,윤미경,최성업,이상길,최영욱 중앙대학교 약학연구소 2002 약학 논총 Vol.16 No.-

Cimetidine is a histamine H_2-receptor antagonist, used for the treatment of endoscopically or radiographically conformed duodenal ulcer, pathologic GI hypersecretory condition, and active, benign, gastric ulcer. Simple method for determining of cimetidine in human plasma has been developed and validated. The procedure was linear in the range from 0.05 to 2 ug/mL for cimetidine. The intraday and interday validation for coefficient of variance (CV, %) and relative error (RE, %) were less than ±15%. Based on this analysis method, the bioequivalence of two cimetidine 400 mg tablet reference (Tagamet® 400mg) and test drug (AK-Cimetidine 400 mg) was evaluated according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty four healthy male volunteers, 66.79±7.98 kg in body weight and 23±2.73 in age, were divided into two groups and a randomized 2×2 cross-over study was employed. After one tablet containing 400 mg of cimetidine was orally administered, blood samples were taken at the predetermined time intervals and the concentrations of cimetidine in plasma were determined by protein precipitation method using HPLC with UV detector. Pharmacokinetic parameters such as AUC and Cmax were calculated and ANOVA was employed for the statistical analysis of parameters. The results were revealed that the differences in AUC and Cmax between two tablets were 1.3 % and 3.4 % respectively. The 90% confidence intervals for these parameters were also within ±20 % (e.g., log 0.9510∼log 1.0259 and log 0.9369∼log 1.1417 for AUC, Cmax, respectively). All of the above mentioned parameters met the criteria of KFDA guidelines for bioequivalence indicating that test drug tablet is bioequivalent to Tagamet® 400 mg tablet.