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권호별목차 / 소장처보기

H : 소장처정보

T : 목차정보

藥劑學會誌 = Journal of Korean pharmaceutical sciences 10건

  1. [국내논문]   오메프라졸과 메글루민의 복합체 형성과 안정성  

    이계주 (충남대학교 약학대학 ) , 김성욱 (충남대학교 약학대학 ) , 도기찬 (충남대학교 약학대학 ) , 박종범 (충남대학교 약학대학 ) , 황성주 (충남대학교 약학대학)
    藥劑學會誌 = Journal of Korean pharmaceutical sciences v.27 no.4 ,pp. 253 - 263 , 1997 , 0259-2347 ,

    초록

    To investigate the interaction of omeprazole (OMP) and meglumine (MEG), a complex was prepared by freeze-drying method in ammoniacal aqueous medium at room temperature and subjected to IR, DSC, and 1H NMR analysis. In addition, the stability of the complex was tested by accelerated stability analysis, and the dissolution rate of both powder and enteric coated was determined pellet by paddle method. The results are as follows; i) IR, DSC, and $^{1}H$ NMR studies indicate the formation of inclusion complex between OMP and MEG probably by electrostatic forces as $[OMP]\;[MEGH]^+$ form in a stoichiometric ratio (1:1) of OMP : MEG. ii) The dissolution rate of enteric coated OMP-MEG complex pellet in simulated enteric fluid was 90.6% in 10 minutes, which may satisfy the requirement for the regulation of dissolution. iii) OMP-MEG complex were decomposed according to pseudo 1st order kinetics: while the decomposition of OMP showed a rate constant $(k_{25^{\circ}C})$ of $5.13{\times}10^{-4}{\cdot}\;day^{-1}$ , a half-life $(t_{1/2})$ of 1,350 days, a shelf-life $(T_{90%})$ 205 days and an activation energy of 23.53 kcal/mole. OMP-MEG complex inhibited a rate $(k_{25})$ of $2.92{\times}10^{-4}{\cdot}\;day^{-1}$ , a half-life $(t_{1/2})$ of 2,373 days, a shelf-life $(T_{90%})$ of 306 days and an activation energy of 20.18 kcal/mole. iv) OMP was stabilized markedly by the formation of OMP-MEG complex between OMP and MEG, and the humidity increased the stability of OMP-MEG complex by decreasing the decomposition rate $(k_{50^{\circ}C})$ from $1.27{\times}10^{-2}{\cdot}\;day^{-1}$ at 31% R.H. to $2.54{\times}10^{-2}{\cdot}\;day^{-1}$ at 90% R.H.

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  2. [국내논문]   무스콘의 ${\beta}$-시클로덱스트린 포접 복합체의 제조 및 평가  

    곽은선 (충남대학교 약학대학 ) , 조인숙 (충남대학교 약학대학 ) , 이계원 (충남대학교 약학대학 ) , 지웅길 (충남대학교 약학대학 ) , 박대규 (조선 무약)
    藥劑學會誌 = Journal of Korean pharmaceutical sciences v.27 no.4 ,pp. 265 - 269 , 1997 , 0259-2347 ,

    초록

    An inclusion complex of muscone with ${\beta}-cyclodextrin$ (CD), as a solid form of muscone, was prepared to increase the solubility of muscone. The molar ratio of muscone to ${\beta}-CD$ in complex was in the range of $1:1{\sim}1:5$ when prepared by freeze-drying method. The interaction of muscone with ${\beta}-CD$ in solid state was investigated by Infrared (IR) spectroscopy and differential scanning calorimetry (DSC). IR and DSC studies between $muscone-{\beta}-CD$ inclusion complex and physical mixture showed that $muscone-{\beta}-CD$ inclusion complex was prepared stably. From the amount of muscone incorporated in the inclusion complex, it was found that the molar ratio of muscone : ${\beta}-CD$ was 1:1. Relative spatial position of muscone and ${\beta}-CD$ was observed by Hyperchem molecular modelling program.

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  3. [국내논문]   $OMP-{\beta}-CD$ 포접화합물의 물리화학적 성질, 안정성 및 피부 투과 실험  

    이상영 (충남대학교 약학대학 ) , 이계원 (충남대학교 약학대학 ) , 최현순 (충남대학교 약학대학 ) , 지웅길 (충남대학교 약학대학)
    藥劑學會誌 = Journal of Korean pharmaceutical sciences v.27 no.4 ,pp. 271 - 277 , 1997 , 0259-2347 ,

    초록

    Because omeprazole(OMP) is very unstable in aqueous condition, $OMP-{\beta}-CD$ , the inclusion complex of OMP and ${\beta}-cyclodextrin({\beta}-CD)$ was made and physicochemical properties of it were compared with those of OMP. Skin permeability of OMP and $OMP-{\beta}-CD$ in propylene glycol vehicle and the reciprocal action of ${\beta}-CD$ with various enhancers were examined through hairless mouse. Adhesive patches were prepared with polyisobutylene and the skin permeability and stability of OMP were investigated. The inclusion complex showed higher solubility and lower partition coefficient than OMP itself. DMSO, 1-methyl 2-pyrrolidone and sodium cholate had an enhancing effect. However ethanol and polysorbate 80 hardly showed the enhancing effect of OMP. When sodium lauryl sulfate and sodium cholate as enhancer were added in patch, the former case showed higher permeability of OMP.

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  4. [국내논문]   이부프로펜의 가용화  

    이장원 (성균관대학교 약학대학 ) , 박은석 (성균관대학교 약학대학 ) , 지상철 (성균관대학교 약학대학)
    藥劑學會誌 = Journal of Korean pharmaceutical sciences v.27 no.4 ,pp. 279 - 286 , 1997 , 0259-2347 ,

    초록

    In order to formulate 2% ibuprofen solution, the effects of various solublizing agents, such as cosolvents (propylene glycol, polyethylene glycol, glycerin), a complexing agent $(CELDEX{\circledR}\;CH20)$ , surfactants $(Poloxamers\;and\;Cremophor{\circledR}\;RH40)$ on the solubility of ibuprofen in aqueous solution were evaluated. Among them, Poloxamer 407 and $Cremophor{\circledR}$ RH40 showed the excellent capacity on the solubilization of ibuprofen. After 2% ibuprofen solution of choice were administered orally to rats, in reference to a 2% ibuprofen syrup in the market, the pharmacokinetic parameters were determined. The absorption rate of ibuprofen from the solution was higher than that from the suspension.

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  5. [국내논문]   O/W 유제의 물리적 안정성에 대한 PVP의 영향  

    오인준 (전남대학교 약학대학.약품개발연구소 ) , 이미영 (전남대학교 약학대학.약품개발연구소 ) , 이정민 (영진약품공업(주) 중앙연구소 ) , 이용복 (전남대학교 약학대학.약품개발연구소 ) , 신상철 (전남대학교 약학대학.약품개발연구소 ) , 최보길 (전남대학교 약학대학.약품개발연구소 ) , 김종국 (서울대학교 약학대학)
    藥劑學會誌 = Journal of Korean pharmaceutical sciences v.27 no.4 ,pp. 287 - 293 , 1997 , 0259-2347 ,

    초록

    To make a stable o/w emulsion, the effects of egg lecithin as an emulsifier and polyvinylpyrrolidone (PVP) as an auxiliary emulsifier on the physical stability of emulsion were investigated. The oil-in-water emulsion system was manufactured by microfluidizer and evaluated the physical stability. Average particle size and size distribution of emulsion was measured by dynamic light scattering analyzer and interfacial tension was measured. From the interfacial tension tested, critical micelle concentration of the egg lecithin was 0.1 %w/v and optimal concentration for the preparation of emulsion was 1.0 %w/v. The mean particle size was about $0.2\;{\mu}m$ which was suitable for injections. The short-term accelerated stability studies were conducted by centrifugation, freeze-thaw method and shaking of the emulsion samples. The addition of PVP was caused the reduction in the particle size and improved the physical stability of emulsion. These results suggested that a mixed interfacial film comprising the egg lecithin and PVP was formed at the o/w interface and it was effective in preventing phase separation under thermic or mechanical stress. We used antineoplaston A10 (A10) as a model drug which is peptide and amino acid derivative having a action to the living organism against the development of neoplastic growth by a nonimmunological progress. It has a poor solubility in water and there may be a difficulty in formulation of A10. Emulsion formulation study about A10 was performed. Solubility of A10 in emulsion was about five times as high as that in water. From the results of solubility and partition coefficient, almost A10 molecules in o/w emulsion exist in the interface between oil and water.

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  6. [국내논문]   흰쥐에 경구 투여시 히드록시프로필-베타-시클로덱스트린과 니트렌디핀 고체분산에 의한 생체이용률 증가  

    용철순 (영남대학교 약학대학)
    藥劑學會誌 = Journal of Korean pharmaceutical sciences v.27 no.4 ,pp. 295 - 301 , 1997 , 0259-2347 ,

    초록

    Nitrendipine, a slightly soluble calcium channel blocking agent forms a solid dispersion system with $hydroxypropyl-{\beta}-cyclodextrin$ , which exhibits better dissolution characteristics than the uncomplexed drug. The dissolution rate of nitrendipine was markedly increased in solid dispersion system in pharmacopeial disintegration media at pH 1.2 and pH 6.8. Four different dosage forms of nitrendipine were administered to rats: (a) nitrendipine in the solution of PEG 400; (b) nitrendipine solid dispersion system with $hydroxypropyl-{\beta}-cyclodextrin$ in a molar ratio of 1:2 by solvent evaporation method and administered in capsule form; (c) physical mixture of nitrendipine with $hydroxypropyl-{\beta}-cyclodextrin$ in a molar ratio of 1:2 and administered in capsule form; (d) nitrendipine alone administered in capsule form. Relative bioavailability after the oral administration of various dosage forms to rats with a dose of 10 mg/kg equivalent to nitrendipine was compared with that of nitrendipine in the solution of PEG 400. The AUC of solid dispersion was significantly bigger than that of nitrendipine powder. $T_{max}$ of solid dispersion was significantly shorter and $C_{max}$ was higher than that of nitrendipine powder. These results indicate that the bioavailability of nitrendipine could be improved markedly by inclusion complexation. An interesting correlation also appears to exist between the in vitro dissolution data and the area under the plasma concentration-time curves.

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  7. [국내논문]   프로리포솜을 이용한 클렌부테롤의 경피흡수 제제화  

    이영주 (서울대학교 약학대학 ) , 정석재 (서울대학교 약학대학 ) , 이민화 (서울대학교 약학대학 ) , 심창구 (서울대학교 약학대학)
    藥劑學會誌 = Journal of Korean pharmaceutical sciences v.27 no.4 ,pp. 303 - 311 , 1997 , 0259-2347 ,

    초록

    Proliposomal patch of clenbuterol, ${\beta}_2-agonist$ bronchodilator, was prepared and its feasibility as a novel transdermal drug delivery system was examined. Proliposomal granules containing clenbuterol was prepared by a standard method using sorbitol and lecithin with (Rx 2) or without cholesterol (Rx 1). The porous structure of sorbitol in the proliposomes was maintained allowing tree flowability of the granules. Following contact with water, the granules were converted probably to liposomes almost completely within several minutes. It indicates that proliposomes may be hydrated, when they are applied on the skin under occlusive condition in vivo, by the sweat to form liposomes. Clenbuterol release from Rx 1 and Rx 2 proliposomes to pH 7.4 isotonic phospate buffer (PBS) across cellulose membrane (mol. wt. cut-off of 12000-14000) was retarded significantly compared with that from the mixture of clenbuterol powder and blank proliposomes. Interestingly, proliposomes prepared with lecithin and cholesterol (i.e., Rx 2 proliposomes) showed much more retarded release of clenbuterol than proliposomes prepared only with lecithin (i.e.. Rx 1 proliposomes), indicating that clenbuterol release from proliposomes can be controlled by the addition of cholesterol to the proliposomes. Proliposomal patches were prepared using PVC film as an occlusive backing sheet, two sides adhesive tape (urethane, 1.45 mm thickness) as a reservoir for proliposome granules and Millipore MF-membrane (0.45 mm pore size) as a drug release-controlling membrane. Rx 1 or Rx 2 proliposomes containing 4.6 mg of clenbuterol were loaded into the reservoir of the patch. Clenbuterol release from the patches to pH 7.4 PBS was determined using USP paddle (50 rpm)-over-disc release method. Clenbuterol release from the proliposomal patches was much more retarded even than from a matrix type clenbuterol patch (Boehringer Ingelheim ltd). Being consistent with clenbuterol release from the proliposomal granules, the release from the patches was highly dependent on the presence of cholesterol in the proliposomes : Patches containing Rx 2 proliposomes showed several fold slower drug release than patches containing Rx 1 proliposomes. When the patch containing Rx 1 proliposomes was applied on to the back of a hair-removed rat, clenbuterol concentration in the rat blood was maintained during 6-72 hrs. Transdermal absorption of clenbuterol from the patch was accelerated when the patch was prehydrated with 50 ml of pH 7.4 PBS before topical application. Above results indicate that sustained transdermal delivery of clenbuterol is feasible using proliposomal patches if the cholesterol content and pore size of the release rate-controlling membrane of patches, for example, are appropriately controlled.

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  8. [국내논문]   파모티딘-양이온 교환수지 복합체의 약물방출 특성 및 흰쥐에서의 체내동태  

    신동선 (중앙대학교 약학대학 ) , 송우헌 (중앙대학교 약학대학 ) , 최영욱 (중앙대학교 약학대학)
    藥劑學會誌 = Journal of Korean pharmaceutical sciences v.27 no.4 ,pp. 313 - 321 , 1997 , 0259-2347 ,

    초록

    Ion exchange resin complexes of famotidine have been prepared by the reaction of famotidine solution with activated ion exchange resins. Complex formation efficiency between famotidine and ion exchange resin was about $80{\sim}90%$ in average, calculated by HPLC determination. Drug release characteristics from the resin complexes were evaluated by the modified percolation method. Famotidine release was dependent on the type of ion exchange resins. In the case of weakly acidic resin complexes, the cumulative released amount of famotidine was more than 90% for 1hr in pH 1.2 buffer solution. However, in the case of strongly acidic resin complexes, it was less than 5% for 3hr in the same medium. Strongly acidic resins revealed some advantages over weakly, acidic resins for overcoming instability of famotidine in gastric juice. In addition, strongly acidic resin complexes showed controlled release of famotidine in pH 6.8 buffer solution, showing the result of about 60 to 70% of drug release for 5hr. After oral administrations of famotidine-resin complexes to rats as dose of 40 mg equivalent/kg, the pharmacokinetic parameters of famotidine were obtained by model independent analysis and compared with those of famotidine solution or suspension. $C_{max}$ of famotidine-resin complex was lower than that of famotidine solution or suspension. MRT, MAT, and MDT of the complexes were greater than those of famotidine solution or suspension. From these results, it was expected that famotidine was released slowly from the complexes and absorbed continuously into systemic circulation. It was recognized that drug release from the complexes was the rate-limiting step in drug absorption, since there were close correlations between in vitro drug release and in vivo pharmacokinetic parameters.

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  9. [국내논문]   이프리플라본 서방정 제조 및 약동학적 평가  

    박경호 (서울대학교병원 약제부)
    藥劑學會誌 = Journal of Korean pharmaceutical sciences v.27 no.4 ,pp. 323 - 329 , 1997 , 0259-2347 ,

    초록

    Ipriflavone is non-hormonal antiosteoporotic drug which inhibits bone resorption by reducing recruitment and/or differentiation of osteoclasts, and stimulates proliferation and differentiation of osteoblast, and also enhances calcitonin secretion in the presence of estrogen. Although some kinds of immediately-released preparation of ipriflavone are available in commercial market, in present study, we tried to formulate sustained-release tablet using coating method with hydrophobic and hydrophilic coating materials. In vitro dissolution test was applied to evaluate sustained-release patterns of several test preparations (Test tablet A, B and C) designed using different preparation method or different compositions. From the results of dissolution test, test tablet A which showed suitable dissolution profile was selected as the candidate of new product. Pharmacokinetic evaluation of test drug, ipriflavone sustained-release tablets, was conducted in 6 beagle dogs weighing $11.5{\pm}0.5\;Kg$ compared with $Theobon^{\circledR}$ tablet, immediately-released tablet (Kukjae Pharm. Co.) as reference drug. Two products were randomly administered to 6 beagle dogs, and after 1 week, cross-over study was conducted. From the present study, AUC and $T_{max}$ of test product were significantly different from those of reference product (p $(AUC\;:\;3646.28{\pm}472.56\;vs\;3646.28{\pm}472.56\;ng{\cdot}hr/ml,\;T_{max}\;:\;4.33{\pm}1.03\;vs\;1.42{\pm}0.38\;hr)$ . But $C_{max}$ was not significantly different between two products (p>0.05) $(\;512.52{\pm}48.18\;vs\;443.97{\pm}140.53\;ng/ml)$ . From the results of pharmacokinetic evaluations, it was noted that absorption amount of test product was increased, but absorption rate was delayed and $C_{max}$ of two products were not changed. And it was concluded that redesign of the sustained-release preparation which has a lower content of iprifavone rather than test tablet A must be considered.

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  10. [국내논문]   건강한 성인 지원자를 대상으로 한 필로칼핀 저작정의 타액분비 유도 및 타액중 용출패턴 평가  

    박경호 (서울대학교병원 약제부)
    藥劑學會誌 = Journal of Korean pharmaceutical sciences v.27 no.4 ,pp. 331 - 335 , 1997 , 0259-2347 ,

    초록

    Xerostomia is caused by organic or functional changes affecting the salivary system at different levels. Patients suffering from xerostomia may also complain of an oral burning sensation, ulceration or soreness, difficulty in swallowing, and poor denture retention. And pilocarpine is administered orally to induce salivary secretion. In Seoul National University Hospital(SNUH) pharmacy, the pilocarpine chewing tablets are prepared and supplied to patients of xerostomia in request of the dental hospital in SNUH. And we tested the salivary flow induction and the dissolution patterns of these products in saliva by a double-blind, sequential cross-over trials to eight healthy human volunteers with placebo. The pilocarpine chewing tablet contained 5 mg of pilocarpine, and placebo consisted of same materials as test drug, but didn't contain pilocarpine. In vivo experiment, all subjects were instructed to chew as 60-80 times/min. Mixed saliva was collected in the ranges of intervals such as 0-2, 2-5, 5-10, 10-15, 15-20, 20-30, 30-45 and 45-60 min after pilocarpine chewing tablet or placebo administration. Saliva volume was measured in each collecting time interval, and saliva pilocarpine concentrations were determined by reversed phase HPLC. The 82.5 percent $(4.13{\pm}0.69\;mg)$ of pilocarpine was extracted from chewing tablets during mastication of 60-80 times per minute for 60 minutes. Among these dissolved amounts, 90 percent was extracted within 20 minutes. The salivary flow rates were more increased in a group who administered pilocarpine chewing tablet at the interval of 5-10, 10-15, 20-30 and 45-60 min rather than a placebo-group, but only extracted amount of pilocarpine at 45-60 min interval is significanly different between two groups (p $46.36{\pm}9.72\;ml\;and\;39.09{\pm}7.81\;ml$ , respectively, and were not significantly different between two groups.

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