• Journal of Pharmaceutical Investigation
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• 제34권4호
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• pp.269-274
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• 2004

To enhance the solubility and stability of lansoprazole (LAN), new proton pump inhibitor, we were prepared various molar ratio of inclusion complex with $2-hydroxypropyl-{\beta}-cyclodextrin$ (HPCD) and organic alkali agent, meglumine (MEG). Inclusion complex formation of LAN with HPCD was investigated by Differential Scanning Calorimetry and X-ray diffractometry. The aqueous solubilities of inclusion complexes, and the stabilities of 1:4 and 1:5 inclusion complexes in aqueous solutions containing different concentrations of MEG were examined. The stability of 1:5 LAN-HPCD inclusion complex containing MEG, which was equaled to amount of LAN, was performed in 0.9% NaCl and 5% dextrose solution. The formation of inclusion complex of LAN with HPCD was $A_L$ type and the molar ratio of complex was 1:1. The stability constant was $41.557\;M^{-1}$. As molar ratio of LAN to HPCD was increased, solubility of inclusion complex was increased. 1:5 LAN-HPCD inclusion complex was more stable than 1:4 LAN-HPCD inclusion complex. And as contained MEG amount in LAN solution was increased, stability of 1:4 and 1:5 LAN-HPCD inclusion complexes was improved. Also stability of 1:5 LAN-HPCD-MEG inclusion complex in 0.9% NaCl solution and 5% dextrose solution was similar to it in water at room temperature, but it was unstable at $40^{\circ}C$.

• Journal of Pharmaceutical Investigation
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• 제17권1호
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• pp.1-14
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• 1987

To increase the bioavailability of norfloxacin, inclusion complex of antimicrobial agent norfloxacin with ${\beta}-Cyclodextrin$ was prepared and studied by the solubility method, spectrophotometric methods(UV, IR, $^1H-NMR$), differential thermal analysis, powder X-ray diffractometry, the physical properties, the antimicrobial activity, DNA binding and in situ recirculation technique. The conclusions are summerized as following; 1) The inclusion complexation was identified by means of solubility, spectrophotometry(UV, IR, NMR), DTA and X-ray diffraction. 2) The molar ratio of $norfloxacin-{\beta}-cyclodextrin$ complex was 1 : 1. 3) The stability constant of $norfloxacin-{\beta}-cyclodextrin$ complex was $21.5\;M^{-1}$, and both true and apparent partition coefficients of the inclusion complex were larger than those of norfloxacin. 4) The time required to dissolve 60% $(T_{60}%)$ of the inclusion complex was 120 min. in distilled water and in the artificial intestinal juice, while norfloxacin did not reach to 60% dissolution within 120 min. 5) The antimicrobial activity of the inclusion complex against Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus aureus showed no significant difference compared to that of norfloxacin alone. 6) Studies on binding properties between the inclusion complex and norfloxacin alone to DNA according to equilibrium dialysis showed no significant differency. 7) In situ absorption rates (Ka) of inclusion complex and norfloxacin alone were 0.229 and $0.102hr^{-1}$, respectively.

• 한국식품과학회지
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• 제35권2호
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• pp.266-271
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• 2003

CD의 inclusion complex 형성능을 이용하여 대표적인 polyphenol계 천연 항산화 물질인 quercertin 및 catechin을 안정화시키는 분자 캡슐화 기술을 연구하였다. 먼저 ${\alpha}-,\;{\beta}-$, 그리고 ${\gamma}-CD$의 quercetin 및 catechin의 포접능을 비교하였다. Quercetin/catechin-CD inclusion complex 형성을 DSC thermogram을 이용하여 확인하였다. 또한 ${\beta}-CD$와의 포접에 따른 저용해성 quercetin과 catechin의 물에 대한 용해도의 변화를 관찰한 결과 inclusion complex 형성 시 용해도가 증가하는 것을 관찰할 수 있었다. Inclusion complex의 온도 및 pH에 대한 안정성을 검토한 결과 inclusion complex가 원래의 물질보다 높은 항산화능을 유지하였으며 특히 catechin의 안정성이 크게 향상되었다. Catechin-CD inclusion complex의 식품보존제로서의 적합성을 지방산인 linoleic acid를 시료로 검토하기 위하여 저장 중 과산화물가의 변화를 측정한 결과 포접된 catechin이 보다 높은 항산화능을 보였다. 이와 같은 용해도 및 항산화능의 증가로 볼 때 quercetin/catechin-CD inclusion complex는 신선식품의 보존제로 효과적으로 활용될 수 있는 것으로 판단된다.

• KSBB Journal
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• 제10권2호
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• pp.149-158
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• 1995

각종 CD와 여러 종류의 화합물, pH indicator, biostain, 아미노산, 천연배당체, 그리고 fatty acid 간의 inclusion complex 형성능을 비교하였다. Fatty acid가 각종 CD에 대한 포접형성능과 선택성 이 높아 CD 분리용 ligand로 적합함을 알았다. Fatty acid의 포접능과 선택성은 탄소쇄의 길이와 밀접한 상관관계를 나타내어 capric acid는 ${\alpha}$- CD와 palmitic acid는 ${\beta}$-CD와 높은 선택성을 보였다. Complex형성에 미치는 반융조건인 흔합 농도비, pH, ionic strength, 그리고 온도의 영향을 검토하였다. 적정 혼합 농도비는 CD가 50mM 그리고 lig and 인 fatty acid가 50mM 일 때 였으며 , 온도가 중 요한 형성조건으로 작용하였다. 포접되지 않은 CD 와 fatty acid가 포접 된 CD의 분자구조를 X-ray diffraction과 IR spectrum을 사용하여 비교 검토하였으며, DSC로 inclusion complex 형성반응의 en­t thalpy의 변화값(${\gamma}H$)을 측정하여 발열반응임을 확인하였다.

• Journal of Pharmaceutical Investigation
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• 제25권3호
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• pp.205-211
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• 1995

To increase the solubility of iodine and iodine releasing agents, which are used widely as a topical broad spectrum antiseptics and disinfectant sanitizers, its inclusion complexes were prepared and studied. Inclusion complexes of iodine with ${\beta}-cyclodextrin$ were prepared by coprecipitation method and complex formation was acertained by differential scanning calorimetry and microscopic observation. Iodine content of inclusion complex was determined by means of iodometry. Tablets containing inclusion complex were manufactured with sugar, citric acid, magnesium stearate, dextrose. Stability of inclusion complexes and tablets was evaluated by accelerated stability test, and comparing with PVP-iodine. During preparation, use of 50% ethanol solution is preferable to water as the medium because the former resulted in more stable complex for a month under accelerated storage conditions. Solubility of iodine in KI aqueous solution was 0.048 g/ml and lower than in 50% ethanol solution. Inclusion complex and its tablets were very stable at severe condition for one month, and comparable to PVP-iodine in the aspect of stability. Inclusion complex tabletswere not affected with citric acid, sugar, dextrose, and direct tableting method was recommendable because wet granulation using ethanol gave some release of included iodine during process.

• Journal of Pharmaceutical Investigation
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• 제15권1호
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• pp.15-21
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• 1985

The inclusion of ${\alpha}-cyclodextrin$ and ${\beta}-cyclodextrin$ with flurbiprofen in aqueous phase was investigated by UV absorption and circular dichroism spectroscopies. The inclusion complex in solid powder form were made by the freeze-drying and coprecipitation methods in molar ratio 1:1. The inclusion complex formation was confirmed by infrared absorption spectroscopy. The freeze-drying method was successful in obtaining the inclusion compounds compared with the coprecipitation method. The dissolution of solid flurbiprofen inclusion complex was examined in comparison with those of flurbiprofen alone. The inclusion complex obtained by freeze-drying method increased the dissolution rate.

• Journal of Pharmaceutical Investigation
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• 제25권4호
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• pp.283-289
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• 1995

The aim of this study is to increase the solubility and dissolution rate of clonixin by inclusion complex formation. Inclusion complexes of clonixin, a non-steroidal antiinflammatory drug, with ${\beta]-cyclodextrin$ were $2-hydrolrypropyl-{\beta]-cyclodextrin$ were prepared by freeze drying method. Inclusion complex formation of clonixin with cyclodextrins was determined by UV, IR and DSC. The apparent stability constants were calculated from the phase solubility diagrams. Dissolution rate and solubility of clonixin in water markedly increased by the complex formation.

• Archives of Pharmacal Research
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• 제18권1호
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• pp.22-26
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• 1995

The solubility and dissolution rate of naproxen (NPX) complexed with 2-hydroxypropyl-.betha.-cyc-lodextrin (2-HP.betha.CD) using coprecipitation, evaporation, freeze-drying and kneading method were investigated. Solubility of NPX linearly increased (correlation cefficient, 0.995) as $2-HP\betaCD$ concentraction increased, resutling in $A_l$ type phase solubility curve. Inclusion complexes prepared by four different methods were compared by different methods were compared by dfferential scanning calorimetry(DSC). The NPX showed sharp endothemic peak around $156^{\circ}C$ but inclusion complexes by evaporation, freeze-drying and kneading method showed very broad peak without distinct phase transtion temperature. In contrast, inclusion complex prepared by coprecipitation method resulted in detectable peak around $156^{\circ}C$ which is similar to NPX, suggesting incoplete formation of indusion co plex. Dissolution rate of inclusion complexes prepared by evaporation, frezz-drying and kneding except coprecipitation method was largely enhanced in the simultaed gastric and intestinal fluid when compared to NPX powder and commercial $NA-XEN^\registered$tablet. However, about 65% of NPX in gstric fluid. in case of inclusion complex prepared by coprecipitation method, formation of inclusion complex appeared to be incoplete, resulting in no marked enhancement of dissolution rate. From these findings, inclusion complexes of poorly water-soluble NPX with $2-HP\betaCD$ were useful to increase soubility and dissolution rate, resting in enhancement of bioavailability and minimization of gastrointestinal toxicity of drug upon oral administration of inclusion complex.

• Journal of Pharmaceutical Investigation
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• 제27권4호
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• pp.265-269
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• 1997

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.

• Bulletin of the Korean Chemical Society
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• 제13권2호
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• pp.179-183
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• 1992

A stable solid new inclusion complex with benzaldehyde and $permethyl-\beta-cyclodextrin$ was obtained by recrystallization method. The structure of the $benzaldehyde-permethyl-\beta-cyclodextrin$ inclusion complex in the solid and solution state have been studied by UV, IR, $^1H-NMR$, $^{13}C-NMR$ and FAB-mass spectroscopy.