• Journal of Pharmaceutical Investigation
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• v.30 no.1
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• pp.33-37
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• 2000

One of the methods to increase the solubility of a drug is to use complexation with a cyclodextrin. Due to the hydrophobic nature of the interior cavity of the cyclodextrin, it has been known that undissociated lipophilic drugs can be included within the cyclodextrin by hydrophobic interaction. Recently, inclusion of hydrophilic or dissociated form of a drug has been investigated. In this study, the synergism of pH and complexation with $hydroxypropy-{\beta}-cyclodextrin\;(HP\;{\beta}\;CD)$ to increase the solubility of two oxicam derivatives was investigated. In addition, the effect of partition coefficient of dissociated and undissociated form of the drug on the extent of complexation with HP ${\beta}$ CD was studied. The solubility was measured by equilibrium solubility method. The solubility of tenoxicam and piroxicam increased exponentially with an increase in solution pH above the pKa of the drug in the presence and absence of HP ${\beta}$ CD. The solubility of the drugs increased linearly as a function of HP ${\beta}CD$ concentration at fixed pH. Although the stability constant of ionized species is less than that of the unionized species, the concentration of the ionized drug complex is greater than that of the unionized drug complex due to higher concentration of ionized species at pH 7.3.

• Journal of Pharmaceutical Investigation
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• v.28 no.4
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• pp.257-266
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• 1998

To improve the solubility and dissolution rate of acyclovir (ACV), which is low oral bioavailability due to its properties of slight solubility in water and incomplete gastrointestinal absorption, the solid inclusion complexes of ACV with ${\alpha}CD$, ${\beta}CD$, $DM{\beta}CD$ in molar ratio of 1:1 were prepared by the freeze-drying method. The inclusion complexes were investigated by solubility study, UV, IR and DSC. The dissolution rate of ACV was significantly increased by ACV-CDs inclusion complex formation in artificial intestinal fluid at pH 6.8. The enhanced dissolution rate of ACV could be due to an increase of solubility and the formation of an amorphous structures through inclusion complexation with CDs. Especially, $ACV-DM{\beta}CD$ inclusion complex enhanced the maximum plasma concentration levels and AUC following oral administration compared to those of ACV alone. The present results suggest that $ACV-DM{\beta}CD$ inclusion complex serves as a potential carrier for improving the solubility, the dissolution rate and the bioavailability of ACV.

• Journal of Pharmaceutical Investigation
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• v.22 no.2
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• pp.105-113
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• 1992

To improve the solubility and dissolution rate of trimethoprim (TMP), which is slightly soluble drug, its inclusion complexes were prepared and studied in this experiment. Inclusion complexes of TMP with ${\beta}-cyclodextrin$ and ${\beta}-cyclodextrin$ polymer (CDPS) were prepared according to Fenyvesi method. These were compared with TMP and its physical mixture with CDPS. Water, diluted hydrochloric acid and phosphate buffer solution were used as dissolution media. And accelerated stability test was studied at $50,\;70\;and \;80^{\circ}C$. It was found that solubility and dissolution rate of inclusion complexes were increased in water. Especially, the solubility and dissolution rate of TMP was found to be markedly increased by inclusion complexation with CDPS. In stability test, ${\beta}-cyclodextrin$ inclusion complexes were more or less stable than TMP alone. This tendency was not led in CDPS. Consequently, CDPS was useful in increasing dissolution rate and stability of TMP.

• Archives of Pharmacal Research
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• v.15 no.2
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• pp.176-183
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• 1992

The stabilizing effects of $\alpha$-$\beta$-$\gamma$- and dimethyl-$\beta$-cyclodextrins $(\alpha$-, $\beta$-, $\gamma$- and DM-$\beta-$-CyDs) on the degradation of hydrocortisone 17-butyrate (HC-17B) in aqueous solution was investigated. Hc-17B underwent a facile hydroxide ion-catalyzed rearrangement to the less active 21-butyrate ester by the apparent first-order kinetics, and maximum stability of HC-17B was obtained at around pH 4.0. The stability of HC-17B was increased by inclusion complexation with $\alpha$-, $\gamma$- and DM-$\beta$-CyD in the pH range of 2.0-8.0 examined, whereas $\beta$-CyD accelerated the degradation of HC-17B at the pH higher than 5.0. The effects of ionic strength, solvent, temperature and CyD concentration were also investigated. Stability constants and apparent degradation rate constants of HC-17B-$\gamma$-CyD and HC-17B-DM-$\beta$-CyD complexes were determined kinetically on the basis of 1:1 complexation. The results suggested that the inclusion complexation with $\gamma$-CyD or DM-$\beta$-CyD was most useful means to enhance the stability of the steroid.

• YAKHAK HOEJI
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• v.35 no.5
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• pp.372-378
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• 1991

To increase the stability and bioavailability of Omeprazole(OMP), which is used newly as a proton-pump inhibitor, inclusion complex of OMP with $\beta$-cyclodextrin($\beta$-CD) was prepared by coprecipitation method and its characteristics were ascertained by means of solubility test, DSC, IR, and the accelerated stability analysis. The type of OMP inclusion complex is classified as Bs-type on phase solubility diagram, and the stoichiometric ratio of OMP: $\beta$-CD complex is 1:2 and formation constant is 80.82/mole. The solubility of the complex could be increased remarkably by complexation compare with OMP. Degradation process of both OMP and OMP complex followed apparent first-order kinetics, of which degradation rate constants and activation energies are k$_{25}$=8.1$\times$10$^{-4}$/day, E$_{a}$=22 Kcal/mole (OMP), and k$_{25}$=4.65$\times$10$^{-6}$/day, E$_{a}$=35 Kcal/mole (complex), respectively. These results show the increase of the stability and solubility of OMP markedly, therefore it is believed that the improvement of stabilization for OMP by inclusion complexation might be practically available.

• Bulletin of the Korean Chemical Society
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• v.32 no.8
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• pp.2791-2794
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• 2011

• Bulletin of the Korean Chemical Society
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• v.13 no.5
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• pp.474-479
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• 1992

Molecular interaction between ${\alpha}$-cyclodextrin and aspirin was studied by UV, $^2H$-NMR and $^2H$-NMR spectroscopy analyses for solution complex and by FT-IR analyses for solid complex. The inclusion structure provides a basic understanding of the aspirin and ${\alpha}$-cyclodextrin interaction.

• Journal of Pharmaceutical Investigation
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• v.18 no.4
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• pp.181-186
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• 1988

Inclusion complex of sulfamethoxazole with ${\beta}-cyclodextrin$ was prepared by freeze-drying method in molar ratios of 1:1, 1:1.25, 1:1.5 and 1:1.75, and the complex formation was identified by ultraviolet and infrared spectroscopies, powder X-ray diffractometry and differential scanning calorimetry. Dissolution rate and solid state stability of the complex were investigated in comparison with those of sulfamethoxazole powder and the physical mixture of sulfamethoxazole with ${\beta}-cyclodextrin$. As a result, the dissolution rate and the stability of solid complexes in various relative humidity conditions increased more remarkably than those of sulfamethoxazole powder and physical mixture. But the difference according to molar ratio of the complex was not recognized.

• Bulletin of the Korean Chemical Society
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• v.27 no.9
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• pp.1397-1400
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• 2006

A detailed spectroscopic study ($^1H$ NMR, COSY, ROESY) of complexation of venlafaxine hydrochloride (VEN) with $\beta$-cyclodextrin ($\beta$--CD) was carried out in solution. The stoichiometry of the complex was determined to be 1 : 1 and penetration of aromatic ring into $\beta$-Cyclodextrin cavity was confirmed from primary rim side, with the help of ROESY spectral data. The structure of the venlafaxine hydrochloride-$\beta$-CD complex has been proposed. The association constant was determined to be 234 $M^{-1}$.

• Journal of the Korean Chemical Society
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• v.50 no.6
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• pp.515-517
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• 2006