• Journal of Pharmaceutical Investigation
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• v.26 no.2
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• pp.71-82
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• 1996

This study has been undertaken to evaluate hydrophobic cyclodextrin(CD) derivatives as a sustained release carrier of azidothymidine(AZT), AZT, which has potent activity against AIDS and AIDS-related complex as thymidine analogue, has been reported that it has significant toxicity and short half life. Therefore, it is necessary to design sustained release oral dosage form to avoid undesirable side effects attributable to an excessive plasma concentration and to reduce the frequency of administration of AZT. Inclusion complexes of AZT with $acetyl-{\beta}-cyclodextrin\;(AC{\beta}CD)$ and $triacetyl-{\beta}-cyclodextrin(TA{\beta}CD)$ were prepared by solvent evaporation method. Interactions of AZT with CD were investigated by Differential Scanning Calorimetry(DSC) and Infrared Spectrophotometry(IR). The decreasing order of water solubilities of AZT and AZT-CD inclusion complexes were as follows; $AZT\;(27.873{\pm}0.015,mg/ml)\;>\;AZT-AC{\beta}CD\;(3.377{\pm}0.003)\;>\;AZT-TA{\beta}CD\;(2.528{\pm}0.001)$. Partition coefficients of $AZT-AC{\beta}CD\;and;\AZT-TA{\beta}CD$ inclusion complexes were increased by 1.27-fold, 1.54-fold in pH 1.2 and 1.32-fold, 1.47-fold in pH 6.8 in comparison with that of AZT. The mean dissolution time (MDT, min) which represents the rapidity of dissolution rate of AZT, $AZT-AC{\beta}CD,\;AZT-TA{\beta}CD$ were 5.12, 14.02 and 19.38 min in pH 1.2 and 2.52, 15.19 and 18.19 min in pH 6.8. AZT was very rapidly and completely dissolved in pH 1.2 and pH 6.8 within 5 minutes. But AZT-CD inclusion complexes showed the sustained release pattern in comparison with AZT alone. The simultaneous in situ nasal and jejunal recirculation study to compare the intrinsic absorptivity and the property of absorption sites revealed that the absorption of $AZT-TA{\beta}CD\;(N:35.35{\pm}1.08%,\;J:27.47{\pm}1.18%)$ was more than that of $AZT\;(N:16.89{\pm}2.25%,\;J:15.86{\pm}2.33%)$. The above results suggest that $TA{\beta}CD$ which is a hydrophobic cyclodextrin may serve as sustained release carrier with absorption enhancing effect.

• Journal of Pharmaceutical Investigation
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• v.24 no.2
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• pp.95-104
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• 1994

Inclusion complexes of ketoconazole(KT) with ${\alpha}^_$, ${\beta}^_$cyclodextrin(CD) and $dimethy1-{\beta}-cyclodextrin$ (CD) and $dimethy1-{\beta}-cyclodextrin(DM{\beta}CD)$ as nasal absorption enhancer were prepared in 1: 2 molar ratios by freeze-drying and solvent evaporation methods. In order to compare with the intrinsic absorptivity of KT in the jejunum(J) and the nasal cavity(N), the in situ simultaneous perfusion method was employed. The in situ recirculation study revealed that KT-CD inclusion complexes with the greater stability constant and the faster dissolution rate proportionally increased the absorption of KT in the J and N of rats. The rank order of apparent KT permeability$(P_{app}\;:\;cm/sec\;{\time}\;1O^{-5}{\pm}S.E.)$, corrected by surface area of absorption, was $5.10{\pm}0.3(N,\; KT-DM{\beta}CD)$ )> $4.13{\pm}0.4(N,\;KT-{\beta}-CD)$ )> $3.52{\pm}0.2(N,\;KT-{\alpha}-CD)$ )> $2.76{\pm}0.3(J,\; KT-DM{\beta}CD)$ )> $2.61{\pm}0.5(J,\;KT-{\beta}-CD)$ )> $2.42{\pm}0.4(J,\;KT-{\alpha}-CD)$ at pH 4.0. The in crease in permeability of $KT-DM{\beta}CD$ inclusion complex was 2.6 folds in the J and 4.5 folds in the N when the perfusing solution was changed from the buffer(pH 4.0) to saline. The absorption rate of $KT-DM{\beta}CD$ inclusion complex after nasal administration was more rapid than those of ketoconazole alone and $KT-DM{\beta}CD$ inclusion complex after oral administration to rats. In comparision with an oral administration of ketoconazole suspension in corn oil, the relative bioavailability was calculated 137.3% for the oral and 195.0% for nasal $KT-DM{\beta}CD$ inclusion complex in rats. The present results suggest that $KT-DM{\beta}CD$ inclusion complex may serve as a potential nasal absorption enhancer for the nasal delivery of ketoconazole.

• KSBB Journal
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• v.21 no.2
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• pp.151-156
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• 2006

Vitamin-C is one of the typical bioactive substances widely used in the cosmetic and pharmaceutical applications. It is well known that the bioavailability of vitamin-C decreases with time because it is spontaneously oxidized in the presence of oxygen. In this study, vitamin-C inclusion complexes were prepared by formulating vitamin-C with 2-hydroxypropyl-${\beta}$-cyclodextrin (HP-${\beta}$-CD) to protect vitamin-C from being oxidized. Vitamin-C inclusion complexes were prepared by a solvent evaporation method using a rotary evaporator and various solvents of different dielectric constant such as ethanol, methanol and distilled deionized water to investigate the effect of solvent polarity on the stability of vitamin-C. To estimate the stability of inclusion complexes, samples were stored in a 50 mM phosphate buffer solution of pH 7.0 for 24 hours at $25{\pm}0.1^{\circ}C$ and the degradation rate of vitamin-C was calculated using a high performance liquid chromatography. The stability of vitamin-C was observed to improve with the increase of solvent polarity.

• Journal of Photoscience
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• v.3 no.3
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• pp.153-158
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• 1996

The effects of $\alpha$- and $\beta$-cyclodextrins (CD) on the twisted intramolecular charge transfer (TICT) behavior of p-N,N'-dimethylaminobenzoic acid (DMABA) in buffered aqueous solution have been investigated by examining formation and decay behaviors of the TICT-typical dual fluorescence. The ratio of the TICT emission to the normal emission (I$_a$/I$_b$) increases linearly $\alpha$-CD concentration increases, while in the presence of $\beta$-CD it shows nonlinear dependences on the CD concentration. The analysis of the CD-dependent changes of the I$_a$/I$_b$ and absorption spectra demonstrates formation of 1:1 inclusion complexes between DMABA and CDs. The decay time of the normal emission (ca. 700 ps) is little affected by the formation of $\alpha$-CD inclusion complex, whereas it increases upto ca. 1.6 ns upon formation of $\beta$-CD inclusion complex. The TICT emission for the $\beta$-CD inclusion complex exhibits two decay components while it shows a single component for the $\alpha$-CD inclusion complex, indicating formation of one or two types of inclusion complex in the presence of $\alpha$-CD or $\beta$-CD, respectively. These results are attributed to the CD cavity size dependence on patterns of complexation between CDs and DMABA. The CD size dependences of the TICT fluorescence properties with the orientation of the guest molecule demonstrate that the specific hydrogen bonding between the carboxylic acid group and water plays an important role in the excited-state TICT.

• Proceedings of the PSK Conference
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• 2001.04a
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• pp.220.2-220.2
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• 2001

• Archives of Pharmacal Research
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• v.27 no.12
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• pp.1290-1294
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• 2004

The ${\beta}$-blockers possess at least one chiral center and the S(-)-enantiomer shows higher affinity for binding to the ${\beta}$-adrenergic receptors than antipode. The stability constants of acebutolol, celiprolol, propranolol and terbutaline in the inclusion complexes with single-isomer heptakis (2,3-dimethyl-6-sulfato)- ${\beta}$-cyclodextrin (HDMS-${\beta}$-CD) were determined by capillary electrophoresis. The approximation and linear double reciprocal methods were adapted with comparable results. Among the ${\beta}$-blockers studied, propranolol had the lowest stability constant but the highest enantioselectivity, indicating that the magnitudes of the stability constants carried little information about enantioseparation. The magnitudes of enantioselectivities between the enantiomer pair were in the order of propranolol > celiprolol > terbutaline > acebutolol.

• Polymer(Korea)
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• v.38 no.3
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• pp.338-350
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• 2014

Cellulose acetate (CA) fiber mats containing inclusion complexes of asiaticoside (AC) in 2-hydroxypropyl-${\beta}$-cyclodextrin ($HP{\beta}CD$) for potential usage as wound dressings were developed. The AC/$HP{\beta}CD$ complex-loaded CA fibers at various $HP{\beta}CD$ to AC molar ratios of 0.5, 1, and 2 were prepared in 90:10 v/v mixture of 80% (v/v) acetic acid and N,N-dimethylacetamide (DMAc) via electrospinning. The maximum released amounts of AC depended on the $HP{\beta}CD$ content and were much greater than those released from the AC-loaded CA fiber mat. In the in vitro study, indirect cytotoxic evaluation with human dermal fibroblasts (HDFa) showed that these materials released no substances in the levels that were harmful to the cells and the cells appeared to attach and proliferate well on these substrates. However, only the CA fiber mats containing AC/$HP{\beta}CD$ complexes at the $HP{\beta}CD$ to AC molar ratio of 0.5 was effective in upregulating the production of collagen of the cultured cells.

• KSBB Journal
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• v.17 no.1
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• pp.54-58
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• 2002

Curdlan gel containing various hydrophobic materials was prepared. The homogenized suspension of curdlan and hydrophobic materials was healed at $100^{\circ}C$. The curdlan gel can contain hydrophobic material up to 27%(v/v). When gel was compressed, only water in the gel was removed. When immersed in water, the dried gel absorbed water and became the original wet gel. The syneresis of gel decreased with the concentration of hydrophobic material added. DHA content of dried gel was about 90%. $\beta$-cyclodextrin inclusion complexes containing DHA were prepared with addition of water and ethanol. X-ray diffractograms of complexes showed a specific peak at 7-$8^{\circ}C$ and FT-IR spectrum of complex showed a specific C=O peak at $1745\textrm{cm}^{-1}$. Inclusion complex containing DHA was microcapsulated with curdlan and pullulan.

• Journal of Pharmaceutical Investigation
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• v.26 no.1
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• pp.1-11
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• 1996

Biphenyldimethyldicarboxylate (PMC), which has been used to treat hepatitis, is insoluble in water, therefore it has low bioavailability after oral administration. For the purpose of increasing the dissolution rate of PMC, the physical mixtures and inclusion complexes of PMC and $dimethyl-{\beta}-cyclodextrin\;(DM\;{\beta}CD)\;or\;hydroxypropyl-{\beta}-cyclodextrin\;(HP{\beta}CD)$ in molar ratio of 1 : 1 and 1 : 2 were prepared by solvent evaporation method. Mixed micelles of PMC were prepared by reacting PMC with bile salts [sodium cholate(NaC), sodium glycocholate (NaGC)] and oleic acid (OA) or palmitoylcarnitine chloride(PCC). Chloroform/water partition coefficient (PC) of PMC was 36.14 in artificial gastric juice (AGJ) and 33.47 in artificial intestinal juice (AIJ), respectively, on the other hand octanol/water PC was 63.36. PMC formulation was prepared by reacting PMC with PEG400-glycerin system(95 : 5, 90 : 10, respectively) and PEG400-PEG4000-glycerin system (70 : 25 : 5, 65 : 25 : 10, respectively). Dissolution test was performed in AGJ and AIJ by paddle method at $37{\pm}0.5^{\circ}C$. The dissolution rates of PMC tablets on the market were 5.74% and 8.26% at AGJ and AIJ, respectively and marketed PMC capsules were 22.14% and 28.64% at AGJ and AIJ, respectively. The dissolution rates of inclusion complexes of PMC with $DM{\beta}CD$ and $HP{\beta}CD$ in a molar ratio of 1 : 1 were more fast than those of corresponding physical mixtures. The decreasing order of dissolution rates was as follows; PMC-PEG400-PEG4000-glycerin formulation > PMC-PEG400-glycerin formulation > mixed micelles > CD inclusion complexes. The dissolution rates of PMC-PEG400-glycerin and PMC-PEG400-PEG4000-glycerin formulation were most fast and the percentage of dissolution was almost 100% within 20 minutes. And their dissolution rates after 120 minutes were markedly increased as compared with capsules on the market (4.0-fold and 3.2-fold in PMC-PEG400-glycerin formulation at AGJ and AIJ, respectively, and 4.8-fold and 3.7-fold in PMC-PEG400-PEG4000-glycerin formulation at AGJ and AIJ, respectively).

• KSBB Journal
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• v.27 no.2
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• pp.109-113
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• 2012

This research was to examine the effects of various cyclodextrins on the solubility and stability of prodigiosin in seawater. Among them, ${\beta}$-cyclodextrin was found to have the best efficiency and formation of the inclusion complex was saturated when prodigiosin and ${\beta}$-cyclodextrin were mixed in a ratio of 1:8 and shaken at $25^{\circ}C$ and pH 8.0 for 6 h. The maximum algicidal activity against Chattonella antiqua using the inclusion complex stored at $4^{\circ}C$ for 5 weeks of culture was obtained, $52.28{\pm}3.41%$, which was about 5.0 fold higher than that of control. Our results suggest that inclusion complexes of prodigiosin and ${\beta}$-cyclodextrin could serve as effective algicidal agents.