• Korea-Australia Rheology Journal
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• 제12권2호
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• pp.93-100
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• 2000

The interactions between methylated $\beta$-cyclodextrin (CD) and hydrophobically modified alkali-soluble associative polymers (HASE) were examined by a rheological technique. The effect of "capping" of hydrophobes by methylated $\beta$-cyclodextrin on the viscosity and modulus was evaluated. Model HASE polymers with $C_1$to $C_{20}$ alkyl hydrophobic groups ethoxylated with~10 moles of ethylene-oxide (EO 10) and at concentrations up to 3 wt% were examined. With the addition of methylated $\beta$-CD, the steady shear viscosity profiles shift from a Newtonian profile to one that display a shear-thinning characteristic. Significant "capping" of the hydrophobes occurs for HASE polymers with $C_{l2}$, $C_{16}$ and $C_{20}$ hydrophobes as reflected by the large reduction in the viscosity. However, the steady shear viscosity remains constant when the concentration of $\beta$-CD exceeds 1 wt%, suggesting that $\beta$-CD is not able to fully encapsulate the hydrophobes of the HASE polymer. The temperature variation plots indicate that the activation energy of the HASE-EO10-$C_{20}$ system and $\beta$-CD is dependent on the magnitude of the applied shear stress. These results further reinforce the hypothesis that $\beta$-CD is not able to completely remove all the hydrophobic associations.phobic associations.

• 약학회지
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• 제31권1호
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• pp.42-44
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• 1987

Ziperol, anti-tussive, is considerably bitter. Therefore, it is necessary to mitigate the bitterness in ziperol syrup for children. In this experiment, it was attempted to mitigate the bitterness of zipeprol by means of polymers such as $\beta$-cyclodextrin, arabic gum, HPMC(hydroxypropyl methylcellulose), PEG 2000(polyethyleneglycol 2000), PVP(polyvinylpyrrolidone). Caffeine was used as the reference standard of bitterness. In the result of this experiment, $\beta$-cyclodextrin, would mitigate the bitterness of zipeprol more largely than any other polymers. Arabic gum was the second choice which would mitigate the bitterness of zipeprol.

• 분석과학
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• 제17권1호
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• pp.16-22
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• 2004

Inclusion complexes of the p-nitrophenol with ${\beta}$-cyclodextrin (CD), sulfated ${\beta}$-CD, and ${\beta}$-CD polymer cross-linked with epichlorohydrine (EP) were prepared and characterized by Raman spectroscopy. The intensity of vibration peaks of the C-O and C-N at 1284 and $856cm^{-1}$ of the p-nitrophenol in the presence of EP-linked CD polymer was remarkably increased, respectively. The vibration modes at 1284 and $856cm^{-1}$ are assigned to the out-of phase C-C-O stretching mode and the C-N stretching mode, respectively. The vibration peaks at 1284 and $856cm^{-1}$ increased with increasing the content of EP-linked CD polymers, while decreased with increasing the p-nitrophenol content. Furthermore, the vibration mode of the $NO_2$ symmetric stretch at $1344cm^{-1}$ enhanced with increasing the content of p-nitrophenol.

• 한국식품과학회지
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• 제29권2호
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• pp.302-308
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• 1997

Epichlorohydrin을 이용하여 ${\beta}-CD$ 중합체를 제조한 후 차단분자량 10,000인 막(YM 10)을 이용하여 수용성 ${\beta}-CD$ 중합체와 불용성 ${\beta}-CD$ 중합체를 분리하였다. 최적분리 조건은 막횡단압력 51.7 kPa, 운용온도 $35^{\circ}C$, 용적농축비 10이었으며, 이때의 flux는 $0.025\;mL/cm^{2}/min$ 이었다. 겔 투과 크로마토그래피 결과 수용성 중합체의 중합도는 $2{\sim}8$, 불용성 중합체는 10 이상으로 나타났으며, 이들 ${\beta}-CD$ 중합체의 소수성 물질들과의 포접 형성능을 비교하였다. 색소물질인 4-dimethylaminoazobenzene과 methyl red를 이용하여 ${\beta}-CD$와 ${\beta}-CD$ 중합체와의 포접 능력을 측정하였다. 포접 복합체 형성 여부를 간접적으로 알 수 있는 분광학적 변화를 측정한 결과 두 색소물질 흡광도의 강도가 증가하였으며 최대 흡광도 위치가 변하였다. 감귤류의 주된 flavonoid이며 쓴맛물질인 naringin은 물에 대한 용해도가 낮으나 ${\beta}-CD$ 중합체과 포접복합체를 형성함으로써 수용성이 증가하였다. ${\beta}-CD$ 단위체보다는 ${\beta}-CD$ 중합체의 포접능력이 훨씬 강하였으며, 중합도별 포접능력에 있어 불용성 ${\beta}-CD$ 중합체와 수용성 ${\beta}-CD$ 중합체간에 큰 차이는 나타나지 않았다. ${\beta}-CD$ 단위체는 용해도가 극히 낮아 쓴맛 물질 제거 이용에 있어 제한이 있는 반면, 수용성 ${\beta}-CD$ 중합체는 용해도가 높아 감귤류 등으로부터 쓴맛 성분을 감소시키는 공정에의 이용 가능성이 높은 것으로 나타났다.

• Journal of Pharmaceutical Investigation
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• 제22권2호
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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.

• 한국미생물·생명공학회지
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• 제20권4호
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• pp.422-429
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• 1992

Maltosy-$\beta$-cyclodextrin는 $\beta$-cyclodextrin에 maltose가 $\Alpha$-1,6 glycosidic bond로 결합된 분지환상결합체로서 pullulanase의 역반응(축합반응)을 이용하여 $\beta$-cyclodextrin과 maltose로부터 합성된다. Maltosyl-$\beta$-cycloextrin의 합성수율을 증가시키기 위하여 각종 water activity depressor인 각종 polyol, sugar 그리고 polyethylene glycol(PEG)등의 첨가의 영향을 검토하였다. 가장 적절한 water activity depressor는 PEG 6000로서, 첨가량 10%(w/w)의 경우 maltosyl-$\beta$-cyclodextrin 생성량과 합성수율은 크게 증가하여 3.02g/100ml 와 55.9%(w/w)로서, 첨가하지 않았을 경우보다 약 1.3배 증가하였다. Water activity는 PEG 6000을 20%(w/w) 첨가할 때 원래의 0.966에서 0.914로 감소하였으며, maltosyl-$\beta$-cyclodextrin 합성수율은 water activity에 반비례하여 증가하였다. Pullulanase의 역반응을 이용한 maltosyl-$\beta$-cyclodextrin 합성반응의 각종 열역학적 상수를 평가하였으며, $\Delta$H는 36.788kJ/mol, $\Delta$S는 0.067kJ/moleK, 그리고 $\Delta$G는 14.433kJ/mole이였다. PEG 6000의 분리회수에 적절한 ultrafiltration membrane의 pore size는 3K dalton이었으며, 여과액과 농축액의 적정 분획비는 1.0 : 9.0였다. Maltosyl-$\beta$-cyclodextrin 합성수율의 증가는 첨가한 PEG가 water activity를 감소시켜 합성된 maltosyl-$\beta$-cyclodextrin이 재분해되는 pullulanase이 정반응인 hydrolysis reaction을 억제하여 equilbrium state에 변화를 주기 때문인 것으로 유추된다.

• 공업화학
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• 제23권5호
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• pp.462-466
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• 2012

베타-사이클로덱스트린($\beta$-cyclodextrin, $\beta$-CD) 중합체(polymer)는 가교제인 epichlorohydrin (EPI)과 $\beta$-CD의 몰 비가 10 : 1으로, 강한 염기조건에서 합성하였다. 합성한 $\beta$-CD 중합체 내의 $\beta$-CD contents는 52%였다. 광, pH반응성 복합체를 제조하기 위해 신남산을 첨가하였고 첨가된 신남산은 소수성 상호작용에 의해 $\beta$-CD 공동에 포접되었다. 형성된 $\beta$-CD 중합체와 신남산 복합체를 투과전자현미경을 이용하여 관찰하였을 때 복합체의 형상을 관찰하였다. 광 조사에 따른 이량화도는 $\lambda$ = 365 nm의 UV조사 시 증가하였으며 $\lambda$ = 254 nm의 UV조사 시 감소하였다. 또한 동적 광 산란(dynamic light scattering)장치를 이용하여 측정한 복합체의 크기는 광 조사 유무에 따라 큰 변화가 측정 되지 않았고, pH 반응성을 관찰한 실험에서도 복합체의 크기와 제타 전위(zeta potential) 모두 pH에 따른 변화가 나타나지 않았다.

• 약학회지
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• 제42권1호
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• pp.59-69
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• 1998

To increase the solubility of quercetin, which is a practically insoluble flavonoid of Ginkgo biloba leaf, the effects of nonaqueous vehicles. Their cosolvents, water-sol uble polymers and modified cyclodextrins (CDs) were observed. Polyethylene glycols, diethyleneglycol monoethyl ether, and their cosolvents with water showed a good solvency toward quercetin. Also the aqueous solutions of povidone, copolyvidone and Cremophor RH 40 was effective in solubilizing quercetin. Complex formation of quercetin with ${\beta}$-cyclodextrin (${\beta}$-CD), dimethyl-${\beta}$-cyclodextiin (DMCD), 2-hydroxypropyl-${\beta}$-cyclodextrin (HPCD) and ${\beta}$-cyclodextrin sulfobutyl ether (SBCD) in water was investigated by solubility method at $37^{\circ}C$. The addition of CDs in water markedly increased the solubility of quercetin with increasing the concentration. AL type phase solubility diagrams were obtained with CDs studied. Solubilizaton efficiency by CDs was in the order of SBCD >> DMCD > HPCD > ${\beta}$-CD. The dissolution rates of quercetin from solid dispersions with copolyvidone, povidone and HPCD were much faster than those of drug alone and corresponding physical mixtures, and exceeded the equilibrium solubility (3.03${\pm}1.72{\mu}$g/ml). The permeation of quercetin through duodenal mucosa did not occur even in the presence of enhancers such as bile salts, but the permeation was observed when the mucus layer was scraped off. This was due to the fact that quercetin had a strong binding to mucin ($58.5{\mu}$g/mg mucin). However rutin was permeable to the duodenal mucosa. The addition of enhancer significantly increased the permeation of rutin in the order of sodium glycocholate.

• Journal of Pharmaceutical Investigation
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• 제25권1호
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• pp.31-36
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• 1995

Solid dispersions and inclusion complex were prepared for the enhancement of solubility and dissolution rate of poorly water-soluble ibuprofen(IPF) as a model drug. Polyethylene glycol 4000(PEG4000) and polyvinylpyrrolidone(PVP) were used for the preparation of solid dispersion. $2-Hydroxypropyl-{\beta}-cyclodextrin(2-HP{\beta}CD)$ was also used for the preparation of inclusion complex. The solubility of IPF increased as the concentration of PEG4000, PVP and $2-HP{\beta}CD$ increased. Solubilization capacity of $2-HP{\beta}CD$ was increased about 10 times when compared to PEG 4000 and PVP. The dissolution rate of drug from solid dispersions and inclusion complex in the simulated gastric fluid was enhanced when compared to pure IPF and commercial $BR4^{\circledR}$ tablet as a result of improvement of solubility. In case of solid dispersions, dissolution rate of drug was proportional to polymer concentration in the formulation. The marked enhancement of dissolution rate of drug by inclusion complexation with $2-HP{\beta}CD$ was noted. However, dissolution rate of drug from solid dispersions and inclusion complex in the simulated intestinal fluid was not significant because IPF was readily soluble in that condition. From these findings, water-soluble polymers and cyclodextrin were useful to improve solubility and dissolution rate of poorly water-soluble drugs. However, easiness and reliability of preparation method, scale-up and cost of raw materials must be considered for the practical application of solid dispersion and inclusion complex in pharmaceutical industry.