• 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.

• 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.

• 한국지하수토양환경학회:학술대회논문집
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• 한국지하수토양환경학회 2003년도 총회 및 춘계학술발표회
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• pp.120-123
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• 2003

Immobilization behavior of methyl tert-butyl ether (MTBE) by various cyclodextrins(CDs) was studied to investigate the feasibility of MTBE removal using cyclodexrins. Even though MTBE has relatively low hydrophobicity and higher polarity compared to other organics, it was effectively immobilized by CDs. The immobilization isotherms was shown as a type of Freundlich isotherms, and the immobilization capacity of -CDs was the largest among natural COs. The initial apparent association constant for MTBE-CD complex follows the order : gamma = beta > methyl-beta > hydroxypropyl beta > alpha. These differences of the constants are related to the size of MTBE and CDs. The size of beta-CD and gamma-CD is large to encapsulate MTBE molecule into the cavity, which that of alpha-CB is too small to encapsulate MTBE.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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• pp.302-302
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• 1994

오메프라졸의 산 불안정성을 개선하기 위하여 신규 합성한 오메프라졸 cholestyramin resin 염 복합체와 오메프라졸 hydroxypropyl-$\beta$-cyclodextrin (HP-$\beta$-CD) 포접화합물의 약효를 검색하였다. 생체외 실험 (in vitro test)으로 H$^{+}$/K$^{+}$-ATPase 활성도 저해효과를 검토하였으며 생체내 실험 (in vivo test)으로 Shay 결찰법에 의한 위산분비 억제효과에 대한 실험을 실시하였다. 오메프라종 염 복합체와 오매프라졸 포접화합물은 1$\times$$10^{-5}$-1$\times$$10^{-3}$M농도 범위에서 용랴의존적으로 H$^{+}$K$^{+}$-ATPase 활성을 억제시켰으며 $IC_{50}$/치는 오메프라졸 결과와 유사하였다. 셍체네 실험에서는 오메프라졸 HP-$\beta$-CD 포접화합물이 오메프라졸과 그 resin염복합체보다 위액분비량, 펩신 활성도에 대한 $IC_{50}$/치가 낮았으며 이는 생체내에서 포접 화합물이 오메프라졸의 안정성을 증가시킴으로서 위산분비 억제효과를 증가시킨것으로 사료된다.

• 대한화장품학회지
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• 제48권1호
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• pp.77-85
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• 2022

레틴알(RA)은 레티놀과 레티노익애씨드의 중간체로 비타민A 유도체이며 주름개선 효과가 우수하다. 본 연구에서는 drug-in-cyclodextrin-in-liposome (DCL)을 이용하여 레틴알의 안정성을 높였다. 레틴알과 hydroxypropyl-β-cyclodextrin (HP-β-CD) 복합체를 동결건조 방식으로 제조하였고, UV-Vis 분광법, FT-IR 및 SEM 이미지로 레틴알의 포접 여부를 확인하였다. 레틴알과 HP-β-CD의 비율이 1 : 15 (w/w)일 때 약 95.6% 포집되었다. 레틴알-HP-β-CD 복합체는 호모믹서 및 마이크로플루다이저로 리포좀에 담지시켰으며, 평균 입자 크기는 215.3 ± 4.2 nm, 제타포텐셜 -33.2 ± 1.5 mv로 나타났다. 레틴알의 분해 안정도 평가에서, 물에서 레틴알-HP-β-CD-리포좀의 레틴알 감소율은 1.8%로 레틴알-리포좀(5.8%), 레틴알-HP-β-CD복합체(9.7%), 레틴알 단독(37.6%)보다 높게 나타났다. 레틴알-HP-β-CD-리포좀이 함유된 크림(0.05% RA 함유)을 제조하여, 미간, 이마, 목, 눈가, 입가, 팔자 주름개선 효능 및 피부 치밀도를 2 ~ 4 주간 평가하였다. 그 결과 레틴알크림은 피부 자극 없이 유의한 주름 개선 효과를 보였다. 결론적으로, DCL시스템을 이용한 이중 안정화 기술은 레틴알의 안정화를 높여 피부 주름 개선 효과에 기여함을 확인하였다.

• 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.

• 대한화장품학회지
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• 제33권1호
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• pp.1-6
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• 2007

일반적으로 cyclodextrin (CD)은 liposome의 구조를 불안정하게 만드는 것으로 알려져 있다. 본 연구에서는 양친매성 고분자전해질을 리포좀에 도입하여 CD에 대한 리포좀의 안정도를 증진시키는 연구를 수행하였다. Transmission electron microscopy와 photocorrelation spectroscopy 결과들로부터 ${\beta}-CD$ (${\beta}CD$)와 hydroxypropyl-${\beta}CD$ ($HP{\beta}CD$)를 함유하는 리포좀에 고분자가 도입되었을 때 CD를 함유하는 phosphatidylcholine (PC)-cholesterol (Chol) 리포좀보다 우수한 구조적 안정성을 나타내었다. 또한, rhaponticin (Rh)을 $HP{\beta}CD$에 포접시키고 이를 함유하는 PC-Chol 리포좀과 고분자가 도입된 리포좀의 안정도를 비교해 보았을 경우도 마찬가지로 고분자가 도입된 리포좀이 월등히 향상된 구조적인 안정성을 나타내는 것을 확인하였다. 이와 더불어 guinea pig의 피부조직을 사용하고 franz-cell을 통한 in vitro 피부흡수실험을 수행한 결과, $HP{\beta}CD$에 의해 가용화된 Rh의 피부흡수가 고분자가 도입된 리포좀에 의해 증진됨을 확인할 수 있었다. 상기 결과들은 양친매성 고분자 전해질의 도입에 따라 CD에 의해 가용화된 특정한 활성성분을 함유하는 리포좀의 구조적인 안정성을 효과적으로 증진시킬 수 있음을 확인시켜 주었으며, 이렇게 향상된 리포좀의 구조적인 안정성을 통해 약물전달시스템 측면에서 많은 응용이 가능할 것으로 생각된다.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1997년도 춘계학술대회
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• pp.118-118
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• 1997

Solid dispersions were used to increase the dissolution rate of biphenyl dimethyl dicarboxylate (DDB) in water, with the ultimate goal of optimizing its bioavailability when incoporated into pharmaceuticals. Carriers used were Kollidon 30, Kollidon VA 64, 2-hydroxypropyl-${\beta}$-cyclodextrin (HPCD), sodium salicylate or sodium benzoate. DDB solid dispersions were prepared at drug to carrier proportions ranging from 1 : 5 to 1 : 20 (w/w) by solvent evaporation method. DDB tablets (7.5 mg) were prepared by compressing the powder mixture composed of solid dispersions, lactose, corn starch, crospovidone and magnesium stearate using a single-punch press. DDB capsules (7.5 mg) were prepared by filing the mixture into empty hard gelatin capsules (size #1). Dissolution studies of DDB from powdered solid dispersions, tablets and capsules were performed in 900 $m\ell$ of water at 100 rpm and 37$^{\circ}C$ by the paddle method. The dissolved amount was assayed by HPLC and expressed as the mean(%)of three determinations.

• Journal of Pharmaceutical Investigation
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• 제31권1호
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• pp.27-35
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• 2001

To evaluate the site-specific permeation of aspalatone (acetylsalicylic acid maltol ester, AM) through gastrointestinal tract, the enzymatic degradation and permeation studies were carried out using gastric, duodenal and jejunal mucosae of rabbits. It was found that $15.2{\pm}11.4%$, $11.6{\pm}5.2$ and $0.8{\pm}0.6%$ of the donor dose of AM, salicylmaltol (SM) and aspirin (ASA) permeated through the upper gastric mucosa after 8 hr of permeation, respectively. After 8 hr of AM permeation, SM and ASA were measured to be $15.0{\pm}1.7$ and $2.6{\pm}0.8%$ of the dose in the donor solutions, respectively, and salicylic acid (SA) was not detected even after 6 hr, suggesting a very low gastric damage. For the gastric mucosa, the increase of donor dose from 100 to $1,000\;{\mu}g/ml$ increased the permeation flux dose-dependently (r=0.9905). For the duodenal and jejunal mucosae, however, AM was fully degraded into SM and SA due to the esterase activities within 30 min. AM and ASA were not detected in the receptor solution. This result indicates that AM is not a prodrug of ASA. Addition of potassium fluoride (0.5%) into the donor solution delayed the degradation of AM, but did not allow the permeation through duodenal mucosa even by the inhibition of esterase activity. The addition of $dimethyl-{\beta}-cyclodextrin$ and $2-hydroxypropyl-{\beta}-cyclodextrin$ (5%) into the donor solutions also did not show favorable effects on the permeation of AM through various mucosae. In comparison of permeation rates of AM and ASA through the upper gastric mucosa, the flux of ASA was 4.2 times faster than AM based on the molar concentration. ASA also was fully degraded in the donor solutions faced with duodenal and jejunal mucosae within 2 hr, and was not detected in the receptor solution, suggesting a slower metabolism compared with AM.

• KSBB Journal
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• 제22권5호
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• pp.328-335
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• 2007

본 연구에서는 뛰어난 주름개선효능을 가지고 있지만 수용액상에서의 낮은 용해도로 인해 사용에 제약이 있는 UA의 용해도를 향상시키기 위하여 HP-$\beta$-CD와의 포접체를 형성하는 UA함유 제제를 제조하고자 하였으며 특히 초임계유체 공정기술을 포접화합물 제조에 도입하여 초임계 기술의 적용의 가능성을 조사하였다. UA의 용해도를 증가시키기 위한 제조방법으로 HP-$\beta$-CD와의 혼합물을 반죽법, 용매증발법 및 초임계유체공정을 이용하여 제조하고, 각 제조시료들의 용해도 증가 및 특성을 확인한 결과 용매증발법과 초임계 ASES공정에 의해 물에 대한 용해도가 증가된 UA/HP-$\beta$-CD 제제를 얻을 수 있었다. 각 방법에 의해 제조된 UA 함유 제제의 화장품 제형에서의 안정도 실험을 수행하였으며 실험결과 유화제형에서는 모든 제제가 시간 및 온도에 대한 안정성을 보였으나 가용화제형에서는 ASES 제제와 Ursolisome 제제의 경우 시간이 경과하거나 함유 UA농도가 증가함에 따라 화장품 제형의 현탁도가 증가함을 확인할 수 있었다.