• Journal of Pharmaceutical Investigation
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• 제27권4호
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• pp.295-301
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• 1997

Nitrendipine, a slightly soluble calcium channel blocking agent forms a solid dispersion system with $hydroxypropyl-{\beta}-cyclodextrin$, which exhibits better dissolution characteristics than the uncomplexed drug. The dissolution rate of nitrendipine was markedly increased in solid dispersion system in pharmacopeial disintegration media at pH 1.2 and pH 6.8. Four different dosage forms of nitrendipine were administered to rats: (a) nitrendipine in the solution of PEG 400; (b) nitrendipine solid dispersion system with $hydroxypropyl-{\beta}-cyclodextrin$ in a molar ratio of 1:2 by solvent evaporation method and administered in capsule form; (c) physical mixture of nitrendipine with $hydroxypropyl-{\beta}-cyclodextrin$ in a molar ratio of 1:2 and administered in capsule form; (d) nitrendipine alone administered in capsule form. Relative bioavailability after the oral administration of various dosage forms to rats with a dose of 10 mg/kg equivalent to nitrendipine was compared with that of nitrendipine in the solution of PEG 400. The AUC of solid dispersion was significantly bigger than that of nitrendipine powder. $T_{max}$ of solid dispersion was significantly shorter and $C_{max}$ was higher than that of nitrendipine powder. These results indicate that the bioavailability of nitrendipine could be improved markedly by inclusion complexation. An interesting correlation also appears to exist between the in vitro dissolution data and the area under the plasma concentration-time curves.

• 폴리머
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• 제38권3호
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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.

• Journal of Pharmaceutical Investigation
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• 제23권1호
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• pp.11-18
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• 1993

Inclusion complex of ibuprofen with $2-Hydroxypropyl-{\beta}-cyclodextrin\;(HP-{\beta}-CD)$ in aqueous solution and in the solid state was evaluated by the solubility method and the instrumental analysis such as infrared spectroscopy, thermal analysis and x-ray diffractometry. The aqueous solubility of ibuprofen was increased linearly with the increase in the concentration of $HP-{\beta}-CD$, showing an $A_L$ type phase solubility diagram. The results showed that the dissolution rate of ibuprofen was significantly increased by complexation with $HP-{\beta}-CD$. $Ibuprofen-HP-{\beta}-CD$ complex enhanced the mean plasma concentration levels and the area under plasma concentration-time curve after oral administration compared to those of the drug alone. It is concluded that the complex of ibuprofen with $HP-{\beta}-CD$ increases the dissolution rate and improves the bioavailability of the ibuprofen by the formation of a water-soluble complex.

• Archives of Pharmacal Research
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• 제24권4호
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• pp.281-285
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• 2001

Enantiomers of five racemic ${\beta}_2$-agonists were investigated by capillary electrophoresis employing a hydroxypropyl-${\beta}$-cyclodextrin (HP-${\beta}$-CD). The effects of the concentration of HP-${\beta}$-CD added to the background electrolyte and of the pH of the buffer on the effective mobility and resolution of the studied compounds were examined. Very good resolution was achieved for terbutaline and clenbuterol; salbutamol and bambuterol was able to be partially resolved. Enantioselectivity and resolution were influenced by the concentration of the HP-7-CD, buffer composition and pH.

• Journal of Pharmaceutical Investigation
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• 제27권3호
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• pp.165-171
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• 1997

Ibuprofen, a nonsteroidal antiinflammatory, analgesic and antipyretic drug, has several limitations in clinical application because of low solubility in water and gastrointestinal irritation. Effect of ibuprofen/$2-Hydroxypropyl-{\beta}-cyclodextrin\;(HP{\beta}CD)$ inclusion compound on release of suppository was investigated. Complex formation was confirmed by $^{1}H-\;and\;^{13}C-NMR$ spectroscopy. The release of ibuprofen from suppository base in vitro was significantly increased by the complexation with $HP{\beta}CD$. The release of ibuprofen from hydrophilic base was faster than that from hydrophobic base. In vivo studies, the release rate of ibuprofen from suppository was accelerated after rectal administration in complex form. This results suggested that ibuprofen/$HP{\beta}CD$ complex can be practically used for suppository to have faster effect of ibuprofen with reduced side effect.

• 청정기술
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• 제19권3호
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• pp.212-218
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• 2013

초임계 이산화탄소를 역용매로 이용하는 aerosol solvent extraction system (ASES) 방법을 사용하여 HP-${\beta}$-CD 미립자를 제조하였으며, 공정변수가 입자의 크기와 형태에 미치는 영향을 조사하였다. 또한, 초임계 이산화탄소를 이용하여 이부프로펜과 HP-${\beta}$-CD의 포접복합체를 제조하였으며, ASES 공정에 의해 변형된 HP-${\beta}$-CD의 입자 형상이 포접효율에 미치는 영향에 대해 고찰하였다. ASES 공정으로 제조된 HP-${\beta}$-CD 미립자는 50~200 nm 크기의 나노 입자들이 응집된 입자 형상을 나타내었다. 에탄올 수용액을 HP-${\beta}$-CD의 용매로 사용한 경우 구형의 입자가 제조되었으며, 물의 양이 증가함에 따라 입자의 크기가 증가하였다. 초임계 이산화탄소를 이용해 고체상태에서 이부프로펜/HP-${\beta}$-CD 포접복합체를 제조하는 경우 초임계 ASES 방법에 의한 미세입자화 공정을 통해 포접효율을 향상시킬 수 있는 가능성을 확인하였다.

• Archives of Pharmacal Research
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• 제26권2호
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• pp.120-123
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• 2003

A method for the determination of terbutaline enantiomers in human urine by capillary elctrophoresis has been developed. Optimum resolution was achieved using 50 mM phosphate buffer, pH 2.5, containing 15 mM of hydroxypropyl-$\beta$-cyclodextrin as a chiral selector. Urine samples were prepared by solid-phase extraction with Sep-pak silica, followed by CE. The assay was linear between 2-250 ng/mL (R = 0.9998 for (S)-(+)-terbutaline and R = 0.9999 for (R)-(-)-terbutaline) and detection limit was 0.8 ng/mL. The intra-day variation ranged between 6.3 and 14.5% in relation to the measured concentration and the inter-day variation was 8.2-20.1%. It has been applied to the determination of (S)-(+)-terbutaline and (R)-(-)-terbutaline in urine from healthy volunteer dosed with racemic terbutaline sulfate.

• Korean Chemical Engineering Research
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• 제43권1호
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• pp.110-117
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• 2005

초임계유체를 이용한 공정을 통하여 물에 대해 난용성 성질을 지니는 약물인 itraconazole과 $2-hydroxypropyl-{\beta}-cyclodextrin(HP-{\beta}-CD)$의 포접복합체를 제조하였다. 제조된 포접복합체는 SEM, DSC, XRD 등을 이용하여 고체상태의 특성 분석을 수행하여 itraconazole의 결정성적 특성이 $HP-{\beta}-CD$와의 포접체를 형성하며 무정질적으로 변화된 것을 확인할 수 있었다. pH 1.2의 인공위액을 이용하여 수행된 수용액 내에서의 포접복합체의 용해도 및 용출시험 결과 itraconazole 원재료에 비하여 20-200배 정도의 증가된 용해도 결과를 얻을 수 있었다. 초임계유체 공정을 통하여 얻어진 포접복합체의 용해도는 압력증가에 의한 이산화탄소 밀도 증가에 따라 증가하였으며 동일 조건에서 용액 중의 $HP-{\beta}-CD$의 함량이 높아질수록 증가하였다. $35^{\circ}C$, 140 bar의 공정 조건에서 itraconazole과 $HP-{\beta}-CD$의 구성 몰비가 1:3인 용액을 사용하였을 경우 itraconazole 원재료에 비하여 약 200배 이상의 용해도인 $758.6{\mu}g/mL$의 용해도를 지니는 포접복합체를 얻을 수 있었다. 용출시험 결과 투입 약물의 90% 이상이 용출 개시 5-10분 내에 용출되어 대조제로 사용한 시판제제 및 원재료에 비하여 매우 빠른 초기 방출률과 우수한 용출 특성을 확인할 수 있었다. 본 연구를 통하여 기존의 시간소비성 및 다단계의 포접체 제조공정을 개선할 수 있는 한 방법으로 초임계유체 공정이 적용될 가능성을 확인할 수 있었다.

• Archives of Pharmacal Research
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• 제20권6호
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• pp.560-565
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• 1997

The physicochemical properties of melatonin (MT) in propylene glycol (PG) and 2-hydroxypropyl-.betha.-cyclodextrin $(2-HP{\beta}CD)$ vehicles were characterized. MT was endothermally decomposed as determined by differential scanning calorimetry (DSC). Melting point and heat of fusion obtained were $116.9{\pm}0.24^{\circ}C $.and $7249{\pm}217 cal/mol$., respectively. MT as received from a manufacture was very pure, at least 99.9%. The solubility of MT in PG solution increased slowly until reaching 40% PG and then steeply increased. Solubility of MT increased linearly as concentration of $2-HP{\beta}CD$ without PG INCREASED$(R^2=0.993)$. MT solubility in the mixtures of pg and $2-HP{\beta}CD$ also increased linearly but was less than the sum of its solubility in $2-HP{\beta}CD$ and PG individually. The MT solubility was low in water, simulated gastric or intestinal fluid but the highest in the mixture of PG(40v/v%) and $2-HP{\beta}CD$ (30w/v%) although efficiency of MT solubilization in $2-HP{\beta}CD$ decreased as the concentration of PG increased. MT was degraded in a fashion of the first order kinetics $(r^2>0.90)$. MT was unstable in strong acidic solution (HCl-NaCl buffer, pH 1.4) but relatively stable in other pH values of 4-10 at $70^{\circ}C$. In HCl-NaCl buffer, MT in 10% PG was more quickly degraded and then slowed dpwm at a higher concentration. However, the degradation rate constant of MT in 2-HP.betha.CD was not changed significantly when compared to the water. The current studies can be applied to the dosage formulations for the purpose of enhancing percutaneous absorption or bioavailability of MT.

• KSBB Journal
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• 제19권4호
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• pp.321-326
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• 2004

본 연구에서는 초임계 이산화탄소를 이용한 SAS 공정을 난용성 약물인 이트라코나졸과 친수성 물질인 HP-$\beta$-CD의 포접복합체 미세입자의 제조에 적용하기 위한 기초 연구를 수행하였다. 이트라코나졸과 HP-$\beta$-CD를 1:2의 몰비로 혼합한 용액을 사용하여 35∼$65^{\circ}C$의 온도범위와 83∼140 bar의 압력범위에서 SAS 공정으로 이트라코나졸/HP-$\beta$-CD 포접복합체 미세입자를 제조하였으며, 이트라코나졸 및 HP-$\beta$-CD 원재료의 열적 특성과 비교함으로써 초임계 유체 공정에 의해 포접복합체를 제조할 수 있음을 확인하였다. 또한, SAS 공정에 의해 제조된 이트라코나졸/HP-$\beta$-CD 포접복합체의 인공위액에 대한 이트라코나졸의 용출시험을 수행한 결과 이트라코나졸 원재료와 이트라코나졸을 함유한 대표적 시판 제제인 스포라녹스 캡슐제와 비교해 투입된 이트라코나졸의 50∼80%에 해당하는 양이 용출개시 5분 만에 방출되는 매우 빠른 초기 용출특성을 보임을 확인할 수 있었다. 이트라코나졸 /HP-$\beta$-CD 포접복합체의 제조시 SAS 공정 조건이 35$^{\circ}C$에서 $65^{\circ}C$로 높아짐에 따라 이트라코나졸의 용출률이 감소하였을 뿐만 아니라 열분석 결과 이트라코나졸의 용융 피크의 세기도 점차로 증가하게 된다는 결과로부터 포접복합체의 형성이 이루어지는 주변 매질의 온도가 높아짐에 따라 초임계 이산화탄소 분자의 활동도가 증가하게 되어 이트라코나졸과 HP-$\beta$-CD의 포접복합체 형성에 필요한 결합력이 점차로 약해져서 포접 효율이 저하하게 됨을 확인할 수 있었다.