• Journal of Pharmaceutical Investigation
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• v.27 no.4
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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.

• 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.

• Journal of Pharmaceutical Investigation
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• v.23 no.1
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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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• v.24 no.4
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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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• v.27 no.3
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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.

• Clean Technology
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• v.19 no.3
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• pp.212-218
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• 2013

The microparticles of 2-hydroxypropyl-${\beta}$-cyclodextrin (HP-${\beta}$-CD) were prepared using aerosol solvent extraction system (ASES) by employing supercritical carbon dioxide as an antisolvent, The effects of various process parameters such as temperature, pressure, solution concentration and solution flow rate on the formation of HP-${\beta}$-CD microparticles were investigated. The HP-${\beta}$-CD microparticles prepared by the ASES process were observed to consist of agglomerates of nano-sized (50-200 nm) particles. When an aqueous solution of ethanol was used as a solvent for HP-${\beta}$-CD, the HP-${\beta}$-CD particles were found to be spherical in shape and to become larger as the water content increased. It was confirmed that the micronization of HP-${\beta}$-CD using the ASES process could enhance the inclusion efficiency of ibuprofen/HP-${\beta}$-CD complexes significantly.

• Archives of Pharmacal Research
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• v.26 no.2
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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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• v.43 no.1
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• pp.110-117
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• 2005

In this work, solid-state inclusion complex powders of itraconazole and $2-hydroxypropyl-{\beta}-cyclodextrin(HP-{\beta}-CD)$ were produced by a supercritical anti-solvent (SAS) process. In order to evaluate the degree of complexation, the thermal behavior of the microparticulate complexes was investigated using differential scanning calorimetry. The experimental results obtained for the solubility and dissolution rate of the microparticulate inclusion complexes in a buffer solution of pH 1.2 showed that the complexation of itraconazole with $HP-{\beta}-CD$ results in a significant increase in the solubility and dissolution rate of itraconazole. The particle size of the SAS-produced inclusion complexes was dramatically reduced ($<0.1-0.5{\mu}m$) compared with untreated itraconazole ($30-50{\mu}m$) and $HP-{\beta}-CD$ ($50-100{\mu}m$). The solubility of itraconazole was increased with the increase of pressure at a constant temperature to ca. $758.6{\mu}g/mL$ in an aqueous medium of pH 1.2. The dissolution rate of itraconazole was observed to be significantly improved and about 90% of itraconazole was found to be dissolved within 5-10 min.

• Archives of Pharmacal Research
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• v.20 no.6
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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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• v.19 no.4
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• pp.321-326
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• 2004

Microparticles of an inclusion complex between itraconazole and 2-hydroxypropyl-${\beta}$-cyclodextrin (HP-${\beta}$-CD) were prepared using an environmentally-benign supercritical anti-solvent (SAS) process. In order to evaluate the degree of complexation, the thermal behavior of solid micro particulate complexes was investigated using differential scanning calorimetry. The experimental results obatined for the solubility and dissolution rate of the microparticulate inclusion complexes in a buffer solution of pH 1.2 showed that the complexation of itraconazole with HP-${\beta}$-CD results in a significant increase in the solubility and dissolution rate of itraconazole. For the microparticulate itraconazole/Hp-${\beta}$-CD inclusion complexes prepared by the SAS process, about 80% of itraconazole was found to dissolve in the buffer solution. Our experimental results confirmed that the SAS process is a promising method for the preparation of microparticles of water-insoluble drug/cyclodextrin inclusion complexes.