• Journal of Pharmaceutical Investigation
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• 제34권2호
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• pp.131-138
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• 2004

This study was aimed to investigate the feasibility of nasal delivery of caffeine for the elimination of sleepiness. The effects of various vehicles, solubilizers, and enhancers on the permeation of caffeine through rabbit nasal mucosa was observed. The permeation study was carried out using a Franz-type permeation system at $37^{\circ}C$, and the amount of caffeine permeated though the rabbit nasal mucosa was determined by a validated HPLC. The apparent solubility and phys iochemical stability of caffeine in various nasal formulations were was determined. The effect of hydrotropes and modified cyclodextrins on the solubility of caffeine in water was determined by equilibrium solubility method. The solubility of caffeine in water was 29 mg/mL at $30^{\circ}C$. The addition of sodium benzoate and nicotinamide at 10% improved the solubility of caffeine (115 and 132 mg/mL, respectively) in aqueous solution. The flux of caffeine though the nasal mucosa from aqueous solution was $2.1{\pm}0.26\;mg/cm^2/hr$. The addition of sodium benzoate reduced its permeation $(1.4{\pm}0.01\;mg/cm^2/hr)$, but sodium benzoate with 5% $2HP{\beta}CD$ and 0.03% monoterpenes increased its permeation $(2.4{\pm}0.04\;mg/cm^2/hr)$ markedly. The addition of nicotinamide also increased also increased its permeation $(2.5{\pm}0.36\;mg/cm^2/hr)$. markedly. As the concentration of caffeine in nasal formulation increased, the permeation flux increased linearly. Caffeine was stable physicochemically and enzymatically in the nasal mucosa extract at $37^{\circ}C$. These results suggest that caffeine can be efficiently delivered nasally and the development of nasal formulation will be feasible.

• 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.