• YAKHAK HOEJI
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• v.42 no.1
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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.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.116-116
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• 1997

Complex formation of practically insoluble dexamethasone dipropionate (DDP) with ${\beta}$-cyclodextrin (${\beta}$-CD), dimethyl-${\beta}$-cyclodextrin (DMCD), trimethyl-${\beta}$-cyclodextrin (TMCD), 2-hydroxypropyl-${\beta}$-cyclodextrin (HPCD) and sulfobutyl ether ${\beta}$-cyclodextrin (SBCD) in water was investigated by solubility method at various temperatures. Water solubility of DDP was found to be 1.78 $\mu\textrm{g}$/$m\ell$ at 37$^{\circ}C$. Propylene glycol (PG)-water cosolvent increased the solubility of DDP, but the solubilization was not sufficient (8.93 $\mu\textrm{g}$/$m\ell$ in 20% PG). The addition of CD markedly increased the solubility of DDP in water, and A$\sub$L/ type phase solubility diagrams were obtained with ${\beta}$-CD, TMCD, HPCD and SBCD, where the apparent stability constants of the soluble complexes at 25$^{\circ}C$ were determined to be 1388, 216, 1054, and 1992 M$\^$-1/, respectively. However, DMCD remarkably increased the solubility of DDP, and showed an A$\sub$P/ type diagram, suggesting that DMCD forms a soluble complex of high order with DDP. The stability constant for the DDP-DMCD complex at 25$^{\circ}C$ was determined to be 19132 M$\^$-1/. The thermodynamic parameters were calculated for the inclusion complex formation in aqueous solution. CD (1${\times}$10$\^$-2/M) remarkably decreased the partition coefficients of DDP between isopropyl myristate/water in the order of TMCD < ${\beta}$-CD < HPCD < SBCD < DMCD, and in squalane/water system in the order of HPCD < TMCD < ${\beta}$-CD < DMCD < DMCD $\leq$ SBCD. This finding represents that, in a o/w type cream, cyclodextrin complexation with DDP may result in high concentration of DDP in aqueous phase. The permeation of DDP through a cellophane membrane was highly suppressed by the addition of CD, and the degree of suppression was different among CDs, indicating that CD may control the skin permeation of DDP. The dissolution rates of solid dispersions with CDs were much faster than those of drugs alone and corresponding physical mixtures. All DDP-CD solid dispersions exceeded the equilibrium solubility. Consequently these results suggest that complex formation of DDP with CDs may provide useful means to markedly enhance the solubility, and CDs are useful in the semi-solid preparations such as creams and gels for topical application.

• Journal of Pharmaceutical Investigation
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• v.39 no.2
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• pp.97-106
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• 2009

Although lovastatin (LS) is widely used in the treatment of hypercholesterolemia, its bioavailability is known to be around 5%. This study was aimed to increase the solubility and dissolution-permeation rates of LS using solid dispersions (SDs) with bile salts. The solubilities of LS in water, aqueous bile salt solutions and non-aqueous vehicles were determined, and effects of bile salts on the cellulose or duodenal permeation of LS from SDs were evaluated using a horizontal permeation system. SDs were prepared at various ratios of LS to carriers, such as sodium deoxycholate (SDC), sodium glycocholate (SGC) and/or 2-hydroxypropyl-$\beta$-cyclodextrin (HPCD). The addition of bile salts (25 mM) in water increased markedly the solubility of LS by the micellar solubilization. Some non-aqueous vehicles were effective in solubilizing LS. From differential scanning calorimetric studies, it was found that the crystallinity of LS in SDs disappeared, indicating a formation of amorphous state. The SDs showed markedly enhanced dissolution compared with those of their physical mixtures (PMs) and drug alone. In the dissolution-permeation studies using a cellulose membrane, the donor and receptor solutions were maintained as a sink condition using pH 7.0 phosphate buffer containing 0.05% sodium lauryl sulfate (SLS). The flux of LS alone was nearly same as that of LS-SDC-HPCD (1:3:6) PM. However, the flux of LS-SDC-HPCD (1:3:6) SD slightly increased compared with drug alone and PM, suggesting that entrapment of LS in micelles does not significantly hinder the permeation across cellulose membrane. In the dissolution-duodenal permeation studies using a LS-HPCD-SDC (1:3:6) SD, the addition of various bile salts in donor solutions (25 mM) enhanced the permeation of LS markedly, and the fluxes were found to be $0.69{\pm}0.41$, $0.87{\pm}0.51$, $0.84{\pm}0.46$, $0.47{\pm}0.17$ and $0.68{\pm}0.32{\mu}g/cm^2/hr$ for sodium cholate (SC), SDC, SGC, sodium taurodeoxycholate (STDC) and sodium taurocholate (STC), respectively. The stepwise increase of donor SGC concentration increased the flux dose-dependently. From the relationship of donor SGC concentration and flux, the concentration of SGC initiating the permeation across the duodenal mucosa was calculated to be 11.1 mM, which is nearly same as the critical micelle concentration (CMC, 11.6 mM) of SGC. However, with no addition of bile salts and below CMC, the permeation was very limited and irratic, indicating that LS itself is very poor permeable. Higher protions of bile salt in SD such as LS-SDC or LS-SGC (1 : 49 and 1 : 69) showed highly promoted fluxes. In conclusion, SD systems with bile salts, which may form their micelles in intestinal fluids, might be a promising means for providing enhanced dissolution and intestinal permeation of practically insoluble and non-absorbable LS.

• Journal of Korean Society of Forest Science
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• v.89 no.1
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• pp.65-76
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• 2000

Lichen flora of 'Backwoon' mountain, Korea, was investigated during the summer of 1998 and 1999 to screen out lichen species which can be used as a biomonitor for atmospheric ozone. The identified foliose or fructicose lichens in the area were classified into 9 families, 20 genera and 34 species. The dominant lichen species in the area were found to be Leptogium sp., Parmelia sp., Parmotrema sp., Phaeophyscia sp. and Cladonia sp. It was also found that lichen species showing a wide range of sensitiveness to air pollution were distributed in 'Backwoon' mountain. The Parmotrema austrosinense, P. tinctorum, Certrelia braunsiana and Ramalina yasudae collected in the area were exposed to ozone at the level of 200ppb, 8hr/day in controlled growth chamber for 2 weeks. Malondialdehyde(MDA), hydroperoxy conjugated dienes(HPCD), soluble protein content and OD435nm/OD415nm ratio for phaeophytinization of chlorophyll were measured and a pollution index(PI) was calculated for each lichen. Ozone exposure severely damaged to the lichens in the order of P. austrosinense>P. tinctorum>C. braunsiana>R. yasudae. P. austrosinens easily identified and widely distributed in Korea is likely to be a very useful biomonitor of air pollution, especially for ozone. These results indicate that Korean lichen species can be used as a biomonitor for air pollution to evaluate air quality contaminated with ozone.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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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.

• Korean Journal of Veterinary Research
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• v.18 no.2
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• pp.61-67
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• 1978

The detection of Bordetella bronchiseptica which is supposed to be an agent of the infectious atrophic rhinitis of swine, is likely to receive more attention in the future as the pork industry comes to realize that eradication of this infection from breeding herds is a practical possibility. Experiments described here were carried out to establish the rapid plate agglutination test for the detection of the infectious atrophic rhinitis of swine in the field using the criteria of antigen preparation, effects on the antigenecity after storing of the antigen and reaction appearing time. Also, the agglutinabilities between the plate and tube method were compared and the degree of pathological lesions were recorded in relation to tube agglutination titers. Obtained results were as follows: 1. No differences were noted in the agglutinabilities on the plate agglutination test between the treatments in antigen preparation-formolized, merthiolate-killed and living organism. 2. The agglutinability of the antigens did not show any significant changes until 10 weeks of storage at 4 C; however, after 10 weeks of storage, non-specific reaction was observed with the HPCD control sera. 3. The results of the plate and tube agglutination tests were not comparable but the effective use of the plate method in Bordetella bronchiseptica eradication programs in pigs especially in the sow is stressed as a screening test.

• Journal of Soil and Groundwater Environment
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• v.23 no.6
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• pp.46-53
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• 2018

Mobility reduction of 2,4,6-trinitrotoluene (TNT) was tested by amending monopotassium phosphate (MKP) and montmorillonite to a firing range soil contaminated with TNT. While addition of MKP enhanced sorption of TNT on soil matrix, and combined use of MKP with montmorillonite significantly decreased desorption of TNT as well as remarkably increased the TNT sorption. Montmorillonite amendment by 5% of soil mass resulted in TNT desorption of 0.12 mg/kg from soil loaded with 9.93 mg/kg-TNT. The decrease of TNT desorption was proportional to the amount of montmorillonite amended. At 10 and 15% amendment, only 0.79 and 1.23 mg/kg-TNT was desorbed from 29.33 and 48.80 mg/kg-TNT. In addition, the leaching of TNT with synthetic precipitation leaching procedure (SPLP) and hydroxypropyl-${\beta}$-cyclodextrin (HPCD) decreased, indicating that TNT in MKP/montmorillonite-treated soil became more stable and less leachable. The results demonstrate that addition of MKP and montmorillonite to TNT-contaminated soil reduces the mobility of TNT from soil not only by increasing TNT sorption, but also decreasing TNT desorption. It was found that MKP and montmorillonite amendments by 5 and 10% of soil mass, respectively, were optimal for reducing the mobility of soil TNT.