• 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.

• Food Science and Preservation
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• v.18 no.2
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• pp.208-211
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• 2011

Limonoids are abundant as bitter taste in citrus fruit and other plants. Interestingly. limonoid UDP-glucosyltransferase (LUGT) effectively ameliorates the bitterness from limonoid. The high level of LUGT expression in Escherichia coli can result in the formation of insoluble aggregates known as inclusion bodies. We isolated the soluble LUGT protein when this inclusion body was renaturated with ${\beta}$-cyclidextrin treatment after protein denaturation by urea. Our present results suggest that the isolation of LUGT from inclusion body in cells leads to shed light to characterize the enzyme for food industry purposes.

• Proceedings of the Membrane Society of Korea Conference
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• 1998.06a
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• pp.135-153
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• 1998

Nanofiltration (NF) is a recently introduced term in membrane separation. In 1988, Eriksson was one of the first authors using the word 'nanofiltration' explicitly. Some years before, FilmTech started to use this term for their NF50 membrane which was supposed to be a very loose reverse osmosis membrane or a very tight ultrafiltration membrane. Since then, this term has been introduced to indicate a specific boundary of membrane technology in between ultrafiltration and reverse osmosis. The application fields of the NF membranes are very broad as follows: Demeneralizing water, Cleaning up contaminated groundwater, Ultrapure water production, Treatment of effleunts containing heavy metals, Offshore oil platforms, Yeast production, Pulp and paper mills, Textile production, Electroless copper plating, Cheese whey production, Cyclodextrin production, Lactose production. The earliest NF membrane was made by Cadotte et al, using piperazine and trimesoyl chloride as monomers for the formation of polyamide active layer of the composite type membrane. They coated very thin interfacially potymerized polyamide on the surface of the microporous polysulfone supports. The NF membrane exhibited low rejections for monovalent anions (chloride) and high rejections for bivalent anions (sulphate). This membrane was called NS300. Some of the earliest NF membranes, like the NF40 membrane of FilmTech, the NTR7250 of Nitto-Denko and the UTC20 and UTC60 of Toray, are formed by a comparable synthesis route as the NS300 membrane. Commercially available NF membranes nowadays are as follows: ASP35 (Advanced Membrane Technology), MPF21; MPF32 (Kiryat Weizmann), UTC20; UTC60; UTC70; UTC90 (Toray), CTA-LP; TFCS (Fluid Systems), NF45; NF70 (FilmTec), BQ01; MX07; HG01; HG19; SX01; SX10 (Osmonics), 8040-LSY-PVDI (Hydranautics), NF CA30; NF PES 10 (Hoechst), WFN0505 (Stork Friesland). The typical ones among the commercially available NF membranes are polyamide composite membrane consisting of interfacially polymerized polyamide active layer and microporous support. While showing high water fluxes and high rejections of multivalent ions and small organic molecules, these membranes have relatively low chemical stability. These membranes have low chlorine tolerance and are unstable in acid or base solution. This chemical instability is appearing to be a big obstacle for their applications. To improve the chemical stability, we have tried, in this study, to prepare chemically stable NF membranes from PVA. The ionomers and interfacially polymerized polyamide were used for the modification of'the PVA membranes. For the detail study of the active layer, homogeneous NF membranes made only from active layer materials were prepared and for the high performance, composite type NF membranes were prepared by coating the active layer materials on microporous polysulfone supports.

• Journal of Animal Science and Technology
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• v.52 no.3
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• pp.199-204
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• 2010

The objective of this study was to evaluate the effect of the different types and levels of prebiotics on intestinal microflora and fermentation products in the in vitro fermentation model. The prebiotcs used in this study were IMO (iso-malto oligosaccharide), CI (partially digested chicory-inulin), RA (raffinose) and CD (cyclodextrin). Experimental diet for growing pigs was predigested by digestive enzymes and this hydrolyzed diet was mixed with buffer solution containing 5% fresh swine feces. Then, the mixture was fermented with or without prebiotics at the concentrations of 0.5 and 1.0% for 24 h. Samples were taken at 24 h, and viable count of micoflora, gas, pH, volatile organic compounds and short-chain fatty acids were determined. The viable count of Enterobacteriaceae was significantly decreased (p<0.001) in all treatments added with prebiotics in comparison to control without prebiotics. However, the increase of lactic acid bacteria was observed in the prebiotics treatment. Gas production increased as the level of prebiotics increased. The pH values in the fermentation fluid decreased in a dose-dependent manner with increasing the concentration of prebiotics. The fermentation with prebiotics resulted in the reduction of malodorous compounds such as ammonia, hydrogen sulfide, indole and skatole. The increase in short-chain fatty acid (SCFA) production was observed in the treatments with prebiotics. In conclusion, the results of this study demonstrated that the fermentation with prebiotics was effective in reducing the formation of malodorous compounds and increasing lactic acid bacteria and SCFA. These effects depended on the concentration of prebiotics. Moreover, further study is needed to determine whether the in vitro efficacy on the reduction of malodorous compounds and increase of SCFA would also be observed in animals.

• Korean Journal of Microbiology
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• v.49 no.1
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• pp.24-29
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• 2013

In the present study, the effects of prebiotics and prebiotics+probiotics on intestinal microflora and fermentation products were evaluated in a pig in vitro fermentation model. The substrates used in this study were iso-malto oligosaccharide (IMO), partially digested chicory-inulin (CI), raffinose (RA), and cyclodextrin (CD) as prebiotics and Lactobacillus reiteri as probiotics. For a pig in vitro fermentation, the experimental diet for growing pigs was predigested using digestive enzymes secreted by small intestine and this hydrolyzed diet was mixed with a buffer solution containing 5% fresh swine feces. The mixture was then incubated with either prebiotics or prebiotics+probiotics for 24 h. Samples were taken at 24 h, and viable counts of microflora, gas, pH, volatile organic compounds (VOCs) and short-chain fatty acid (SCFA) were analyzed. The viable count of Enterobacteriaceae was significantly decreased (p<0.001) in all treatments containing prebiotics and prebiotics+probiotics when compared to the control. However, the number of lactic acid bacteria increased in the prebiotics and prebiotics+probiotics treatment. The pH values in the fermentation fluid decreased in all treatments when compared to the control, and their effects were greater in the prebiotics+probiotics group than prebiotics group. Fermentation with prebiotics resulted in a reduction in malodorous compounds such as ammonia, hydrogen sulfide and skatole when compared to the prebiotics+probiotics group. Short-chain fatty acid production was also higher for treatment with prebiotics+probiotics than treatment with prebiotics. In conclusion, the results of this study demonstrated that fermentation with prebiotics was effective in reducing the formation of malodorous compounds and prebiotics+probiotics was effective in increasing lactic acid bacteria and SCFA and reducing the pH. Moreover, further studies will be needed to determine whether the results observed in the in vitro model would occur in pigs that ingest these prebiotics or probiotics.