• Journal of Pharmaceutical Investigation
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• 제17권4호
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• pp.175-181
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• 1987

To increase the dissolution rate of furosemide, chitin and chitosan which are widely occurring biodegradable natural materials were used as drug carriers. The ground mixtures of furosemide with chitin or chitosan were prepared by grinding in a ball mill. The ground mixture showed a faster and more enhanced dissolution rate than the physical mixture or intact furosemide. The crystalline peaks of furosemide disappeared in the ground mixtures indicating the production of amorphous form. The comparison of infrared spectra of the physical mixture and the ground mixture showed an interaction such as association between the functional groups of furosemide and chitin or chitosan in the molecular level. The weight losses in TGA curves showed all the same patterns. However, the endothermic peak due to the fusion of furosemide in DTA curve disappeared in the ground mixture indicating the different thermal property. The dissolution of furosemide from ground mixtures was fast in the order of chitosan and then chitin. The co-grinding technique with chitin or chitosan provided a promising way enhancing the dissolution rate of practically insoluble drug.

• Archives of Pharmacal Research
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• 제26권2호
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• pp.173-181
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• 2003

A polymeric micelle drug delivery system was developed to enhance the solubility of poorly-water soluble drug, biphenyl dimethyl dicarboxylate, DDB. The block copolymers consisting of poly(D,L-lactide) (PLA) as the hydrophobic segment and methoxy poly(ethylene glycol) (mPEG) as the hydrophilic segment were synthesized and characterized by NMR, DSC and MALDI-TOF mass spectroscopy. The size of the polymeric micelles measured by dynamic light scattering showed a narrow monodisperse size distribution with the average diameter less than 50 nm. The MW of mPEG-PLA, 3000 (MW of mPEG, 2 K; MW of PLA, 1K), and the presence of hydrophilic and hydrophobic segments on the polymeric micelles were confirmed by MALDI-TOF mass spectroscopy and NMR, respectively. Polymeric micelle solutions of DDB were prepared by three different methods, i.e. the matrix method, emulsion method and dialysis method. In the matrix method, DDB solubility was reached to 13.29 mg/mL. The mPEG-PLA 2K-1K micelle system was compared with the poloxamer 407 micelle system for their critical micelle concentration, micelle size, solubilizing capacity, stability in dilution and physical state. DDB loaded-polymeric micelles prepared by the matrix method showed a significantly increased aqueous solubility (＞5000 fold over intrinsic solubility) and were found to be superior to the poloxamer 407 micelles as a drug carrier.

• Archives of Pharmacal Research
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• 제18권6호
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• pp.427-433
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• 1995

A microscopic mass balance approach has hsown that the initial saturation (Is), absorption number (An), dose number (Do), and dissolution number (Dn) are four fundamental dimensionless parameters that can be used to estimate the fraction dose absorbed (F)l of suspensions of poorly soluble drugs in humans. The dissolution number of a drug increases with decreasing its particle size. The effect of micronization on F for suspensions was investigated in terms of Dn. About 90% of maximal F can be achieved at $Dn{\approx}2$. Increasing the solubility of a drug results in better oral absorption through increasing Dn and decreasing the solubility of a drug results in better oral absorption through increasing Dn and decreasing Do. The fractions dose absorbed of digoxin, griseofulvin, and benoxaprofen agree with predicted F values sorbed by reducing particle size, while absorption of drugs with high Do and low Dn is limited by solubility and requires higher solubility to enhance the fraction dose absorbed in addition to micronization. Solubility at the physiological pH should be used for the estimation of the fraction dose absorbed.

• 대한화장품학회:학술대회논문집
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• 대한화장품학회 2003년도 IFSCC Conference Proceeding Book II
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• pp.319-329
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• 2003

Ursolic acid (UA) and oleanolic acid (OA) are pentacyclic triterpenoids which are widely distributed in plants, and their derivatives are aglycones of many naturally occurring saponins. It is known that pentacyclic acids may possibly enhance the mechanical barrier functions of cell membranes in plants. Recently, it has been reported that OA and UA have interesting biological activities on skin, such as anti-inflammatory and anti-wrinkle activities. Since triterpenoids are extremely insoluble and their solubility problem limits skin-care application, OA and UA were encapsulated in liposomes via micelle-to-vesicle transition to overcome poorly soluble property and enhance biological efficacy. Optimal molar ratio of OA to lecithin was found to exist for producing liposomes of small hydrodynamic size and liposomal suspensions without recrystallized precipitation of OA. From electron micrograph and dynamic light scattering studies, reconstituted OA-containing liposomes without severe mechanical treatment showed small hydrodynamic size about 150 nm. Wide-angle X-ray diffraction coupled with dynamic light scattering revealed that optimal amount of OA in liposome was 25.4 mole %. In biological evaluation, OA-containing liposome significantly increased filaggrin and transglutaminase as markers of keratinocyte differentiation in epidermal layer of hairless mouse, whereas ursolic acid-containing liposome did not show noticeable increase of filaggrin and transglutaminase compared to empty liposome. It is concluded that nano-scaled liposomes containing triterpenoids were spontaneously prepared by vesicular transition from mixed micelle and liposomal triterpenoids can enhance skin absorption of triterpenoid and biological efficacy.

• 약학회지
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• 제59권2호
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• pp.70-76
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• 2015

A Softgel is an oral dosage form for medicine similar to capsules and softgel dosage form offers several advantages over other oral dosage forms, such as delivering a liquid matrix designed to solubilize and improve the oral bioavailability of a poorly soluble compound as a unit dose solid dosage form, delivering low and ultra-low doses of a compound. This study aimed to qualify a proprietary vegetable soft capsule which contains modified starch and carrageenan as capsule shell components compare to the conventional gelatin softgel. Four kinds of samples were prepared with vegetable and gelatin capsule shell, respectively. Morphology of capsule shell, mechanical strength of capsule, and hygroscopic properties were studied for comparing the quality attributes of softgel. Short-term stability against heat and moisture was also investigated in this study. Vegetable capsule shell showed better mechanical strength, physical stability and disintegration time for temperature and humidity than those of conventional gelatin capsule shell with four different filling materials used frequently as soft capsule form. Conclusively, this vegetable capsule shell polymer system can replace easily gelatin-shell systems and additionally allows encapsulation of lipid fills at high temperatures that are semisolid or solid-like at room temperature.

• Parasites, Hosts and Diseases
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• 제57권2호
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• pp.201-206
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• 2019

The roles of mast cells in allergic diseases and helminth infections are well known. However, the roles of mast cells in T. gondii infection is poorly understood. This study was focused on the production of pro-inflammatory cytokines ($TNF-{\alpha}$, IL-4), chemokines (CXCL8, MCP-1) and nitric oxide (NO) by mast cells in response to soluble lysate of T. gondii tachyzoites. Production of CXCL8 (IL-8), MCP-1, $TNF-{\alpha}$ and IL-4 were measured by RT-PCR and ELISA. Western blot were used for detection of CXCR-1 and CXCR2. Our results showed that T. gondii lysates triggered mast cells to release CXCL8, MCP-1, $TNF-{\alpha}$, IL-4 and to produce NO. This suggests that mast cells play an important role in inflammatory responses to T. gondii.

• 한국분말재료학회지
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• 제30권4호
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• pp.305-309
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• 2023

This study aims to prepare a colloidal silica-containing powder to enhance the solubility and dissolution rate of rivaroxaban using a self-nanoemulsifying drug delivery system (SNEDDS). We investigate the impact of colloidal silica on a nanoemulsion system for preparing powdered SNEDDS. The liquid SNEDDS comprises 30/20/50 (w/w/w) Peceol/Cremophor RH40/Tween 80, which results in the formation of the smallest droplets. Three powdered SNEDDS formulations are prepared by suspending the liquid SNEDDS formulation using colloidal silica and spray drying. The powdered SNEDDS prepared with liquid SNEDDS and colloidal silica at a ratio of 1/0.5 (w/w) exhibits the highest water solubility (0.94 ± 0.62 vs. 26.70 ± 1.81 ㎍/mL) and dissolution rate (38.4 ± 3.6 vs. 85.5 ± 3.4%, 45 min) when compared to the drug alone. Morphologically, the liquid SNEDDS is adsorbed onto colloidal silica and forms smaller particles. In conclusion, an SNEDDS containing rivaroxaban, prepared using colloidal silica, facilitates the creation of a nanoemulsion and enhances the water solubility of rivaroxaban. Accordingly, this technology holds significant potential for commercialization.

• 한국분말재료학회지
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• 제31권3호
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• pp.263-271
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• 2024

This study focused on improving the solubility of silodosin, a drug poorly soluble in water, by utilizing solid dispersions. Three types of dispersions were examined and compared against the drug powder: surface-attached (SA), solvent-wetted (SW), and solvent-evaporated (SE). Polyvinyl alcohol (PVA) was identified as the most effective polymer in enhancing solubility. These dispersions were prepared using spray-drying techniques with silodosin and PVA as the polymer, employing solvents such as water, ethanol, and a water-acetone mix. The physicochemical properties and solubility of the dispersions were evaluated. The surface-attached dispersions featured the polymer on a crystalline drug surface, the solvent-wetted dispersions had the amorphous drug on the polymer, and the solvent-evaporated dispersions produced nearly round particles with both components amorphous. Testing revealed that the order of improved solubility was: solvent-evaporated, solvent-wetted, and surface-attached. The results demonstrated that the preparation method of the solid dispersions significantly impacted their physicochemical properties and solubility enhancement.

• 한국대기환경학회지
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• 제31권1호
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• pp.28-40
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• 2015

To investigate the seasonal variations of carbonaceous aerosol in Daejeon, OC (organic carbon), EC (elemental carbon) and WSOC (water soluble organic carbon) in $PM_{2.5}$ samples collected from March 2012 to February 2013 were analyzed. $PM_{2.5}$ concentrations were estimated by the sum of organic matter ($1.6{\times}OC$), EC, water-soluble ions ($Na^+$, $NH_4{^{+}}$, $K^+$, $Mg^{2+}$, $Ca^{2+}$, $Cl^-$, $SO_4{^{2-}}$, $NO_3{^{-}}$). The estimated $PM_{2.5}$ concentrations were relatively higher in winter ($29.50{\pm}12.04{\mu}g/m^3$) than those in summer ($13.72{\pm}6.92{\mu}g/m^3$). Carbonaceous aerosol ($1.6{\times}OC+EC$) was a significant portion (34~47%) of $PM_{2.5}$ in all season. The seasonally averaged OC and WSOC concentrations were relatively higher in winter ($6.57{\times}3.48{\mu}gC/m^3$ and $4.07{\pm}2.53{\mu}gC/m^3$ respectively), than those in summer ($3.07{\pm}0.8{\mu}gC/m^3$, $1.77{\pm}0.68{\mu}gC/m^3$, respectively). OC was correlated well with WSOC in all season, indicating that they have similar emission sources or formation processes. In summer, both OC and WSOC were weakly correlated with EC and also poorly correlated with a well-known biomass burning tracer, levoglucosan, while WSOC is highly correlated with SOC (secondary organic carbon) and $O_3$. The results suggest that carbonaceous aerosol in summer was highly influenced by secondary formation rather than primary emissions. In contrast, both OC and WSOC in winter were strongly correlated with EC and levoglucosan, indicating that carbonaceous aerosol in winter was closely related to primary source such as biomass burning. The contribution of biomass burning to $PM_{2.5}$ OC and EC, which was estimated using the levoglucosan to OC and EC ratios of potential biomass burning sources, was about $70{\pm}15%$ and $31{\pm}10%$, respectively, in winter. Results from this study clearly show that $PM_{2.5}$ OC has seasonally different chemical characteristics and origins.

• Asian-Australasian Journal of Animal Sciences
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• 제22권3호
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• pp.356-364
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• 2009

The current ruminant feeding models require parameterization of the digestion kinetics of carbohydrate fractions in feed ingredients to estimate the supply of nutrients from a ration. Using an automated gas production technique, statistically welldefined digestion rate of carbohydrate, including soluble carbohydrate, can be estimated in a relatively easy way. In this study, the gas production during in vitro fermentation was measured and recorded by an automated gas production system to investigate degradation kinetics of carbohydrate fractions of a wide range of ruminant feeds: corn silage, rice straw, corn, soybean hull, soybean meal, and cell mass from lysine production (CMLP). The gas production from un-fractionated, ethanol insoluble residue and neutral detergent insoluble residue of the feed samples were obtained. The gas profiles of carbohydrate fractions on the basis of the carbohydrate scheme of the Cornell Net Carbohydrate and Protein System (A, B1, B2, B3 and C) were generated using a subtraction approach. After the gas profiles were plotted with time, a curve was fitted with a single-pool exponential equation with a discrete lag to obtain kinetic parameters that can be used as inputs for modern nutritional models. The fractional degradation rate constants (Kd) of corn silage were 11.6, 25.7, 14.8 and 0.8%/h for un-fractioned, A, B1 and B2 fractions, respectively. The values were statistically well estimated, assessed by high t-value (>12.9). The Kd of carbohydrate fractions in rice straw were 4.8, 21.1, 5.7 and 0.5%/h for un-fractioned, A, B1 and B2 fractions, respectively. Although the Kd of B2 fraction was poorly defined with a t-value of 4.4, the Kd of the other fractions showed tvalues higher than 21.9. The un-fractioned corn showed the highest Kd (18.2%/h) among the feeds tested, and the Kd of A plus B1 fraction was 18.7%/h. Soybean hull had a Kd of 6.0, 29.0, 3.8 and 13.8%/h for un-fractioned, A, B1 and B2, respectively. The large Kd of fraction B2 indicated that NDF in soybean hull was easily degradable. The t-values were higher than 20 except for the B1 fraction (5.7). The estimated Kd of soybean meal was 9.6, 24.3, 5.0%/h for un-fractioned, A and B1 fractions, respectively. A small amount of gas (5.6 ml at 48 ho of incubation) was produced from fermentation of CMLP which contained little carbohydrate. In summary, the automated gas production system was satisfactory for the estimation of well defined (t-value >12) kinetic parameters and Kd of soluble carbohydrate fractions of various feedstuffs that supply mainly carbohydrate. The subtraction approach, however, should be applied with caution for some concentrates, especially those which contain a high level of crude protein since nitrogen-containing compounds can interfere with gas production.