• Journal of Pharmaceutical Investigation
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• v.41 no.4
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• pp.239-247
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• 2011

Simvastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate, an early and rate-limiting step in the biosynthesis of cholesterol. Simvastatin has good permeability, but it also has low solubility (BCS class II), which reduces its bioavailability. To overcome this problem, a solid dispersion is formed using a spray-dryer with polymeric material carrier to potentially enhance the dissolution rate and extend drug absorption. As carriers for solid dispersion, Gelucire$^{(R)}$44/14 and Gelucire$^{(R)}$ 50/13 are semisolid excipients that greatly improve the bioavailability of poorly-soluble drugs. To avoid any toxic effects of an organic solvent, we used aqueous medium to melt Tween$^{(R)}$ 80 and distilled water. The structural behaviors of the raw materials and the solid dispersion were analyzed by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). The DSC and PXRD data indicated that the crystalline structure of simvastatin was transformed to an amorphous structure through solid dispersion. Then, solid dispersion-based tablets containing 20 mg simvastatin were prepared with excipients. Dissolution tests were performed in distilled water and artificial intestinal fluid using the USP paddle II method. Compared with that of the commercial tablet (Zocor$^{(R)}$ 20 mg), the release of simvastatin from solid dispersion based-tablet was more efficient. Although the stability study is not complete, this solid dispersion system is expected to deliver poorly water-soluble drugs with enhanced bioavailability and less toxicity.

• YAKHAK HOEJI
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• v.28 no.3
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• pp.161-167
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• 1984

To improve the solubility properties of indomethacin, a poorly water-soluble drug, some attempts were made with surfactants, such as sodium deoxycholate, sodium laurylsulfate and polysorbate-80. The enhancement effect in solubility was found to be due to the micellar solubilization and dependent on the concentration of surfactants, pH and temperature. The mechanism of interaction was suggested to be attributed to the formation of mixed micelles between the drug and solubilizers.

• Clean Technology
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• v.16 no.2
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• pp.80-87
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• 2010

In this study, micro- and submicron particles of itraconazole, a poorly water-soluble antifungal drug, were prepared for improving its aqueous solubility using an ultrasound-assisted supercritical fluid technique, called SAS-EM. The SAS-EM process used in our experiments was different from the conventional SAS-EM in that the ultrasound was applied directly to the spray nozzle. The effect of the ultrasonic power, temperature, and solvent on the formation of itraconazole particles were investigated. Smaller particles were obtained through our SAS-EM process compared with the ASES process, and the mean particle size decreased as the ultrasonic power increased. Our experimental results confirmed that the ultrasound-assisted supercritical fluid process is an efficient method for producing ultrafine particles.

• Journal of Pharmaceutical Investigation
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• v.20 no.1
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• pp.13-18
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• 1990

Hydrocortisone (HC) sustained-release suppositories were prepared by using a solid matrix of methacrylic acid-methacrylic acid methyl ester copolymer $(Eudragit\;L_{100}^{R}:\;EL)$ as a poorly water soluble carrier and polyethylene glycole 1540 (PEG) as an water soluble carrier. HC release rate was controlled by complexation with ${\beta}-cyclodextrin$ $({\beta}-CyD)$ which was confirmed by X-ray diffractometry, IR-spectroscopy and differential scanning calorimetry. Release rate of HC from the EL-PEG matrix suppositories decreased with increase of EL contents. The release rale from $HC-{\beta}-CyD$ complex decreased in the following order: $HC-{\beta}-CyD/PEG$ > HC/PEG > $HC-{\beta}-CyD/EL_{10%}-PEG$ > $HC/EL_{10%}-PEG$ > $HC-{\beta}-CyD/EL_{15%}-PEG$ > $HC/EL_{15%}-PEG$ > $HC-{\beta}-CyD/EL_{20%}-PEG$ > $HC/EL_{20%}-PEG$. The crystallinity of HC in polymer matrix was identified using X-ray diffractometer and the surface of matrix suppositories after release test was examined by scanning electron microscopy. The sustained release of HC from these matrix suppositories was attributed to the network structure of EL.

• Journal of Pharmaceutical Investigation
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• v.38 no.2
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• pp.111-117
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• 2008

To overcome the solubility of poorly water-soluble drug, the formation of solid dispersion using a spray-dryer with polymeric material, that can potentially enhance the dissolution rate extend of drug absorption was considered in this study. $Eudragit^{(R)}$ E100 as carrier for solid dispersion is acrylate copolymer that soluble in acidic buffer solutions (below pH 5.0). It was used to increase dissolution of atorvastatin calcium as a water-insoluble drug in acidic environments. In this study, a spray-dryer was used to prepare solid dispersion of atorvastatin calcium and $Eudragit^{(R)}$ E100 for purpose of improving the solubility of drug. Atorvastatin calcium and $Eudragit^{(R)}$ E100 were dissolved in ethanol and spray-dryed. DSC and XRD were used to analyze the crystallinity of the sample. It was found that atorvastatin calcium is amorphous in the $Eudragit^{(R)}$ E100 solid dispersion. FT-IR was used to analyze the salt formation by interaction between atorvastatin calcium and $Eudragit^{(R)}$ E100. Comparative dissolution study exhibited better dissolution characteristics than the commercial drug ($Lipitor^{(R)}$) as control. The dissolution rate of atorvastatin calcium was markedly increased in solid dispersion system in simulated gastric juice (pH 1.2). This study proposed that this solid dispersion system improved the bioavailability of poorly water-soluble atorvastatin calcium.

• Journal of Pharmaceutical Investigation
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• v.40 no.6
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• pp.339-345
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• 2010

Fenofibrate has been used for many years to lower cholesterol levels and its pharmacokinetic profile is well understood. However, due to its low solubility in water, it has low bioavailability after oral administration. In order to improve the dissolution rate, fenofibrate was formulated into a self-microemulsifying drug delivery systems (SMEDDS). We used pseudo-ternary phase diagrams to evaluate the area of microemulsification, and an in vitro dissolution test was used to investigate the dissolution rate of fenofibrate. The optimized formulation for in vitro dissolution assessment consisted of Lauroglycol FCC (60%), Solutol HS 15 (27%), and Transcutol-P (13%). The mean droplet size of the oil phase in the microemulsion formed from the SMEDDS was about 130 nm. The dissolution rate of fenofibrate from SMEDDS was significantly higher than that of the reference tablet. Our studies suggested that the fenofibrate containing SMEDDS composition can effectively increase the solubility and oral bioavailability of poorly water-soluble drugs.

• Korean Journal of Food Science and Technology
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• v.40 no.3
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• pp.360-363
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• 2008

Two barley malt samples were selected at two different stages of germination, a well-modified malt germinated for 96 hr and a poorly-modified malt for 60 hr, and were analyzed for total, insoluble, and soluble ${\beta}$-glucan contents. The total ${\beta}$-glucan content in raw barley was 3.96%, and the content was reduced during malting. The total ${\beta}$-glucan contents of the poorly- and well-modified malts were 1.02% and 0.18%, respectively. After 4 days of germination, approximately 95% of the ${\beta}$-glucan present in the barley was degraded. A significantly higher proportion of water-soluble ${\beta}$-glucan was found in the well-modified malt, suggesting that ${\beta}$-glucan solubility was dependent on cell wall modifications in the malt (${\beta}$-glucan breakdown). The proportion of water-soluble ${\beta}$-glucan was also affected by the extraction temperature. The two differently modified malts were mashed isothermally at 45, 55, 65, and 75oC for 2 hr. An increasing mashing temperature resulted in increased viscosity for the wort and the resulting beer. The viscosity of the wort from the well-modified malt was significantly low, due to its low initial malt ${\beta}$-glucan with increased solubility as well as a presumably sufficient ${\beta}$-glucanase activity during mashing.

• Journal of Pharmaceutical Investigation
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• v.27 no.3
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• pp.219-223
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• 1997

Terfenadine, antihistaminic drug, is poorly soluble in water. The purpose of this study is to investigate the possibility of using $terfenadine-{\beta}-cyclodextrin$ inclusion compound, instead of terfenadine, as the active substance of solid dosage form by improving the solubility, dissolution and anti-histaminic activity of terfenadine. The solubility and binding characteristics of $terfenadine-{\beta}-cyclodextrin$ complex in pH $1.2{\sim}6.8$ were investigated. Furthermore, the preparing method of $terfenadine-{\beta}-\;cyclodextrin$ inclusion compound was setting up and its physico-chemical characteristics such as DSC curve, solubility, dissolution and anti-histaminic activity were investigated. In conclusion, the solubility of terfenadine was increasing ${\beta}-cyclodextrin$ and with the decreasing pH. $Terfenadine-{\beta}-cyclodextrin$ inclusion compound, whose yield is almost 100%, was prepared by neutralization method. This inclusion compound was 200-times as soluble as terfenadine in pH 1.2-6.8. In addition, it had the faster dissolution and anti-histaminic activity than terfenadine. Therefore, it is used to the active substance of solid dosage form such as tablet and capsule in stead of terfenadine.

• The Journal of the Convergence on Culture Technology
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• v.7 no.4
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• pp.683-691
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• 2021

The purpose of this study is to measure the yield and to evaluate the physiological activity of Cannabis sativa seed(Hemp seed) extracts extracted using a density fluctuation supercritical carbon dioxide for each temperature condition-30℃(HSSE30), 45℃(HSSE45), 60℃(HSSE60), and to enable dissolution of the poorly water-soluble extracts by liposome formulation and to enhance the skin permeability. As a result of the yield measurement, HSSE60 showed the highest yield, and in the antioxidant activities, HSSE45 had the highest total polyphenol content, and showed the highest DPPH, ABTS+ radical scavenging activities at the highest concentration of the extracts. As a result of the antimicrobial susceptibility testing, a clear zone appeared only in the Propionibateium acnes strain. It was confirmed that particle size was reduced and the absolute value of the zeta potential increased in the case of the formulation in which the extracts were in liposomes than in the formulation in which the extracts were dissolved in deionized water, and the skin permeability was improved. Based on these experimental results, we confirmed the possibility of using the hemp seed supercritical carbon dioxide extracts, a poorly water-soluble extract, can be applied as a functional natural material for cosmetics.

• Journal of Powder Materials
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• v.30 no.4
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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.