• Proceedings of the Korean Vacuum Society Conference
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• 2016.02a
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• pp.142.1-142.1
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• 2016

We present bulk diffusion rates of hydroxide ions in amorphous solid water (ASW) at 135 ~ 160 K. Previous researches showed that the diffusion mechanism of hydroxide is different from one of hydronium ions, and this implies that they have different diffusion rates. In ultra-high vacuum (UHV) chamber, low-energy scattering (LES) was used to measure ion population and temperature-programmed desorption (TPD) was conducted for measuring ASW thicknesses. To determine the diffusion rates, a simple model for $H_2O/NaOH/H_2O$ sandwich films was developed using Fick's second law. The measured surface population of hydroxide ions as a function of time was well fitted to the model, and the rates were well agreed to an Arrhenius equation.

• KSBB Journal
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• v.26 no.4
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• pp.283-292
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• 2011

Solid dispersion is one of well-established pharmaceutical techniques to improve the dissolution and consequent bioavailability of poorly water soluble drugs. It is defined as a dispersion of drug in an inert carrier matrix. Solid dispersions can be classified into three generations according to the carrier used in the system. First and second generations consist of crystalline and amorphous substances, respectively. Third generation carriers are surfactant, mixture of polymer and surfactants, and mixture of polymers. Solid dispersions can be generallyprepared by melting method and solvent method. While melting method requires high temperature to melt carrier and dissolve drug, solvent method utilizes solvent to dissolve the components. The improvement in dissolution through solid dispersions is attributed to reduction in drug particle size, improvement in wettability, and/or formation of amorphous state. The primary characteristics of solid dispersions, the presenceof drug in amorphous state, could be determined by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and fourier-transformed infrared spectroscopy (FTIR). In spite of the significant improvement in dissolution by solid dispersion technique, some drawbacks have limited the commercial application of solid dispersions. Thus, further studies should be conducted in a direction to improve the congeniality to commercialization.

• Archives of Pharmacal Research
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• v.28 no.7
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• pp.866-874
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• 2005

The objective of this study was to elucidate the feasibility to improve the solubility and bioavailability of poorly water-soluble itraconazole via solid dispersions by using supercritical fluid (SCF). Solid dispersions of itraconazole with hydrophilic polymer, HPMC 2910, were prepared by the aerosol solvent extraction system (ASES) under different process conditions of temperature/pressure. The particle size of solid dispersions ranged from 100 to 500 nm. The equilibrium solubility increased with decrease (15 to 10 MPa) in pressure and increase (40 to $60^{\circ}C$) in temperature. The solid dispersions prepared at $60^{\circ}C$/15 MPa showed a slight increase in equilibrium solubility (approximately 27-fold increase) when compared to pure itraconazole, while those prepared at $60^{\circ}C$/10MPa showed approximately 610-fold increase and no endothermic peaks corresponding to pure itraconazole were observed, indicating that itraconazole might be molecularly dispersed in HPMC 2910 in the amorphous form. The amorphous state of itraconazole was confirmed by DSC/XRD data. The pharmacokinetic parameters of the ASES-processed solid dispersions, such as $T_{max},\;C_{max},\;and\;AUC_{0-24h}$ were almost similar to $Sporanox_{\circledR}$ capsule which shows high bioavailability. Hence, it was concluded that the ASES process could be a promising technique to reduce particle size and/or prepare amorphous solid dispersion of drugs in order to improve the solubility and bioavailability of poorly water-soluble drugs.

• Journal of Pharmaceutical Investigation
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• v.32 no.2
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• pp.73-80
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• 2002

Cefuroxime axetil is a cephalosporin antibiotic having a high activity against a wide spectrum of Grampositive and Gram-negative microorganisms. It is a cephalosporin antibiotic which exist as 2 diastereoisomers: diastereoisomer A and B. It shows polymorphism of three forms: a crystalline form having a melting point of about $180^{\circ}C$, a substantially amorphous form having a high melting point of about $135^{\circ}C$ and a substantially amorphous form having a low melting point of about 70^{\circ}C$. The crystalline form of cefuroxime axetil is slightly soluble in water because diastereoisomer A has lower solubility than B in water. Substantially amorphous form of which there are no difference in solubility between diastereoisomer A and B has better solubility than crystalline form, but it forms a thicker gel than crystalline form upon contact with an aqueous medium. Based on this reason, cefuroxime axetil is not readily absorbable in the gastrointestinal tract, rendering its bioavailability on oral administration very low. The object of this study was to develop an improved non-crystalline cefuroxime axetil composition having a high physicochemical stability and bioavailability. A non-crystalline cefuroxime axetil solid dispersant showing no peak on a Differential Scanning Calorimetry (DSC) scan is prepared by dissolving cefuroxime axetil and a surfactant in an organic solvent; suspending a water-insoluble inorganic carrier in the resulting solution; and spray drying the resulting suspension to remove the organic solvent, said solid dispersant having an enhanced dissolution and stability of cefuroxime axetil and being useful for the preparation of a pharmaceutical composition for oral administration. Tablet was formulated with this cefuroxime axetil solid dispersant, disintegrants and other ingredients. It disintegrated and dissolved easily and dynamically in dissolution medium, so showed a good dissolution profile.

• Journal of Pharmaceutical Investigation
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• v.34 no.6
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• pp.443-452
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• 2004

Habit is the description of the outer appearance of a crystal. If the environment of a growing crystal affects its external shape without changing its internal structure, a different habit results. Crystal habit and the internal structure of a drug can affect bulk and physicochemical properties, which range from flowability to chemical stability. A polymorph is a solid crystalline phase of a given compound resulting from the possibility of at least two different arrangements of the molecules of that compound in the solid state. Chemical stability and solubility changes due to polymorphism can have an impact on a drug's bioavailability and its development program. During crystallization from a solution, crystals separating may consist of a pure component or be a molecular compound. Solvates are molecular complexes that have incorporated the crystallizing solvent molecule in their lattice. When the solvent incorporated in the solvate is water, it is called a hydrate. To distinguish solvates from polymorphs, which are not molecular compounds, the term pseudopolymorph is used. Identification of possible hydrate compounds is important since their aqueous solubilities can be significantly less than their anhydrous forms. Conversion of an anhydrous compound to a hydrate within the dosage form may reduce the dissolution rate and extent of drug absorption. An amorphous solid may be treated as a supercooled liquid in which the arrangement of molecules is random. Amorphous solids lack the three-dimensional long-range order found in crystalline solids. Since amorphous forms are usually of higher thermodynamic energy than corresponding crystalline forms, solubilities as well as dissolution rates are generally greater. A study on crystal form includes characterization of (l)crystal habit, (2)polymorphism, (3)pseudopolymorphism, (4)amorphous solid.

• Journal of Pharmaceutical Investigation
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• v.32 no.3
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• pp.173-179
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• 2002

Solid dispersions of ipriflavone with PVP were prepared by a spray-drying method in order to improve the bioavailability. They were measured with scanning electron microscopy, differential scanning calorimetry, x-ray powder diffraction, and Fourier transform infrared spectroscopy to evaluate the physicochemical interaction between ipriflavone and PVP and study the correlation between these physicochemical characteristics and bioavailability. Ipriflavone exhibited crystallinity, whereas PVP was almost amorphous. The area of the endotherm $({\Delta}H)$ of freezer milled ipriflavone, freezer milled ipriflavone physically mixed with freezer milled PVP, and physically mixed ipriflavone with PVP was almost the same, whereas ${\Delta}H$ of the solid dispersed ipriflavone with PVP was much smaller than that of the other preparation types. Also, the crystallinity and the crystal size of ipriflavone in the solid dispersed ipriflavone with PVP were much smaller than those of the other preparation types. From the in vivo test, the AUC of the solid dispersed ipriflavone with PVP was approximately 10 times higher than that of the physically mixed ipriflavone with PVP. The solid dispersion using the spray-drying method with a water-soluble polymer, PVP, may be effective for the improvement of the bioavailability.

• Proceedings of the Korean Institute of Electrical and Electronic Material Engineers Conference
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• 2002.07b
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• pp.670-673
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• 2002

Powder synthesis using the alkoxy precursor technique exhibits processing flexibility not available in traditional high temperature solid-state reaction. With proper process control, impurities can be reduced to very low levels. The major distinction of the present work lies in the method of accomplishing the hydrolysis reaction. In the present case, water is not added to the system. Instead the metal alkoxide/alcohol solution is heated to a temperature at which water is formed through dehydration of the alcohol solvent, causing precipitation of the corresponding metal oxide (hydroxide). The present method provides a means of producing amorphous alumina.

• 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.

• Korean Journal of Mineralogy and Petrology
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• v.34 no.1
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• pp.31-40
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• 2021

The hydrogen in nominally anhydrous mineral is known to be associated with lattice defects, but it also can exist in the form of water and hydroxyl groups on the large surface of the nanoscale particles. In this study, we investigate the effectiveness of 1H solid-state nuclear magnetic resonance (NMR) spectroscopy as a robust experimental method to quantify the hydrogen atomic environments of amorphous silica nanoparticles with varying relative humidity. Amorphous silica nanoparticles were packed into NMR rotors in a temperature-humidity controlled glove box, then stored in different atmospheric conditions with 25% and 70% relative humidity for 2~10 days until 1H NMR experiments, and a slight difference was observed in 1H NMR spectra. These results indicate that amount of hydrous species in the sample packed in the NMR rotor is rarely changed by the external atmosphere. The amount of hydrogen atom, especially the amount of physisorbed water may vary in the range of ~10% due to the temporal and spatial inhomogeneity of relative humidity in the glove box. The quantitative analysis of 1H NMR spectra shows that the amount of hydrogen atom in amorphous silica nanoparticles linearly increases as the relative humidity increases. These results imply that the sample sealing capability of the NMR rotor is sufficient to preserve the hydrous environments of samples, and is suitable for the quantitative measurement of water content of ultrafine nominally anhydrous minerals depending on the atmospheric relative humidity. We expect that 1H solid-state NMR method is suitable to investigate systematically the effect of surface area and crystallinity on the water content of diverse nano-sized nominally anhydrous minerals with varying relative humidity.

• Journal of Pharmaceutical Investigation
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• v.40 no.3
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• pp.181-185
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• 2010

The objective of this study was to improve the extent of drug release as well as the dissolution rate of TD49, a novel algicidal agent, via the preparation of solid dispersion (SD). Among the various carriers tested, $Solutol^{(R)}$ HS15 was most effective to enhance the solubility of TD49. Subsequently, SDs of TD49 were prepared by using $Solutol^{(R)}$ HS15 and their solubility, dissolution characteristics and drug crystallinity were examined at various drug-carrier ratios. Solubili ty of TD49 was increased significantly in accordance with increasing the ratio of $Solutol^{(R)}$ HS15 in SDs. Compared to untreated powders and physical mixtures (PMs), SDs facilitated the faster and greater extent of drug release in water. Particularly, SD having the drug-carrier ratio of 1:20 exhibited approximately 90% of drug release within 1 hr. Differential scanning calorimetry (DSC) thermograms and X-ray diffraction (XRD) patterns suggested that SDs might enhance the dissolution of TD49 by changing the drug crystallinity to an amorphous form in addition to the increased solubilization of drug in the presence of $Solutol^{(R)}$ HS15. In conclusion, SD using $Solutol^{(R)}$ HS15 appeared to be effective to improve the extent of drug release and the dissolution rate of poorly water soluble TD49.