• Proceedings of the PSK Conference
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• 2001.04a
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• pp.233.2-234
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• 2001

• Journal of Pharmaceutical Investigation
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• v.38 no.4
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• pp.241-247
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• 2008

Paclitaxel is a taxane diterpene amide, which was first extracted from the stem bark of the western yew, Taxus brevifolia. This natural product has proven to be useful in the treatment of a variety of human neoplastic disorders, including ovarian cancer, breast and lung cancer. Paclitaxel is a highly hydrophobic drug that is poorly soluble in water. It is mainly given by intravenous administration. Therefore, The pharmaceutical formulation of paclitaxel ($Taxol^{(R)}$; Bristol-Myers Squibb) contains 50% $Cremophor^{(R)}$ EL and 50% dehydrated ethanol. However the ethanol/Cremophor EL vehicle required to solubilize paclitaxel in $Taxol^{(R)}$ has a pharmacological and pharmaceutical problems. To overcome these problems, new formulations for paclitaxel that do not require solubilization by $Cremophor^{(R)}$ EL are currently being developed. Therefore this study utilized a supercritical fluid antisolvent (SAS) process for cremophor-free formulation. To select hydrophilic polymers that require solubilization for paclitaxel, we evaluated polymers and the ratio of paclitaxel/polymers. HP-${\beta}$-CD was used as a hydrophilic polymer in the preparation of the paclitaxel solid dispersion. Although solubility of paclitaxel by polymers was increased, physical stability of solution after paclitaxel/polymer powder soluble in saline was unstable. To overcome this problem, we investigated the use of surfactants. At 1/20/40 of paclitaxel/hydrophilic polymer/ surfactant weight ratio, about 10 mg/mL of paclitaxel can be solubilized in this system. Compared with the solubility of paclitaxel in water ($1\;{\mu}g/mL$), the paclitaxel solid dispersion prepared by SAS process increased the solubility of paclitaxel by near 10,000 folds. The physicochemical properties was also evaluated. The particle size distribution, melting point and amophorization and shape of the powder particles were fully characterized by particle size distribution analyzer, DSC, SEM and XRD. In summary, through the SAS process, uniform nano-scale paclitaxel solid dispersion powders were obtained with excellent results compared with $Taxol^{(R)}$ for the physicochemical properties, solubility and pharmacokinetic behavior.

• Clean Technology
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• v.15 no.4
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• pp.233-238
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• 2009

Supercritical fluid processes have gained great attention as a new and environmentally-benign method of preparing the microparticles of energetic materials like explosives and propellants. In this work, RDX (cyclotrimethylenetrinitramine) was selected as a target explosive. The microparticle formation of RDX using supercritical anti-solvent (SAS) recrystallization process was performed and the effect of operating variables on the size and morphology of prepared particles was observed. N,N-Dimethylformamide was used as organic solvent for dissolving the RDX. The size of the RDX particles decreased remarkably up to less than $10\;{\mu}m$ by SAS recrystallization. In the range of operating conditions of the SAS process studied in this work, the finest RDX particles were obtained at 313.15K, 150 bar, and 15wt% RDX concentration in feed solution.

• Polymer(Korea)
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• v.31 no.2
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• pp.168-176
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• 2007

The sub-micron particles of poly ($\gamma-glutamic$ acid) (PGA) containing lysozyme have been prepared using supercritical antisolvent (SAS) precipitation process at various experimental conditions such as pressure, temperature, inner diameter of nozzle, and concentration. As overall results of the application of SAS process to this system, the smaller size powder has been produced as (i) increasing pressure, (ii) decreasing temperature, (iii) decreasing the inner diameter of nozzle, and (iv) decreasing the concentration of PGA and lysozyme. It is found by means of FT-IR analysis that during SAS process, the composition has changed from the original composition of PGA : lysozyme=50 : 50 into PGA : lysozyme=33 : 67 at final product powder. It means that PGA has higher solubility for the mixed solvent of carbon dioxide and dimethyl sulfoxide (DMSO). Due to such difference of solubility, this particle forms the core-shell structure of which the core consists mainly of lysozyme. It is also found that the residual DMSO amount of $7.8\times10^{-3}wt%$ exists inside the powder.

• Korean Chemical Engineering Research
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• v.46 no.5
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• pp.958-964
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• 2008

In this work, micro-sized dextran particles, which have recently been focused as one of the candidate materials for the Drug Delivery System(DDS), were prepared by means of the Supercritical Antisolvent (SAS) process with $CO_2$. With dimethyl sulfoxide(DMSO) as the solvent, effects of the operating variables such as temperature (308.15~323.15 K), pressure(90~130 bar), solute concentration(10~20 mg/ml), and the molecular weight of the solute(Mw=37,500, 450,000) on the size and morphology of the resulting particles were thoroughly observed. The higher solute concentration led to the larger particles, however, the injection velocity of the solution and pressure did not show significant effects on the resulting particle size. With dextran of the lower molecular weight, the smallest particles were obtained at 313.15 K. On the other hand, the size of the particles from the high molecular weight dextran ranged between $0.1{\sim}0.5{\mu}m$ with an incremental effect of the temperature and pressure. For the solute concentration of 5 mg/ml, the lower molecular weight dextran did not form discrete particles while aggregation of the particles appeared when the solute concentration exceeded 15 mg/ml for the higher molecular weight dextran. It is believed that if the solute concentration is too low, the degree of the supersaturation in the recrystallization chamber would not be sufficient for initiation of the nucleation and growth mechanism. Instead, the spinodal decomposition mechanism leads to formation of the island-like phase separation which appears similar to aggregation of the discrete particles. This effect would be more pronounced for the smaller molecular weight polymer system due to the narrower phase-splitting region.

• Clean Technology
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• v.13 no.1 s.36
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• pp.28-33
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• 2007

We measured cloud points of Poly(methylmethacrylate) (PMMA) in various solvents using the high-pressure variable volume view cell apparatus. The solvents used for dissolving PMMA were chlorodifluoromethane (HCFC-22), dimethylether (DME), 1,1,1-trifluoroethane (HFC-143a), 1,1-difluoroethane (HFC-152a) and 1,1,1,2-tetrafluoroethane (HFC-134a), and the effect of $CO_2$ concentration on the phase behavior of $PMMA+HCFC-22+CO_2$ system and $PMMA+DME+CO_2$ system was observed. PMMA was dissolved well in HCFC-22 from about 340 K, 5MPa and in DME from about 300 K, 28MPa. However, PMMA was not dissolved at all up to 423.15 K, 160MPa in the other fluorine compound such as HFC-l43a, HFC-152a and HFC-134a. PMMA+HCFC-22, $PMMA+HCFC-22+CO_2$ and PMMA+DME systems exhibit the lower critical solution temperature (LCST) behavior, however, $PMMA+DME+CO_2$ system exhibits the upper critical solution temperature (UCST) behavior. In the $CO_2$ mixture, the cloud point pressure of PMMA was increased dramatically proportional to the amount of $CO_2$ added, and from this result, it was known that $CO_2$ could be used as an antisolvent for fabricating PMMA nano-particles. And the cloud point of PMMA could be controlled by changing the concentration of $CO_2$.