• 한국자동차공학회논문집
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• 제9권6호
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• pp.16-23
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• 2001

Spray dispersion in high pressure diesel engines have been simulated experimentally with a special emphasis on the effect of swirl by using a liquid injection technique. A constant volume chamber was designed to be rotatable in order to generate a continuous swirl and to have the flow field closely resembling a solid body rotation. Emulsified fuel was injected into the chamber and the developing process of fuel sprays was visualized. The effect of swirl on the spray dispersion was quantified by calculating non-dimensionalized dispersion area according to the spray tip penetration length. The results show that the effect of swirl on the spray dispersion is different between short and long spray penetrations. For short range of spray tip penetration, the effect of swirl on spray dispersion is quite small. However, as the spray tip is penetrated into longer distance in spray chamber, the effect of swirl on spray dispersion becomes larger. These results can be used as a basic data for designing combustion chamber and injection system of direct injection diesel engine.

• Journal of Pharmaceutical Investigation
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• 제32권3호
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• pp.185-190
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• 2002

To improve the solubility of poorly water-soluble drug and to develop a sustained release tablets, the need for the technique, the formation of solid dispersion with polymeric materials that can potentially enhance the dissolution rate and extent of drug absorption was considered in this study. The 1:1, 1:4, and 1:5 solid dispersions were prepared by spray drying method using PVP K30, ethanol and methylene chloride. The dissolution test was carried out at in phosphate buffer solution at $37^{\circ}C$ in 100 rpm. Solid dispersed drugs were examined using differential scanning calorimetry and scanning electron microscopy, wherein it was found that felodipine is amorphous in the PVP K30 solid dispersion. Felodifine SR tablets were prepared by direct compressing the powder mixture composed of solid dispersed felodipine, lactose, Eudragit and magnesium stearate using a single punch press. In order to develop a sustained-release preparation containing solid dispersed felodipine, a comparative dissolution study was done using commercially existing product as control. The dissolution rate of intact felodipine, solid dispersed felodipine and its physical mixture, respectively, were compared by the dissolution rates for 30 minutes. The dissolution rates of felodipine for 30 minutes from 1:1, 1:4, 1:5 PVP K30 solid dispersion were 70%, 78% and 90%. However, dissolution rate offelodipine from the physical mixture was 5% of drug for 30 minutes. Our developed product Felodipine SR Tablet showed dissolution of 17%, 50% and 89% for 1, 4, and 7 hours. This designed oral delivery system is easy to manufacture, and drug releases behavior is highly reproducible and offers advantages over the existing commercial product. The dissolution rate of felodipine was significantly enhanced, following the formation of solid dispersion. The solid dispersion technique with water-soluble polymer could be used to develop a solid dispersed felodipine SR tablet.

• Journal of Pharmaceutical Investigation
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• 제38권2호
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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.

• 폴리머
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• 제39권1호
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• pp.33-39
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• 2015

올메사탄은 BCS 2단계에 해당하는 약물로 물에 잘 녹지 않는 난용성 약물이다. 이런 약물이 낮은 생체이용률과 제형을 설계하는 과정에서 어려움을 주는 원인이 된다. 본 연구에서는 올메사탄을 분무건조법 및 회전용매증 발법을 이용해 고체분산체를 제조하여 제법에 따른 난용성약물의 용출률을 확인하였다. 수용성 고분자로 PVP를 사용하여 약물과 고분자의 비율별로 고체분산체를 제조하였다. SEM을 이용하여 고체분산체의 형태학적인 특성을 분석하였고, 고체분산체의 결정학적 성질은 XRD와 DSC를 통하여 확인하였다. 또한 FTIR을 통해 화학적인 변화를 확인하고, 생체 외 용출거동 실험을 통하여 변화된 용출률을 확인하였다. 제조된 고체분산체는 pH 1.2에서 용출을 확인하였으며, 올메텍과 용출률을 비교하였으며, 분무건조를 통해 약물의 용출률을 향상시킬 수 있다는 것을 확인할 수 있다.

• Journal of Pharmaceutical Investigation
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• 제21권1호
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• pp.23-32
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• 1991

Dissolution profiles of ketoconazole in solid dispersion system (SDS) were investigated in the second fluid (pH 6.8) for the dissolution test (KPV). PVP K-30 and methyl cellulose were used as carriers in SDS, and chloroform as a solvent. Computer optimization technique was applied to obtain an optimum formula of SDS, and the following results were obtained; 1) Dissolution rate of ketoconazole in SDS was larger than that of pure ketoconazole in the second fluid of pH 6.8. 2) PVP K-30 and methyl cellulosr were good carriers for SDS of ketoconazole. Moerover PVP K-30 was better than methyl cellulose. 3) The optimum formula of ketoconazole SDS obtained from computer optimization technique was chloroform 175 ml, PVP K-30 5g and methyl cellulose 0.2g per 1g of ketoconazole. 4) The experimental value of $A_{60}$ (Amount released from ketoconazole tablet during 60 minutes) obtained from SDS by optimum formula agreed well with the value calculated by polynomial regression equation.

• Journal of Pharmaceutical Investigation
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• 제38권4호
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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.

• Journal of Pharmaceutical Investigation
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• 제28권1호
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• pp.15-23
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• 1998

Extract of Centella asiatica(ECA), which is poorly water-soluble extract from the Centella asiatica is known to express excellent wound healing properties. $ECA-{\beta}-cyclodextrin$ $(asiaticoside-{\beta}-cyclodextrin\;and\;genin-{\beta}-cyc1odextrin)$ solid dispersion system, which was prepared by freezedrying method, was formulated as gels containing poloxamer 407 and propylene glycol, and evaluated with respect to their viscosity, stability, skin permeation and drug amount in the skin of hairless mouse. The average molar ratio $asiaticoside-{\beta}-CD$ and $genin-{\beta}-CD$ was 1:1.7 and 1:22, respectively. When the molar ratio of genin and ${\beta}-CD$ was 1:5, madecassic acid made 100% solid dispersion system and asiatic acid about 65%. In dissolution study, >99% of asiaticoside from $asiaticoside-{\beta}-CD$ was dissolved in 5 minutes, and >99% madecassic acid and >64% asiatic acid from $genin-{\beta}-CD$. The apparent viscosity of poloxamer 407 gels with $ECA-{\beta}-CD$ solid dispersion system increased in proportion to poloxamer 407 and propylene glycol concentration. In the accelerated stability test, all $ECA-{\beta}-CD$ poloxamer 407 gels showed that asiaticoside was most stable and madecassic acid stable and asiatic acid similar to stability of gel with free ECA. The permeation amount of asiaticoside in poloxamer gels through hairless mouse skin decreased as the concentration of poloxamer 407 increased. When propylene glycol was added at the level of 10%, the permeation amount of asiaticoside at poloxamer gels through hairless mouse skin increased but from 15% it decreased. The permeation of asiaticoside into the skin of hairless mouse was estimated to be about $0.10\;{\mu}g/cm^2$.

• 공업화학
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• 제4권3호
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• pp.537-543
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• 1993

N-헥산과 증류수로 이루어진 비혼화성 액상계에서 교반에 의한 액-액분산을 해석하였다. 교반기는 blade형태가 flat, 60mesh와 40mesh의 금망, 그리고 60mesh금망의 외부에 금속띠를 두른 4가지의 6-bladed turbine 교반기를 사용하였다. 실험결과, 동일한 교반속도에서 유기상의 분산정도와 교반기의 소요동력은 blade형태가 flat>solid edged>60mesh>40mesh의 순서이었으며 유기상의 부피비가 증가할수록 완전분산에 필요한 최소교반속도가 증가되었다. 또한 분산상의 액적의 평균직경은 교반속도의 증가에 따라 감소하였으며 동일한 교반속도에서는 Solid edged$d_{32}$)은 다음과 같이 유기상의 부피비(${\phi}$)와 Weber number($N_{We}$)의 함수로 나타낼 수 있었다.$d_{32}/D=a(1+b{\phi})N_{We}{^{-0.6}}$.

• Bulletin of the Korean Chemical Society
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• 제35권7호
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• pp.1939-1943
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• 2014

Solid dispersion (SD) system of everolimus (EVR) with Gelucire 50/13 (Stearoyl polyoxyl-32 glycerides) was prepared using melt granulation technique with the aim of improving the physicochemical properties and dissolution rate. The solid state characterization using scanning electron microscopy and X-ray powder diffraction, indicated that the drug was homogeneously distributed in the surfactant carrier in a stable amorphous form. The dissolution rate of EVR from the optimized SD composed of the drug, Gelucire 50/13 and microcrystalline cellulose in a weight ratio of 1:5:10, was markedly rapid and higher than that from the drug powder and the market product (Afinitor$^{(R)}$, Novartis Pharmaceuticals) in all dissolution mediums tested from pH 3.0 to pH 6.8. The results of this study suggest that formulation of SD with Gelucire 50/13 using melt granulation procedure may be a simple and promising approach for improving the dissolution rate and oral absorption of the anti-cancer agent without the need for using an organic solvent.

• Archives of Pharmacal Research
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• 제28권7호
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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.