• Proceedings of the PSK Conference
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• 대한약학회 2001년도 Proceedings of International Convention of the Pharmaceutical Society of Korea
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• pp.294.1-294.1
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• 2001

• Journal of Pharmaceutical Investigation
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• 제33권2호
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• pp.85-89
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• 2003

Piroxicam-arginine complex was prepared to improve the solubility and dissolution rate of poorly water-soluble piroxicam. Its formation was identified by infrared spectrophotometry, differential thermal analysis and dissolution rate. Piroxicam complex dispersible tablets, commercial $Feldene^{\circledR}$ dispersible tablets and piroxicam physical mixture hard capsules were prepared to compare dissolution rate in water. Dissolved amounts (%) after 15 mins of piroxicam complex dispersible tablets, commercial $Feldene^{\circledR}$ dispersible tablets and piroxicam physical mixture hard capsules were 98%, 48% and 10%, respectively. The solubility of complex in water was significantly higher than that of piroxicam itself. In vivo, pharmacokinetic parameters were obtained after oral administrations of piroxicam complex and physical mixture at a does of 2 mg to New Zealand White Rabbit. The $C_{max}$ of piroxicam complex was similar to that of piroxicam. However, there were much difference between the two formulations with regard to $T_{max}$ and AUC. The $T_{max}$ of piroxicam alone was 4 hours, but that of piroxicam complex was 0.8 hours. In addition, the AUC of piroxicam complex was 1.38 times greater than that of piroxicam alone.

• Journal of Pharmaceutical Investigation
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• 제37권5호
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• pp.269-273
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• 2007

Poorly water-soluble ibuprofen and ethanol can be encapsulated in gelatin microcapsule by spray drying technique. To select an optimal formula of ibuprofen-loaded gelatin microcapsule which increased the ethanol content and ibuprofen solubility with the decreased amount of gelatin in the microcapsules, in this study, the effect of gelatin, ibuprofen and sodium lauryl sulfate on the ibuprofen solubility and the amount of ethanol and ibuprofen encapsulated in the gelatin microcapsule were investigated. Ibuprofen solubility and the amount of ethanol encapsulated increased as gelatin and sodium lauryl sulfate increased, reached maximum at 4% and 0.6%, respectively and then followed a rapid decrease. Furthermore, the ibuprofen solubility and the encapsulated ibuprofen content increased as the amount of ibuprofen increased, reaching maximum at 0.5% and beyond that, there was no change in the solubility and ibuprofen content. However, the encapsulated ethanol content remained same irrespective of the amount of ibuprofen. On the basis of increased ibuprofen solubility, our results showed that the formula of ibuprofen-loaded gelatin microcapsule at the ratio of gelatin/ibuprofen/sodium lauryl sulfate/water/ethanol of 4/0.5/0.6/30/70 with ibuprofen solubility of about $290\;{\mu}g/mL$ and ethanol content of about $160\;{\mu}g/mg$ could be a potential oral delivery system for poorly water-soluble ibuprofen.

• 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.

• Proceedings of the PSK Conference
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-1
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• pp.44-46
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• 2003

Although Cyclosporin A (CsA) is a powerful immunosuppresant with little adverse effect on the bone marrow, CsA administered orally in the general formulation cannot obtain high bioavailability due to its poor aqueous solubility. To improve the solubility and enhance the bioavailability of poorly water-soluble CsA, many different approaches have been made in our laboratory. (omitted)

• Journal of Pharmaceutical Investigation
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• 제38권2호
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• pp.127-134
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• 2008

Peroral administration is the most convenient one for the administration of pharmaceutically active compounds. Most of poorly water-soluble drugs administered via the oral route, however, remain poorly available due to their precipitation in the gastrointestinal (GI) tract and low permeability through intestinal mucosa. In this study, one of drug delivery carriers, lipid nanoparticles (LNPs) were designed in order to reduce side effects and improve solubility and stability in GI tract of the poorly water soluble drugs. However, plain LNPs are generally unstable in the GI tract and susceptible to the action of acids, bile salts and enzymes. Accordingly, the surface of LNPs was modified with polyethylene glycol (PEG) for the purpose of improving solubility and GI stability of paclitaxel (PTX) in vitro. PEG-modified LNPs containing PTX was prepared by spontaneous emulsification and solvent evaporation (SESE) method and characterized for mean particle diameter, entrapping efficiency, zeta potential value and in vitro GI stability. Mean particle diameter and zeta potential value of PEG-modified LNP containing PTX showed approximately 86.9 nm and -22.9 mV, respectively. PTX entrapping efficiency was about 70.5% determined by UV/VIS spectrophotometer. Futhermore, change of particle diameter of PTX-loaded PEG-LNPs in simulated GI fluids and bile fluid was evaluated as a criteria of GI stability. Particle diameter of PTX-loaded PEG-LNPs were preserved under 200 nm for 6 hrs in simulated GI fluids and bile fluid at $37^{\circ}C$ when DSPE-mPEG2000 was added to formulation of LNPs above 4 mole ratio. As a result, PEG-modified LNPs improved stability of plain LNPs that would aggregate in simulated GI fluids and bile solution. These results indicate that LNPs modified with biocompatible and nontoxic polymer such as PEG might be useful for enhancement of GI stability of poorly water-soluble drugs and they might affect PTX absorption affirmatively in gastrointestinal mucosa.

• Journal of Pharmaceutical Investigation
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• 제29권1호
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• pp.37-45
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• 1999

ABSTRACT-A self-microemulsifying drug delivery system (SMEDDS) was developed to enhance the solubility and dissolution rate of poorly water soluble drug, biphenyl dimethyl dicarboxylate, DDB. The system was optimized by evaluating the solubility of DDB and the microemulsion existence range after the preparation of microemulsions with varying compositions of triacetin and surfactant-cosurfactant mixtures (Labrasol as surfactant (S) and the combination of Transcutol, Cremophor RH 40 and Plurol oleique as cosurfactant (CoS)). SMEDDS in this study markedly improved the solubility of DDB in water up to 10 mg/ml and the size of the o/w microemulsion droplets measured by dynamic light scattering showed a narrow monodisperse size distribution with an average diameter less than 50 nm. The microemulsion existing range is increased proportional to the ratio of S/CoS, however, it decreased remarkably as the oil content was more than 20%. In vitro dissolution study of SMEDDS showed a significantly increased dissolution rate of DDB in water (> 12 fold over DDB powder), and SMEDDS also had significantly greater permeability of DDB in Caco-2 cell compared to powders.

• Journal of Pharmaceutical Investigation
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• 제40권3호
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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.

• Archives of Pharmacal Research
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• 제18권1호
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• pp.22-26
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• 1995

The solubility and dissolution rate of naproxen (NPX) complexed with 2-hydroxypropyl-.betha.-cyc-lodextrin (2-HP.betha.CD) using coprecipitation, evaporation, freeze-drying and kneading method were investigated. Solubility of NPX linearly increased (correlation cefficient, 0.995) as $2-HP\betaCD$ concentraction increased, resutling in $A_l$ type phase solubility curve. Inclusion complexes prepared by four different methods were compared by different methods were compared by dfferential scanning calorimetry(DSC). The NPX showed sharp endothemic peak around $156^{\circ}C$ but inclusion complexes by evaporation, freeze-drying and kneading method showed very broad peak without distinct phase transtion temperature. In contrast, inclusion complex prepared by coprecipitation method resulted in detectable peak around $156^{\circ}C$ which is similar to NPX, suggesting incoplete formation of indusion co plex. Dissolution rate of inclusion complexes prepared by evaporation, frezz-drying and kneding except coprecipitation method was largely enhanced in the simultaed gastric and intestinal fluid when compared to NPX powder and commercial $NA-XEN^\registered$tablet. However, about 65% of NPX in gstric fluid. in case of inclusion complex prepared by coprecipitation method, formation of inclusion complex appeared to be incoplete, resulting in no marked enhancement of dissolution rate. From these findings, inclusion complexes of poorly water-soluble NPX with $2-HP\betaCD$ were useful to increase soubility and dissolution rate, resting in enhancement of bioavailability and minimization of gastrointestinal toxicity of drug upon oral administration of inclusion complex.

• Polymer(Korea)
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• 제35권4호
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• pp.277-283
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• 2011

Solid dispersion is mainly used for improved dissolution of poorly water-soluble drugs. Solid dispersion of pranlukast was prepared by spray-drying with plasdone S-630. When pH of water was high, pranlukast was highly soluble in the solubility experiment of solid dispersions with varying pH. The particle size of pranlukast particles in solid dispersions was measured to be in nanometers scale based on particle size analysis. Zeta-potential analysis confirmed the negative charge of solid dispersion. SEM was used to observe the surface of solid dispersion, which confirmed spherical morphology, DSC and XRD confirmed the amorphous nature of solid dispersions. The in vitro test was carried out to find improved dissolution rate of pranlukast solid dispersion in simulated juice gastric and a controlled experiment was carried out to compare pranlukast solid dispersions with a conventional drug (Onon$^{(R)}$), These results showed the dissolution properties of pranlukast solid dispersions prepared by spray drying proper for the oral pharmaceutical formulation.