• YAKHAK HOEJI
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• v.50 no.1
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• pp.1-7
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• 2006

The purpose of the present study was to formulate the aqueous solution of 1-cyclopent-3-enylmethyl-6(3,5-dimethyl-benzoyl)-5-ethyl-1H-pyrimidine-2,4-dione (CPD), a novel antivirus compound containing pirimidine structure. For this purpose, the effects of various solubilization agents such as cosolvents [ethanol, propylene glycol (PG), polyethylene glycol 300 (PEG 300), polyethylene glycol 400 (PEG 400), glycerin], surfactants (Tween 80, Cremophor$^{(R)}$ RH40, Cremophor$^{(R)}$ EL, Poloxamer 407, Poloxamer 188) and a complexation agent [hydroxypropyl-${\beta}$-cyclodextrin (HPBCD)] , on the solubility of CPD in aqueous solution were evaluated. The solubility of CPD in water was under $1\;{\mu}g/ml$ at $20^{\circ}C$. Cosolvents such as ethanol, PG, PEG 300, PEG 400 and glycerin did not enhance the solubility of CPD at the $0{\sim}40\%$ concentration range. The solubility of CPD was significantly elevated by the addition of cosolvents over the $80\%$ concentration range. On the other hand, tween 80, Cremophor$^{(R)}$ L, Cremophor$^{(R)}$ RH40, and HPBCD showed enhanced effects on the solubility of CPD. The enhanced effects of Poloxamer 407 or Poloxamer 188 on the CPD solubility were less pronounced compared with tween 80, Cremophor$^{(R)}$ L or Cremophor$^{(R)}$ RH40. As a results, tween 80 aqueous solution was selected as an optimum solvent system. The aqueous solutions containing $20\%$ tween 80 were formulated as a dosing solution containing CPD for its intraperitoneal and intrahypodermic administration, respectively, The formular showed physical stability after stored for 7 days at $4^{\circ}C$.

• Journal of Pharmaceutical Investigation
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• v.38 no.5
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• pp.331-334
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• 2008

The objectives of this study were to formulate oral paclitaxel microemulsion and to compare the bioavailability of paclitaxel in the microemulsion formulation from the commercially available $Taxol^{(R)}$ formulation. Paclitaxel microemulsion was formulated with much less amount of Cremophor $EL^{TM}$ as compared with $Taxol^{(R)}$ to reduce severe adverse reactions produced by Cremophor $EL^{TM}$. The area under the plasma concentration-time curve from 0 hr to 24 hr ($AUC_{0-24}$), maximum plasma concentration ($C_{max}$), and relative bioavailability of palcitaxel microemulsion were increased as compared with $Taxol^{(R)}$ after oral administration. The time required to reach $C_{max}\;(T_{max})$ of palcitaxel microemulsion was significantly shorter than $Taxol^{(R)}$ following oral administration. These results suggest the faster intestinal absorption and the enhanced oral bioavailability of paclitaxel in the microemulsion formulation.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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• pp.89-89
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• 2001

Paclitaxel is currently administered i.v. as a slow infusion of a solution of the drug in an ethanol: cremophor EL: saline admixture. However, poor solubilization and toxicity are associated with this drug therapy. We have tried to develop a new surfactant for paclitaxel to improve efficacy and reduce toxicity of solubilizer. We performed the hemolysis test for chemicals which passed the paclitaxel-stabilizing test and 5 chemicals showing relatively low hemolytic effects were tested for a single dosing toxicity test. And then aceporol 330, which showed the most favorable result, was introduced to the repeated dosing toxicity tests in mouse and beagle dog. According to data based on body weight, mortality, dissection, homological test and biochemical test, Aceporol 330 exhibited much more reduced toxicity than cremophor EL.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.413.3-414
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• 2002

Paclitaxel is a diterpenoid isolated from Taxus brevifolia and is an active anticancer drug for the treatment of ovarian cancer, breast cancer and Kaposi's sarcoma. Due to its low solubility in water, it is dissolved in Cremophor EL(polyethoxylated castor oil) and ethanol, which cause serious side effects including hypersensitivity. BLK460 was developed as a novel polymeric micellar paclitaxel formulation containing Aceporol460 as solubilizer (omitted)

• Journal of Pharmaceutical Investigation
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• v.38 no.3
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• pp.171-176
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• 2008

Talniflumate is a nonsteroidal anti-inflammatory drug (NSAID), which has been used treat of rheumatoid diseases, is insoluble in water, therefore it has low bioavailability after oral administration. The purposes of this study were to prepare O/W or W/O microemulsions for solubilization of poorly water soluble drug, talniflumate and to formulate into other dosage form. For this purpose, we made O/W or W/O microemulsion with oil(soybean oil, IPM), surfactant (Cremophor $EL^{(R)}$, Tween 80) and water or propylene glycol and evaluated solubility of talniflumate. The microemulsion systems were very stable and showed transmittance above 95% without flocculation or aggregation. Especially, the solubility of talniflumate in the formulation B-1 containing 18% of isopropyl myristate and 71% of tween 80 was 10 times higher than that of other O/W microemulsions. The addition of propylene glycol and N-methylglutamine to the fomulation B-1 showed excellent capacity on the solubilization of talniflumate and the percentage was almost 2.0%. These results suggest that the microemulsion system may be promising for the solubility improvement of talniflumate.

• Journal of Pharmaceutical Investigation
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• v.37 no.5
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• pp.291-295
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• 2007

Prostaglandin $E_1\;(PGE_1)$ was formulated as two self-microemulsifying drug delivery systems (SMEDDS) composed of Cremophor $EL^{(R)}$ or Cremophor $ELP^{(R)}$ as a surfactant, ethanol as a cosurfactant and Labrafac $CC^{(R)}$ as an oil to develop liquid preparation for the treatment of erectile dysfunction. In pseudo-ternary phase diagram, viscous gel area and microemulsion area were defined. In the measurement of viscosity, the viscosity of two formulations increased gradually upon the addition of water and it decreased from the water contents over 40%. With excessive water, the present systems formed a microemulsion spontaneously. From these results, rte could expect that the present liquid $PGE_1$ SMEDDS formulations might stay within the urethra in the viscous state when contacting the moisture of the urethra and can be easily eliminated by urination. In long-term stability study, we could select one formulation more stable at the shelf storage condition of $4^{\circ}C$.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.214-217
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• 2002

Cyclosporin A (CSA) is a poorly water-soluble cyclic peptide comprising 11 amino acids. It inhibits T-lymphocyte function that plays an important role in the induction of immune response. The potent immunosuppressive activity of CSA has been used for the prevention of rejection following transplantation of liver, kidney and bone marrow, etc. The use of CSA has been often limited by several disadvantages including low bioavailability, narrow therapeutic window, nephrotoxicity, hepatotoxicity and neurotoxicity. Moreover, CSA injection is limited to patients who are unable to take the oral preparations, because it has a risk of anaphylactic shock and nephrotoxicity due to Cremophor EL$\textregistered$, a solubilizing agent used in the commercial intravenous formulation. Owing to above mentioned disadvantages of commercial products, there is a great interest in the development of the alternative dosage forms. (omitted)

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.287.3-288
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• 2002

Previously. we reported a novel polymeric micellar solubilizeI'. Aceporol 330. that showed relatively low toxic effects when it was compared with that of Cremophor EL which is currently being used for paclitaxel. In this study. we have developed a new micellar solubilizeI, Aceporol 460. that has 3-4 times higher loding capacity for paclitaxel than Aceporol 330. The single-dose and the repeated-dose toxicity of Aceporol 460 were evaluated in ICR mice. (omitted)

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.05a
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• pp.117-117
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• 2002

Paclitaxel isolated from the pacific yew tree, Taxus brevifolia, is microtuble-stabilizing agent that has a promising anticancer activity against a wide variety of tumors such as ovarian, breast and lung cancers. Because of its poor water solubility, paclitaxel is currently formulated in a mixture of polyoxyethyleneglycerol triricinoleate 35 (Cremophor EL) and dehydrated ethanol USP (1:1 v/v).(omitted)

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.174-174
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• 2001

Paclitaxel is currently administered i.v. as a slow infusion of a solution of the drug in an ethanol: cremophor EL: saline admixture. However, poor solubilization and toxicity are associated with this drug therapy. We have tried to develop a new surfactant for paclitaxel to improve efficacy and reduce toxicity of solubilizer.(omitted)