• Journal of Pharmaceutical Investigation
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• 제34권2호
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• pp.91-94
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• 2004

To develop a poloxamer-based solid suppository with poloxamer mixtures, the melting points of various formulations composed of P 124 and P 188 were investigated. To investigate the effect of poloxamer to the dissolution ad dissolution mechanism of diclofenac sodium from the suppository the dissolution of diclofenac sodium delivered by the poloxamer-based suppository was performed. Furthermore, to investigate the mucoadhesive property of the poloxamer-based sold suppository, the identification test in the rectum was carried out after its rectal administration in rats. The poloxamer mixtures composed of P 124 and P 188 were homogeneous. Ver small amounts of P 188 affected the melting points of poloxamer mixtures. In particular, the poloxamer mixture [P 124/P 188 (97/3%)] with the melting point of about $32^{\circ}C$ was a sold for at room temperature and instantly melted at physiological temperature. Furthermore, very small amounts of P 188 in the poloxamer-based suppository hardly affected the dissolution rates of diclofenac sodium from the suppository. Dissolution mechanism analysis showed the dissolution of diclofenac sodium was proportional to the time. At 4 h after administration, the blue colo of poloxamer-based suppository [diclofenac sodium/poloxamer mixture (2.5/97.5%)] with the P 124/ P 188 ratio of (97/3%) and blue lake in the rectum was faded. However, the position of suppository in the rectum did not significantly change with time. Thus, it retained in thε rectum for at least 4 h. Our results indicated that the poloxamer-based sold suppository with P 124 and P 188 would be a candidate of rectal dosage form for diclofenac sodium.

• Journal of Pharmaceutical Investigation
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• 제33권1호
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• pp.57-60
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• 2003

To enhance the solubility of poorly water-soluble ibuprofen with poloxamer and menthol, the effects of menthol and poloxamer 188 on the aqueous solubility of ibuprofen were investigated. In the absence and presence of additives such as ethanol and poloxamer 188, the solubility of ibuprofen increased until the ratio of menthol to ibuprofen increased from 0:10 to 4:6 followed by an abrupt decrease in solubility above the ratio of 4:6, indicating that 4 parts of ibuprofen formed eutetic mixture with 6 parts of menthol. In the presence of poloxamer, the solutions with the same ratio showed abrupt increase in the solubility of ibuprofen. Furthermore, in the presence of poloxamer, the solution with ratio of 4:6 showed more than 2.5- and 6-fold increase in the solubility of ibuprofen compared with that without additives and that without menthol, respectively. The solution with menthol/ibuprofen ratio of 1:9 and higher than 15% poloxamer 188 showed the maximum solubility of ibuprofen, 1.2 mg/ml. Thus, menthol gave the greatly enhanced solubility of ibuprofen with poloxamer 188.

• Journal of Pharmaceutical Investigation
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• 제38권5호
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• pp.289-293
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• 2008

To develop a poloxamer-based solid suppository with poloxamer and polyethylene glycol mixtures, the melting point of various formulations composed of P 188 and propylene glycol were investigated. The dissolution and antitumor activity of clotrimazole delivered by the poloxamer-based suppository were performed. The poloxamer mixtures composed of P 188 and propylene glycol were homogeneous phases. P 188 greatly affected the melting point of poloxamer mixtures. In particular, the poloxamer mixture [P 188/propylene glycol(70/30%)] with the melting point of about $32^{\circ}C$ was a solid form at room temperature and instantly melted at physiological temperature. Furthermore, the ratio of P 188/propylene glycol greatly affected the dissolution rates of clotrimazole from poloxamer-based suppository. It gave the more effective anti-tumor activity than conventional PEG-based suppository due to fast dissolution. Thus, the clotrimazole-Ioaded poloxamer-based solid suppository was an effective rectal dosage form with anti-tumor activity.

• Journal of Pharmaceutical Investigation
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• 제35권2호
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• pp.107-110
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• 2005

To develop a clotrimazole-loaded solid suppository with poloxamer and propylene glycol, the melting points of various formulations composed of poloxamer 188 (P 188) and propylene glycol were investigated. The dissolution study of clotrimazole delivered by the suppository composed of P 188 and propylene glycol was performed. The mixtures composed of P 188 and propylene glycol were homogeneous. Propylene glycol affected the melting points of poloxamer mixtures. In particular, the mixture [P 188/propylene glycol (70/30%)] with the melting point of about $32^{\circ}C$ was a solid form at room temperature and instantly melted at physiological temperature. Furthermore, propylene glycol affected greatly the dissolution rates of clotrimazole from the suppository. Dissolution mechanism analysis showed the dissolution of clotrimazole was proportional to the time. Our results indicated that the solid suppository with P 188 and propylene glycol would be a candidate of rectal dosage form for clotrimazole.

• Journal of Pharmaceutical Investigation
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• 제37권1호
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• pp.39-43
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• 2007

Previously, we have reported that PLGA nanoparticles were prepared for sustained release of water-soluble blue dextran and the particle size, in vitro release pattern and encapsulation were modulated by varying polymers. This study was designed to encapsulate plasmid DNA in PLGA nanoparticles and to investigate the effect of Polymers and temperatures. PLGA nanoparticles were fabricated with poloxamer 188 (P188) or poloxamer 407 (P407) by using spontaneous emulsification solvent diffusion method. As a model plasmid DNA, pCMV-Taq2B/1L-18 was encapsulated in PLGA nanoparticles. Then, the particle size, zeta potential and encapsulation efficiency of nanoparticles containing plasmid DNA were investigated. Particle sizes of PLGA nanoparticles prepared with P188 and P407 were in the range of 200-330 nm and 250-290 nm, respectively. Zeta potentials of nanoparticles were negative regardless of nanoparticle compositions. Encapsulation efficiency of P407 nanoparticles prepared at $30^{\circ}C$ was higher than those at other preparation condition. From the results, the PLGA nanoparticles prepared with poloxamers at different temperature, could modulate the particles size of nanoparticles, and encapsulation efficiency of plasmid DNA.

• 약학회지
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• 제50권1호
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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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• 제34권5호
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• pp.385-391
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• 2004

The purpose of the present study was to formulate the aqueous solution of $20-O-{\beta}-D-glucopyranosyl-20(S)-protopanaxadiol\;(IH-901)$, an intestinal bacterial metabolic derivative from Ginseng protopanaxadiol saponin. 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 $(Tween\;80,\;Cremophor^{\circledR}\;RH40,\;Cremophor^{\circledR}\;EL,\;Poloxamer\;407,\;Poloxamer\;188)$ and a complexation agent $[hydroxypropyl-{\beta}-cyclodextrin\;(HPBCD)]$, on the solubility of IH-90l in aqueous solution were evaluated. The solubility of IH-901 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 IH-901 at the 0 - 40% concentration range. The solubility of IH-901 was significantly elevated by the addition of cosolvents over the 80% concentration range. On the other hand, tween 80, $Cremophor^{\circledR}\;EL,\;Cremophor^{\circledR}\;RH40$ and HPBCD showed enhanced effects on the solubility of IH-901. The enhanced effects of Poloxamer 407 or Poloxamer 188 on the IH-901 solubility were less pronounced compared with $Cremophor^{\circledR}\;EL\;or\;Cremophor^{\circledR}\;RH40$. As a results, $Cremophor^{\circledR}$ aqueous solution was selected as an optimum solvent system. The aqueous solutions containing 10% $Cremophor^{\circledR}\;EL$ and 7% $Cremophor^{\circledR}\;RH40$ were formulated as dosing solutions containing 5.0 mg/ml of IH-901 for its intravenous and oral administration, respectively. The formular showed physical stability after stored for 7 days at $4^{\circ}C$.

• Journal of Pharmaceutical Investigation
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• 제36권2호
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• pp.109-114
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• 2006

Biodegradable poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles were developed for sustained delivery of water-soluble macromolecules. PLGA nanoparticles were fabricated by spontaneous emulsification solvent diffusion method generating negatively charged particles and heterogeneous size distribution. As a model drug, blue dextran was encapsulated in PLGA nanoparticles. In addition, nanoparticles were also prepared with varying ratio of poloxamer 188 (P188) and poloxamer 407 (P407), and coating with poly(vinyl alcohol) (PVA). Then, the particle size, zeta potential and encapsulation efficiency of nanoparticles containing blue dextran were studied. In vitro release of blue dextran from nanoparticles was also investigated. The surface and morphology of nanoparticles were characterized by scanning electron microscopy (SEM). In case of nanoparticles prepared with PLGA, P407, and different organic solvents, particle size was in the range of $230{\sim}320\;nm$ and zeta potentials of nanoparticles were negative. The SEM images showed that ethyl acetate is suitable for the formulation of PLGA nanoparticles with good appearance. Moreover, ethyl acetate showed higher encapsulation efficiency than other solvents. The addition of P188 to formulation did not affect the particle size of PLGA nanoparticles but altered the release patterns of blue dextran from nanoparticles. However, PVA, as a coating material, altered the particle size with increasing the PVA concentration. The nanoparticles were physically stable in the change of particle size during long-term storage. From the results, the PLGA nanoparticles prepared with various contents of poloxamers and PVA, could modulate the particles size of nanoparticles, in vitro release pattern, and encapsulation of water-soluble macromolecules.

• KSBB Journal
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• 제24권6호
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• pp.533-540
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• 2009

본 연구에서는 난용성 약물인 5'-NIO의 가용화를 위해 초임계 유체 ASES 공정을 이용하여 PVP K-30과의 고체분산체를 제조하고 첨가제인 P188의 영향에 대해 고찰하였다. FE-SEM을 이용하여 초임계 유체 공정으로 제조된 고체분산체 미립자의 형상을 분석한 결과 100-200 nm 크기의 나노입자들이 응집된 형태를 나타내었으며, P188의 함량이 증가함에 따라 입자간의 응집이 증가하여 덩어리 형태로 전환되는 것을 확인할 수 있었다. XRD 분석 결과 5'-NIO 결정피크가 사라진 것을 확인하였으며, 이는 5'-NIO가 고분자 매질내에 분자 또는 나노 크기 수준으로 분산되었음을 의미한다. 또한 FT-IR 분석 결과 5'-NIO와 PVP K-30간에 수소결합과 같은 상호작용이 존재함을 학인할 수 있었다. 5'-NIO/PVP K-30 2성분계 고체분산체에 비이온성 계면활성제를 첨가한 경우 용출률이 현저히 향상되었으나, P188의 함량이 매우 큰 경우에는 오히려 용출률이 감소한 다는 것을 확인하였다. 본 연구를 통해 초임계 유체 공정이 기존의 고체분산체 제조 방법을 충분히 대체할 수 있다는 가능성을 확인할 수 있었다.

• 약학회지
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• 제42권3호
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• pp.290-295
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• 1998

To optimize the formulation of acetaminophen liquid suppository, the effect of additives on the physicochemical properties of liquid suppository base was investigated. The physi cochemical properties of P 407/P 188 (15/15%) (abbreviated in 15/15) and P 407/P l88 (15/20%) (abbreviated in 15/20) were measured after the addition of following additives; 2.5% acetaminophen as an active ingredient, vehicle components (5% ethanol, 5% propylene glycol, 5% glycerin), preservatives (0.1% sodium benzoate, 0,1% methylparahydroxybenzoate, 0.1% propylparahydroxybenzoate) and 1% of sodium chloride as an ionic strength controlling agent. Poloxamer gel was prepared with three different buffer solutions (pH 1.2, 4.0 and 6.8) and the physicochemical properties, gelation temperature, gel strength and bioadhesive force, were determined. In the results, the effect of additives on the physicochemical properties was dependent on their bonding capacities including hydrogen bonding and cross-linking bonding. Because the hydrogen-bonding capacities of acetaminophen, ethanol and propylene glycol were smaller than that of poloxamer, the binding force of poloxamer gel became weak by their putting in between poloxamer gel. Therefore, the gelation temperature (15/15, $35.7^{\circ}C$ vs 37.0, 39.4 $38.2^{\circ}C$; 15/20, $29.2^{\circ}C$ vs 31.2, 32.0, $30.3^{\circ}C$) increased, and gel strength (15/15, 4.03 see vs 2.72, 2.08, 3.12sec; 15/20, 300g vs 50, 50, 200g) and bioadhesive force (15/15, $6.8{\times}10^2\;dyne/cm^2$ vs 3.2, 6.0, $6.0{\times}10^2\;dyne/cm^2$; 15/20, $97.3{\times}10^2\;dyne/cm^2$ vs 11.1, 89.5, $92.0{\times}10^2\;dyne/cm^2$) decreased. Furthermore, the binding force of poloxamer gel became strong due to the hydrogen-bonding capacities of glycerin and the cross-liking bonding of sodium salt. Then, the gelation temperature (15/15, 35.0, $32.1^{\circ}C$; 15/20, 26.0, $21.0^{\circ}C$) decreased, and gel strength (15/15, 6.51 see, 300g; 15/20, 500, 650g) and bioadhesive force (15/15, 7.2, $81.6{\times}10^2\;dyne/cm^2$; 15/20, 112.3, $309.2{\times}10^2\;dyne/cm^2$) increased. The effect of pH on the physicochemical properties of poloxamer gel was dependent on the ingredients with which the buffer solutions were prepared. Poloxamer gels prepared with pH 1.2 and 4.0 buffer solutions had the increasing gelation temperature (15/15, 37.5, $38.1^{\circ}C$; 15/20, 33.1, $34.0^{\circ}C$) and the decreasing gel strength (15/15, 2.98, 3.81sec; 15/20, 200, 200g) and bioadhesive force (15/15, $7.0{\times}10^2dyne/cm^2$; 15/20, $74.0{\sim}88.1{\times}10^2dyne/cm^2$) owing to HCl. Poloxamer gel prepared with pH 6.8 buffer solutions had the decreasing gelation temperature (15/15, $27.2^{\circ}C$; 15/20, $22.3^{\circ}C$) and the increasing gel strength (15/15, 400g; 15/20, 550g) and bioadhesive force (15/15, $207.0{\times}10^2dyne/cm^2$; 15/20, $215.0{\times}10^2dyne/cm^2$) due to the cross-linking bonding of $NaH_2PO_4\;and\;K_2HPO_4$.