• Journal of Pharmaceutical Investigation
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• 제25권2호
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• pp.129-136
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• 1995

In order to reduce the systemic side effects and the gastrointestinal irritation of indomethacin following its oral administration, the drug was formulated as a transdermal gel using poloxamer 407. In vitro diffusion cells fitted with excised rat skins were used to evaluate the effects of formulation variables on skin permeation of indomethacin from poloxamer gels. The formulation variables were the concentrations of indomethacin, poloxamer 407 and ethanol, and the gel pH. The increase of the drug amount in the gel from 0.5% to 2.0% induced a direct but nonlinear increase in the skin permeation rate of indomethacin. The increase of poloxamer concentration from 17.5% to 25% in the gel resulted in a decrease of skin permeation rate of indomethacin, which was due to a reduction in the amount of free drug molecules available for permeation through skin by entrapping more drug molecules within the micelles formed by poloxamer. The increase of ethanol concentration from 10% to 20% in the gel resulted in a linear increase of permeation rate of indomethacin through skin, possibly due to the penetration enhancing effect of ethanol. The skin permeation of indomethacin was substantially influenced by the gel pH, exhibiting a maximum at pH 4.

• Journal of Pharmaceutical Investigation
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• 제32권4호
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• pp.305-311
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• 2002

In order to evaluate the effect of poloxamer 407 content on the dissolution profiles of pellets, diltiazem HCl (DTL) core pellets were prepared with poloxamer 407 (50-90% w/w, with lactose as filler) using an extruder and a spheronizer. Any possible interaction between the drug and excipients was evaluated using DSC, IR and TLC. Dissolution tests were performed using USP basket method. In addition, scanning electron micrograph was performed to examine the surface roughness and cross sections. The release of DTL from the core pellets was decreased with increasing poloxamer 407 content. Cracks appeared on the surface of the core pellets with increasing the poloxamer 407 content, which may play a role on the retardation of the release of DTL from core pellets. There was no any significant interaction between the drug and excipients employed to prepare the core pellets.

• Archives of Pharmacal Research
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• 제26권11호
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• pp.973-978
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• 2003

A polymeric film composed of Carbopol, Poloxamer and hydroxypropyl methylcellulose was prepared to develop a buccal patch and the effects of composition of the film on adhesion time, swelling ratio, and dissolution of the film were studied. The effects of plasticizers or penetration enhancers on the release of triamcinolone acetonide (TAA) were also studied. The hydrogen bonding between Carbopol and Poloxamer played important role in reducing swelling ratio and dissolution rate of polymer film and increasing adhesion time. The swelling ratio of the composite film was significantly reduced and the adhesion time was increased when compared with Carbopol film. As the ratio of Poloxamer to hydroxypropyl methylcellulose increased from 0/66 to 33/33, the release rate of TAA decreased. However, no further significant decrease of release rate was observed beyond the ratio of 33/33. The release rate of TAA in the polymeric film containing polyethylene glycol 400, a plasticizer, showed the highest release rate followed by triethyl citrate, and castor oil. The release rate of TAA from the polymeric film containing permeation enhancers was slower than that from the control without enhancers. Therefore, these observations indicated that a preparation of a buccal patch is feasible with the polymeric film composed of Cabopol, Poloxamer and hydropropyl methylcellulose.

• 약학회지
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• 제41권1호
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• pp.22-29
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• 1997

Poloxamer-poly (acrylic acid) (PAA) interpenetrating polymer networks (IPNs) were prepared via matrix polymerization of acrylic acid with poloxamer prepolymer. The equilibrium s welling of poloxamer/PAA IPNs was determined in various pH medium. The swelling of poloxamer/PAA IPNs was more affected by pH difference compared with the swelling of homo PAA gel due to protonation and deprotonation of the PAA network, followed by reversible formation and dissociation of the interpolymer complex due to hydrogen bonding between acidic hydrogens and ether oxygens. Nonionic/anionic/cationic drugs were incorporated into IPN matriceds as a model drug and their release behavior was studied. Nonionic, drug revealed release patterns depending solely on pH dependent swelling kinetics. In contrast, the release of ionic drugs was significantly affected by ionic drug-polymer interaction as well as the swelling kinetics.

• 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 $0.10\;{\mu}g/cm^2$.

• Journal of Pharmaceutical Investigation
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• 제37권1호
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• pp.1-5
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• 2007

Solid dispersions of piroxicam were prepared by melting method using poloxamer as a carrier. The results of DSC and XRD studies showed that the amorphous farm of piroxicam coexisted with the crystalline form in the solid dispersions. However, the ratio of crystalline form of piroxicam in the solid dispersion prepared by melting method decreased in comparison with the same ratio of the solid dispersion prepared by solvent method. As the ratio of poloxamer in the solid dispersion increased, the ratio of the amorphous form of piroxicam in the solid dispersion increased. The dissolution rate of piroxicam from the solid dispersions was significantly higher than that from piroxicam powder. In comparison to the solid dispersion prepared by solvent method, the dissolution rate of piroxicam from the solid dispersion prepared by melting method was higher. As the ratio of poloxamer in the solid dispersion prepared by melting method increased, the initial dissolution rate decreased, however, the total amount dissolved at the end of the study increased.

• Journal of Pharmaceutical Investigation
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• 제26권4호
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• pp.263-271
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• 1996

Sulconazole nitrate(SCN), an imidazole derivative which has been effective in the treatment of dermatophytosis, tinea versicolor and candidiasis, was formulated as a gel containing drug, poloxamer 407, ethanol and propylene glycol. The resulting SCN gels were evaluated with respect to their viscosity, drug release rate, skin permeation rate. The apparent viscosity of SCN gel increased in proportion to poloxamer 407, drug and propylene glycol concentration. In case ethanol was added, the apparent viscosity decreased. The drug release rate of SCN gel increased in proportion to temperature and ethanol concentration. But the drug release rate decreased as the concentration of poloxamer 407 increased. The increase of drug concentration induced nonlinear increase of drug release rate. When propylene glycol was added at the level of 10%, the drug release rate increased but from 15% it decreased. The skin permeation rate decreased in high concentration of poloxamer 407. The skin permeation rate of SCN gel containing 15% ethanol increased about twice than that of gel without ethanol. The increase of drug concentration induced nonlinear increase of skin permeation rate. When propylene glycol was added at the level of 10%, the skin permeation rate increased but from 15% it decreased.

• Archives of Pharmacal Research
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• 제26권8호
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• pp.653-658
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• 2003

It has been reported that at low temperature region, poloxamers existed as a monomer. Upon warming, an equilibrium between unimers and micelles was established, and finally micelle aggregates were formed at higher temperature. In this study, the fluorescence spectroscopy was used to study the micelle formation of the poloxamer 407 in aqueous solution. The excitation and emission spectra of pyrene, a fluorescence probe, were measured as a function of the concentration of poloxamer 407 and temperature. A blue shift in the emission spectrum and a red shift in the excitation spectrum were observed as pyrene transferred from an aqueous to a hydrophobic micellar environment. From the $I_1/I_3 and I_{339}/I_{333}$ results, critical micelle concentration (cmc) and critical micelle temperature (cmt) were determined. Also, from the fluorescence spectra of the probe molecules such as 8-anilino-1-naphthalene sulfonic acid and 1-pyrenecarboxaldehyde, the blue shift of the $\lambda_{max}$ was observed. These results suggest a decrease in the polarity of the microenvironment around probe because of micelle formation. The poloxamer 407 above cmc strongly complexed with hydrophobic fluorescent probes and the binding constant of complex increased with increasing the hydrophobicity of the probe.

• Journal of Pharmaceutical Investigation
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• 제24권3호spc1호
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• pp.27-32
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• 1994

In order to reduce systemic side effects following oral administration, flurbiprofen was formulated as transdermal gels consisting of the drug, poloxamer 407 and ethanol in buffer solutions. The effect of formulation variables in the preparation of flurbiprofen gels on skin permeation of the drug was evaluated using Keshary-Chien diffusion cells fitted with excised rat skins. The permeation rate of flurbiprofen through rat skin was directly proportional to initial drug concentration (between 0.1% and 1.0%) in the gel while it was inversely proportional to poloxamer 407 concentration (between 17.5% and 25%). The skin permeation of flurbiprofen was substantially influenced by the gel pH between 3 and 7, exhibiting a maximum at pH 4. The concentration effect of ethanol on the permeation of the drug was negligible in the concentration range of $10{\sim}20%$.

• Journal of Pharmaceutical Investigation
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• 제19권2호
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• pp.109-116
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• 1989

Solid dispersion of fenticonazole nitrate (FN) with poloxamer 407, polyethylene glycol 6000, povidone (K-90) were prepared by the solvent method. To characterize the state of the drug in solid dispersions, the x-ray diffractometry and differential scanning calorimetry were carried out. The identification of these systems suggested that FN in the poloxamer 407 system remained in crystalline state, and the drug in the PVP system was amorphous. A marked increase in the dissolution rate of FN was attained by dispersing the drug in the hydrophilic polymers used, and the dispersion with poloxamer 407 was superior to the other two carriers in releasing the drug into solution.