• YAKHAK HOEJI
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• v.41 no.5
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• pp.607-614
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• 1997

Flurbiprofen- and flurbiprofen axetil-loaded microemulsions composed of soybean oil, poloxamer 407, glycerine and water were prepared by generator-type homgenizer and ultrasoni c probe system. The particle size of microemulsions was measured by the dynamic light scattering method. The pharmacokinetics and organ distribution of flurbiprofen were investigated after intravenous injection of flurbiprofen solution, flurbiprofen-loaded microemulsion and flurbiprofen axetil-loaded microemulsions equivalent to 10mg/kg of flurbiprofen to rats. Blood samples were collected from the anterior ciliary artery of rats for 24hr, and flurbiprofen in plasma and organs was analyzed by HPLC. Stable microemulsions were prepared. Even though there is a little change in droplet size just after the preparation, no creaming and no separation were occured during the storage period for 6 months at 4, 21, 37 and 45$^{\circ}C$. Pharmacokinetic parameters and organ distribution of flurbiprofen after intravenous injection of flurbiprofen- and flurbiprofen axetil-loaded microemulsions emulsified with poloxamer 407 were not significantly different from those of commercial lipid microemulsion emulsified with lecithin. Therefore, it is concluded that flurbiprofen- and flurbiprofen axetil-loaded microemulsion prepared with poloxamer 407 could be used as a parenteral formulation.

• YAKHAK HOEJI
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• v.43 no.4
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• pp.447-457
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• 1999

The purpose of this study is to prepare the adhesive type patch containing flurbiprofen, and to demonstrate the feasibility of flurbiprofen administration through the intact skin using adhesive type patch preparation. For this purpose, two pressure sensitive adhesives, Polyisobutylene(PIB) and $Gelva^{\circledR}737$, were selected from the chemical grade of polymers, and the adhesive type patches of flurbiprofen were prepared. The release rate of flurbiprofen from the PIB-based adhesive patch was higher than that from $Gelva^{\circledR}737$ based adhesive patch. The release rate of flurbiprofen from the PIB-based A-type patch with 1.0mm, 1.5mm or 2.0mm thicknesses followed the first order kinetics. In the skin permeation study, using male hairless mouse skin, a monophasic skin permeation profile was observed with 1% flurbiprofen loading dose. The inclusion of palmitic acid or SLS(0.25~0.5%) as an enhancer produced a remarkable enhancement in the skin permeation rate of flurbiprofen, and the percentile ratio of drug and enhancer appeared to be important for the effective enhancement. In the in vivo percutaneous absorption study, the plasma concentration of the optimal formulation was significantly (p<0.01) higher than that of the conventional cataplasma ($Bifen^{\circledR}$). These studies demonstrate a good feasibility of flurbiprofen administration through the intact skin using a transdermal patch, and show a possibility of the development of flurbiprofen patches.

• Journal of Pharmaceutical Investigation
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• v.15 no.3
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• pp.100-112
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• 1985

Dissolution characteristics of flurbiprofen solvent deposited on ${\alpha}-cyclodextrin$, ${\beta}-cyclodextrin$, lactose and corn starch were studied to evaluate the pharmaceutical aspects of solvent deposition method where drug was solvent deposited on the surface of excipients. In a solvent deposition system, the drug to excipient ratio and kind of excipient affect much on dissolution rates of flurbiprofen. The solvent deposition system formation was confirmed by scanning electron microscope. By increasing the amounts of matrix, it was possible to enhance the dissolution rate of flurbiprofen solvent deposition system. The amount of flurbiprofen dissolved from ${\beta}-cyclodextrin$ deposition system (1:10) at 60 minutes was enhanced 6.5 times in water and 28 times in simulated gastric juice compared with flurbiprofen alone. Flurbiprofen solvent deposited system (1:10) enhanced dissolution rate greater than inclusion complex and dispersion system.

• Archives of Pharmacal Research
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• v.17 no.4
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• pp.240-243
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• 1994

Release rates of flurbiprofen from transdermal gels made of poloxamer 407 were evaluated using a membraneless diffusion cell in order to study the effects of formulation variables on flurbiprofen release such as poloxamer 407 (17.5-25%) drug (0.1-1.0%), ethanol (10-20%), PG or PEF 300 (5-15%) concentrations and gel pH(3-7). Isopropyl myristate was employed as a receptor medium for the drug released from the gel. The diffusion coefficient of flurbiprofen decreased linearly as the amount of poloxamer 407 and the drug in the gel increased. The release rate of flurbiprofen was gel increased. The The addition of more ethanol in the gel increased the drug release, resulting from the increase of the thermodynamic activity of the drug in the aqueous phase of the gel. However, the concentration effects of PG and PEG 300 on the release rate of flurbiprofen were negligible over the concentration range used.

• Journal of Pharmaceutical Investigation
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• v.24 no.3
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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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• v.25 no.2
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• pp.125-128
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• 1995

To increase the skin permeation rate of flurbiprofen, fatty alcohols were added in propylene glycol vehicle containing 1% flurbiprofen. Their enhancing effect on the skin permeation of flurbiprofen was evaluated using Keshary-Chien diffusion cells fitted with excised rat skins. Lauryl alcohol and oleyl alcohol increased the skin permeation rate of flurbiprofen 11.3 and 8.5 fold, respectively, compared to the control vehicle.

• YAKHAK HOEJI
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• v.39 no.2
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• pp.185-192
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• 1995

Flurbiprofen, one of potent nonsteroidal antiinflammatory drugs, has several systemic side effects due to dose dumping effect following oral administration of its conventional solid dosage forms. To reduce these side effects and to sustain therapeutic concentration of the drug, matrix tablets of flurbiprofen were prepared and evaluated for sustained release from the tablets. The matrix tablets of flurbiprofen were prepared with Eudragit, Pluronic, (anhydrous) lactose and colloidal silicon dioxide employing two different preparation methods, wet granulation and direct compression. The dissolution rates of the tablets were evaluated using KP 2 method. Formulation factors that affected dissolution rates of flurbiprofen were the type and content of Eudragit, the type and content of Pluronic, and the tablet preparation method. Several formulations of the matrix tablets showed dissolution patterns close to the simulated profile using pharmacokinetic parameters of flurbiprofen.

• Journal of Periodontal and Implant Science
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• v.26 no.1
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• pp.317-333
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• 1996

The main goal of periodontal regeneration is to be achieved by epithelial exclusion, periodontal ligament cell activation or alveolar bone regeneration. The purpose of this study was to investigate on the physico- chemical and biological characteristics of biodegradable chitosan beads. Chitosan beads were fabricated by ionic gelation with sodium tripolyphosphate and they had the size in 300um diameter. As therapeutic agent, flurbiprofen was incorporated into the beads by 10, 20% loading contents. The release of drugs from the chitosan beads was measured in vitro. Also, biological activity tests of flurbiprofen loaded chitosan beads including cytotoxicity test, ihhibition of $IL-1{\beta}$ production, suppression to $PGE_2$ production, collagenase inhibition test, the ability of total protein synthesis, and tissue response were evaluated. The amount of flurbiprofen released from chitosan was 33-50% during 7 days. Minimal cytotoxicity was observed in chitosan beads. Flurbiprofen released from chitosan beads significantly suppressed the $IL-1{\beta}$ production of monocyte, $PGE_2$ production and markedly inhibited collagenase activity. Meanwhile, flurbiprofen released from this system showed increased ability for protein synthesis. Throughout 4 -week implantation period, no significant inflammatory cell infiltrated around chitosan bead and also fibroblast like cell types at the beads - tissue interface were revealed with gradual degradation of implanted chitosan beads. From these results, it was suggested that flurbiprofen loaded chitosan beads can be effectively useful for biocompatible local delivery system in periodontal regeneration.

• YAKHAK HOEJI
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• v.59 no.2
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• pp.66-69
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• 2015

A concise synthesis of flurbiprofen, a member of the non-steroidal anti-inflammatory 2-arylpropionic acids, has been accomplished. The key feature of this synthesis involves successive palladium-catalyzed cross coupling reactions. In particular, a 2-arylacylate intermediate, which easily converted to the key 2-arylpropionic acid scaffold, was afforded by a versatile palladium-catalyzed cross coupling reaction between diazopropanate and bisphenylboronic acid. This synthetic procedure would facilitate synthesis of the flurbiprofen and anti-inflammatory 2-arylpropionic acid derivatives.

• Journal of Pharmaceutical Investigation
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• v.15 no.1
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• pp.15-21
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• 1985

The inclusion of ${\alpha}-cyclodextrin$ and ${\beta}-cyclodextrin$ with flurbiprofen in aqueous phase was investigated by UV absorption and circular dichroism spectroscopies. The inclusion complex in solid powder form were made by the freeze-drying and coprecipitation methods in molar ratio 1:1. The inclusion complex formation was confirmed by infrared absorption spectroscopy. The freeze-drying method was successful in obtaining the inclusion compounds compared with the coprecipitation method. The dissolution of solid flurbiprofen inclusion complex was examined in comparison with those of flurbiprofen alone. The inclusion complex obtained by freeze-drying method increased the dissolution rate.