In-Joon Oh

Enhanced efficacy by percutaneous absorption of piroxicam from the poloxamer gel in rats.

The pharmacokinetics and anti-inflammatory activity of piroxicam from the poloxamer 407 gel were determined to investigate percutaneous absorption of piroxicam from poloxamer gels in rats. The poloxamer 407 gel containing 1% piroxicam showed significant inhibition of carragenin-induced rat foot swelling when compared to the control group. The extent of inhibition of swelling (%) showed a linear relationship with the logarithm of piroxicam dose within approximately 0.4-3.2 mg/kg. The enhancing effect of polyoxyethylene-2-oleyl ether, non-ionic surfactant on the percutaneous absorption of piroxicam from poloxamer 407 gel was evaluated in rats. The piroxicam gel containing polyoxyethylene-2-oleyl ether increaesd the relative bioavailability approximately 1.8-fold compared with the gel without enhancer. Percutaneous administration of piroxicam gel containing polyoxyethylene-2-oleyl ether to rats showed a relatively constant, sustained blood concentration with minimal fluctuation.

Release of adriamycin from poly(γ-benzyl-l-glutamate)/poly(ethylene oxide) nanoparticles

Abstract Prolonged circulation of anticancer agent in blood is expected to decrease the host toxicity and enhance the anticancer activity. The purpose of this study is to develop and characterize the prolonged and sustained release formulation of anticancer agent using biodegradable poly(γ-benzyl- l -glutamate)/poly(ethylene oxide) (PBLG/PEO) polymer nanoparticles. PBLG/PEO polymer is a hydrophilic/hydrophobic block copolymer and forms a micelle-like structure in solution. Spherical nanoparticles incorporating adriamycin were prepared by a dialysis method. The fluorescence intensity of adriamycin in the nanoparticles was increased when sodium dodecylsulfate was added. It is one of the evidences of entrapment of adriamycin in the polymer nanoparticles. Only 20% of entrapped drug was released in 24 h at 37°C a and the release was dependent on the molecular weight of hydrophobic polymer. The endothermic peak of adriamycin at 197°C disappeared in the nanoparticles system, suggesting the inhibition of a crystallization of adriamycin by polymer adsorption during the precipitation process. The mean residence time of adriamycin from the nanoparticles was more than threefold that from a free adriamycin. These results suggest usefulness of PBLG/PEO nanoparticles as a sustained and prolonged release carrier for adriamycin.

Mucoadhesive and physicochemical characterization of carbopol-Poloxamer gels containing triamcinolone acetonide

The viscosity and bioadhesive property of Carbopol-Poloxamer gels containing triamcinolone acetonide to mucosa were tested according to various concentrations of Carbopol gels of various pH. The increase in Carbopol concentration caused increased viscosity and bioadhesiveness. The neutralization of pH in various concentrations of Carbopol gels showed the increased viscosity, showing the highest viscosity and highest bioadhesiveness when neutralized to pH 6. A relationship between the viscosity and bioadhesive strength was shown from the neutralized Carbopol gels. The physicochemical interactions between triamcinolone acetonide and polymers were investigated by X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectrophotometry. According to FTIR and XRD studies, the drug did not show any evidence of an interaction with the polymers used and was present in an unchanged state.

Enhanced dissolution of furosemide by coprecipitating or cogrinding with crospovidone

Abstract To increase the dissolution rate of furosemide, cogrinding or coprecipitating of furosemide with crospovidone was carried out. The 1:2 (w/w) ground mixture of furosemide with crospovidone was prepared by cogrinding in a ceramic ball mill and the coprecipitate was prepared by the solvent method using methanol. The dissolution test was carried at 37±0.5°C and 150 rpm in simulated gastric fluids (pH 1.2). The dissolution rate of furosemide was rapid and markedly enhanced by cogrinding or coprecipitating with crospovidone. The X-ray diffraction, IR, DTA and TGA studies showed the physicochemical modifications of the furosemide from the ground mixture or the coprecipitate. Furosemide alone or furosemide contained within a physical mixture was crystalline in nature, whereas furosemide in the ground mixture or the coprecipitate was not crystalline even when preserved at room temperature for 1 year. An interaction, in the ground mixture or in the coprecipitate, such as an association between the functional groups of furosemide and crospovidone may have occurred at the molecular level, changed the thermal property and increased the dissolution of furosemide. The cogrinding or coprecipitating techniques with crospovidone provide a promising way to increase the dissolution rate of poorly soluble drugs.

Spectroscopic characterization of ibuprofen/2-hydroxypropyl-β-cyclodextrin inclusion complex

Abstract Ibuprofen has been used widely as an anti-inflammatory and anti-pyretic agent. It is slightly soluble in water. Several investigators have conducted studies to improve the dissolution rate of ibuprofen using cyclodextrin complexation. In this study, the geometry and the structural features of the ibuprofen/hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complex were studied by NMR and fluorescence spectroscopy. The fluorescence intensity of ibuprofen increased as the concentration of HPβCD increased. Continuous variation plots by NMR study suggested that 1:1 stoichiometric complex was formed in solution. The spectral analysis of 1 H- and 13 C-NMR measurements showed that the signals of the aromatic protons of ibuprofen were shifted upfield, probably resulting from the interaction of HPβCD with aromatic ring of ibuprofen. We also postulated the optimized structure of ibuprofen/HPβCD inclusion complex through a molecular modeling program (SYBYL 6.4) and we found that the features of this postulated structure were in a good agreement with the 1 H- and 13 C-NMR spectra.

Drug release from the enzyme-degradable and pH-sensitive hydrogel composed of glycidyl methacrylate dextran and poly(acrylic acid)

Hydrogels composed of glycidyl methacrylate dextran (GMD) and poly(acrylic acid, PAA) were prepared by UV irradiation method for colon-specific drug delivery. GMD was synthesized by coupling of glycidyl methacrylate to dextran in the presence of 4-(N,N-dimethylamino)pyridine. GMD was photo-polymerized by ammonium peroxydisulfate as initiating system in phosphate-buffered solution (0.1 M, pH 7.4). And then, acrylic acid monomer was added and subsequently heat-polymerized by 2,2′-azobisisobutyronitrile as an initiator. The hydrogels exhibited high swelling ratio (about 20) at 37°C, and showed a pH-dependent swelling behavior. In addition, the swelling ratio of the hydrogel was remarkably enhanced to about 45 times in the presence of dextranase at pH 7.4. The swelling-deswelling behavior proceeded reversibly for the GMD/PAA hydrogels between pH 2 and pH 7.4. Release of 5-aminosalicylic acid from the GMD/PAA hydrogels was evaluated in simulated gastrointestinal pH fluids in the absence or presence of dextranase. We concluded that the hydrogels prepared could be used as a dual-sensitive drug carrier for sequential release in gastrointestinal tract.

Transdermal delivery of triprolidine using TPX polymer membrane

Triprolidine-containing matrix was fabricated with poly(4-methyl-1-pentene) (TPX) polymer to control the release of the drug. Effect of penetration enhancer and stripping of skin on the permeation of triprolidine through the excised mouse skin was studied. Penetrating enhancers showed the increased flux probably due to the enhancing effect on the skin barrier, the stratum corneum. Among enhancers used such as glycols, fatty acids and non-ionic surfactants, polyoxyethylene-2-oleyl ether showed the best enhancement. The permeability of triprolidine was markedly increased with stripping the mouse skin to remove the stratum corneum, which acts as a barrier of skin permeation. For the controlling delivery of triprolidine, the TPX matrix containing permeation enhancer could be developed.

Thermorheologic Properties of Aqueous Solutions and Gels of Poloxamer 407

AbstractA Theological study of poloxamer 407 aqueous solution of 10–25% (w/w) concentrations was carried out at temperatures ranging from 27°C to 45°C and at various shear rates. An exponential relationship was found between viscosity and temperature, with curve slopes dependant upon poloxamer concentration. The viscosity of 25% poloxamer 407 aqueous solution showed a Newtonian fluid at 4°C and linearly increased on increasing temperature. The viscosity of 25 % poloxamer 407 aqueous solution was sharply increased at about 12°C and maintained highly constant. During such a desolvation process, the closer approach of polymer chains, which gave rise to an increase in the number of interactions among the chains, gave an increase in the solution viscosity with temperature. The gelling concentration was examined using an interfacial tensiometer. The results showed that the first inflection point appeared at the 0.003% (w/w) concentration and the second point appeared at the 17.5% (w/w) concentration. It implied...

Preparation and characterization of cytarabine-loaded w/o/w multiple emulsions

Abstract Cytarabine-loaded w/o/w multiple emulsions were prepared using nonionic surfactants of the Tween and Span types, and characterized by studying the osmotic behavior. The effect of the sonication period on the entrapment efficiency, droplet size and emulsion stability was investigated. The entrapment efficiency was up to 79% and was not affected by the loading dose. The size of droplets decreased with increase in the second sonication time. It was found that the oil layer of multiple emulsion droplets including the hydrophobic fatty acid tails of surfactants behaves as a water-permeable membrane between two aqueous phases of w/o/w multiple emulsion. The combination of Tween 20/80 and Span 20/80 as a hydrophilic and lipophilic surfactant system produced the most stable multiple emulsion. The release study showed that the multiple emulsion containing cytarabine in the internal aqueous phase was stable, exhibiting a prolonged release pattern.

Fluorescence spectroscopy studies on micellization of poloxamer 407 solution

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 l1/I3 and I339/I333 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-pyrenecar-boxaldehyde, the blue shift of the λmax 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.