Biomedical subjects

Hoo-Kyun Choi

Publications and source records attributed to Hoo-Kyun Choi.

At least 19 recordsLinked to original sources

PubMed2006

Improved absorption of meloxicam via salt formation with ethanolamines.

The present study aimed to investigate the effect of ethanolamine salt formation on the dissolution as well as in vivo pharmacokinetics of meloxicam. Three meloxicam-ethanolamine salts were prepared and their in vitro dissolution profiles were examined at pH 1.2 and 6.8. The pharmacokinetic profiles of meloxicam following an oral administration of meloxicam or its ethanolamine salts were also evaluated in rats. The dissolution rates of meloxicam and its ethanolamine salts were similarly slow at pH 1.2, however, at pH 6.8, ethanolamine salt formation significantly enhanced the dissolution rate of meloxicam. Meloxicam diethanolamine salt exhibited the highest dissolution rate at pH 6.8. The faster dissolution of meloxicam via ethanolamine salt formation at pH 6.8 appeared to be correlated well with more rapid absorption of meloxicam in rats. Tmax of meloxicam was significantly (p<0.05) shortened following an oral administration of ethanolamine salts. Furthermore, ethanolamine salts exhibited a trend toward the increase in AUC0-4 (initial exposure), while the overall exposure (AUC0-24) was similar between meloxicam and its salts. In conclusion, the ethanolamine salts of meloxicam, particularly diethanolamine salt of meloxicam, facilitated the rapid absorption of meloxicam while maintaining the prolonged exposure and may be used for the earlier onset of action for meloxicam.

Administration, Oral↗

PubMed2006

The effects of surfactants on the dissolution profiles of poorly water-soluble acidic drugs.

The effects of types of surfactants on the solubilization and dissolution of poorly soluble acidic drugs were compared to identify the most suitable surfactant for conducting an acidic drug dissolution test. Cetyltrimethylammonium bromide (CTAB) as a cationic surfactant, sodium lauryl sulfate (SLS) as an anionic surfactant, and polysorbate 80 as a non-ionic surfactant were used in the study. And, mefenamic acid, nimesulide, and ibuprofen were selected as model drugs. The dissolution rates of these acidic drugs were substantially enhanced in medium containing CTAB. Electrostatic interactions between acidic drugs and cationic surfactants were confirmed by measuring UV spectra of each drug. Solubility of drugs in various media and the partition coefficients of drugs into micelles were found to depend on drug characteristics. For acidic drugs, the ability of media containing a cationic surfactant to discriminate rates of dissolution of acidic drugs seemed to be greater than that of media containing other surfactant types.

Cetrimonium↗

PubMed2006

Preparation of a solid dispersion of felodipine using a solvent wetting method.

A straightforward solvent wetting method was used to prepare felodipine solid dispersions in the presence of various carriers. Dichloromethane is not needed when HPMC solid dispersions were produced using the solvent wetting method. The amount of ethanol used to prepare solid dispersions did not have a significant effect on the dissolution rate of felodipine. The results of X-ray diffraction and thermal analysis indicated that the drug was in the amorphous state when PVP, HPMC, and poloxamer were used as carriers. The dissolution rates of felodipine in PVP, HPMC, or poloxamer solid dispersions were much faster than those for the corresponding physical mixtures. However, dissolution profiles were found to depend on the carrier used; the dissolution rate of felodipine increased slowly for solid dispersions prepared using HPMC, whereas rapid initial dissolution rates were observed for solid dispersions prepared using PVP or poloxamer. Increases in dissolution rates were partly dependent on the ratios of felodipine to carrier. No significant changes in crystal form were observed by X-ray diffraction or thermal analysis, and no significant changes in dissolution rate were observed when sorbitol and mannitol were used as carriers.

Calcium Channel Blockers↗

PubMed2005

Enhanced bioavailability of piroxicam via salt formation with ethanolamines.

Piroxicam can be ionized as a zwitterion that has two pKa values (pKa1=1.86 and pKa2=5.46). Consequently, piroxicam has a low solubility in both polar and nonpolar media, and a low lipophilicity, which results in a low permeability. Three piroxicam-ethanolamine salts were prepared, which had a higher area under the curve (AUC) than piroxicam. There were minimal differences in the AUC among the salt forms. It was reported that the piroxicam triethanolamine salt had a lower permeability across the skin than piroxicam but it had a higher oral bioavailability. Piroxicam monoethanolamine showed the highest Cmax followed by piroxicam diethanolamine and piroxicam triethanolamine. The dissolution rates of piroxicam and its salts were similar at pH 1.2. Piroxicam monoethanolamine showed the highest dissolution rate at pH 6.8, which was followed by the piroxicam diethanolamine and piroxicam triethanolamine salts. The order of dissolution rate at pH 6.8 matched the order of Cmax or the AUC after oral administration.

Administration, Oral↗

PubMed2005

Preparation of mucoadhesive microspheres containing antimicrobial agents for eradication of H. pylori.

Mucoadhesive microspheres containing either amoxicillin or clarithromycin were prepared via the interpolymer complexation of poly(acrylic acid) (PAA) with poly(vinyl pyrrolidone) (PVP) and solvent diffusion method. The complexation between the PAA and PVP in an ethanol/water mixture was confirmed by the change in the transmittance of the solution as a function of repeating PAA and PVP unit ratio. The loading efficiency of clarithromycin in the complex microspheres was higher than that of amoxicillin due to the stronger interaction of clarithromycin with the PAA. The microspheres had a spherical shape with a smooth surface and the inside of the microspheres was completely filled. The dissolution rate of the complex microspheres was significantly slower than that of the PVP microspheres, particularly at pH 2.0. Amoxicillin and clarithromycin degraded significantly during the release study at pH 2.0. Therefore, their release rates were corrected using first order degradation rate constants. The amoxicillin release rates were similar regardless of the pH of the medium, while those of clarithromycin differed depending on the pH. The release mechanism of amoxicillin was mainly by a diffusion process and that of clarithromycin was via a dissolution process. The drug release rate from the complex microspheres was significantly lower than that from the PVP microspheres.

Adhesives↗

PubMed2005

Preparation of mucoadhesive chitosan-poly(acrylic acid) microspheres by interpolymer complexation and solvent evaporation method II.

A mucoadhesive microsphere was prepared by an interpolymer complexation and solvent evaporation method, using chitosan and poly(acrylic acid) (PAA), to prolong the gastric residence time of the delivery system. The Fourier transform infrared results showed that microspheres were formed by an electrostatic interaction between the carboxyl groups of the PAA and the amine groups of the chitosan. X-ray diffraction and differential scanning calorimetry analysis showed that the enrofloxacin in the chitosan-PAA microsphere was molecularly dispersed in an amorphous state. Scanning electron microscopy of the surface and the quantity of mucin attached to the microspheres indicated that chitosan-PAA microspheres had a higher affinity for mucin than those of chitosan alone. The swelling and dissolution of the chitosan-PAA microspheres were found to be dependent on the pH of the medium. The rate of enrofloxacin released from the chitosan-PAA microspheres was slower at higher pH; therefore, based on their mucoadhesive properties and morphology, the chitosan-PAA microspheres can be used as a mucoadhesive oral drug delivery system.

Acrylic Resins↗

PubMed2005

Preparation and characterization of solid lipid nanoparticles (SLN) made of cacao butter and curdlan.

Solid lipid nanoparticles (SLN) were prepared using cacao butter, as the lipid core, and curdlan, as the shell material. Tween 80 was used as a co-surfactant in order to prevent aggregation and gelling of the curdlan. Mannitol was used as a cryoprotectant in order to prevent aggregation during redispersion. No significant change in the size of the SLN was observed up to a lipid concentration of 1.0%, and the particle size ranged from 140 to 200 nm with a unimodal distribution. When an alternating pH between 7 and 11 was used to test the physical stability of an SLN solution, the change in the particle size remained within a narrow range up to a lipid concentration of 0.5%. Above 0.5%, the particles began to aggregate due to the insufficient amount of the coating material, curdlan and Tween 80. The critical aggregation concentration at pH 7.4 was found to be 6.95 x 10(-4) mg/ml. Pyrene was used as a fluorescence probe. As the temperature increased, pyrene was gradually released from the SLN. The loading efficiency was >75% when the verapamil to lipid ratios were 1:10 and 1:5 and decreased significantly as the ratio became 1:1. The release rate was significantly delayed when verapamil was loaded into the SLN.

Cacao↗

PubMed2004

Mucoadhesive microspheres prepared by interpolymer complexation and solvent diffusion method.

Mucoadhesive microspheres were prepared to increase gastric residence time using an interpolymer complexation of poly(acrylic acid) (PAA) with poly(vinyl pyrrolidone) (PVP) and a solvent diffusion method. The complexation between poly(acrylic acid) and poly(vinyl pyrrolidone) as a result of hydrogen bonding was confirmed by the shift in the carbonyl absorption bands of poly(acrylic acid) using FT-IR. A mixture of ethanol/water was used as the internal phase, corn oil was used as the external phase of emulsion, and span 80 was used as the surfactant. Spherical microspheres were prepared and the inside of the microspheres was completely filled. The optimum solvent ratio of the internal phase (ethanol/water) was 8/2 and 7/3, and the particle size increased as the content of water was increased. The mean particle size increased with the increase in polymer concentration. The adhesive force of microspheres was equivalent to that of Carbopol. The release rate of acetaminophen from the complex microspheres was slower than the PVP microspheres at pH 2.0 and 6.8.

Adhesives↗

PubMed2004

Enhanced bioavailability of paclitaxel after oral coadministration with flavone in rats.

The purpose of this study was to investigate the effect of flavone on the bioavailability of paclitaxel orally coadministered in rats. Paclitaxel (40 mg/kg) and flavone (2, 10, 20 mg/kg) were orally administered to rats orally. The plasma concentration of paclitaxel with flavone increased significantly (P < 0.01) compared to that of paclitaxel control. Area under the plasma concentration-time curve (AUC) of paclitaxel with the dose of 2-20 mg/kg flavone was significantly (P < 0.05 at 10 mg/kg, P < 0.01 at 20 mg/kg) higher than that of control. AUCs of paclitaxel were increased dose-dependently in the dose range of flavone. The absorption rate constant (Ka) of paclitaxel with the dose of 10-20 mg/kg flavone was significantly increased (P < 0.05 at 10 mg/kg, P < 0.01 at 20 mg/kg) compared to that of control. Peak concentration (Cmax) of paclitaxel with the dose of 10-20 mg/kg flavone were significantly increased (P < 0.05 at 10 mg/kg, P < 0.01 at 20 mg/kg) compared to that of control. Half-life (t(1/2)) of paclitaxel with the dose of 10-20 mg/kg flavone was significantly prolonged (P < 0.05 at 10 mg/kg, P < 0.01 at 20 mg/kg) compared to that of control. The relative bioavailability increased significantly by about 2.38- or 3.10-fold (P < 0.05 at 10 mg/kg, P < 0.01 at 20 mg/kg) compared to that of paclitaxel control. Based on these results, It might be considered that the bioavailability of paclitaxel coadministered with flavone was significantly enhanced by the both inhibition of cytochrome P-450 and the P-gp efflux pump in the intestinal mucosa. It could be possible to administer paclitaxel orally besides the established i.v. route.

Adjuvants, Pharmaceutic↗

PubMed2004

Molecular mechanisms of inhibitory activities of tanshinones on lipopolysaccharide-induced nitric oxide generation in RAW 264.7 cells.

The effects of four tanshinones isolated from Tanshen (the root of Salvia miltiorrhiza Bunge, Labiatae) were tested for their inhibition of nitric oxide production in macrophage cells, and the underlying molecular mechanisms studied. Of the four tanshinones used, 15, 16-dihydrotanshinone-I, tanshinone-IIA and cryptotanshinone, but not tanshinone I, demonstrated significant inhibition of the LPS-induced nitric oxide production in RAW 264.7 cells, with calculated IC50 values of 5, 8, and 1.5 microM, respectively. Tanshinones exerted inhibitory activities on the LPS-induced nitric oxide production only when applied concurrently with LPS, and tanshinone-IIA and cryptotanshinone were found to inhibit LPS-induced NF-kappaB mobilization and extracellular-regulated kinase (ERK) activation, respectively. These results suggest that tanshinones inhibit LPS-induced nitric oxide generation by interfering with the initial stage of LPS-induced expression of certain genes. NF-kappaB and ERK could be the molecular targets for tanshinones for the inhibition of LPS-induced nitric oxide production in macrophage cells.

Abietanes↗

PubMed2004

Preparation and characterization of enrofloxacin/carbopol complex in aqueous solution.

Since the bitter taste of enrofloxacin apparently limit the patient compliance in the oral formulations of the antibacterial agent, the masking of the taste is essential for the improvement of the therapeutic effectiveness. Therefore, this study was carried out to examine the feasibility of taste masking of enrofloxacin by the retardation of its dissolution rate using the formation of complex between the drug and Carbopol. The complexation between Carbopol and enrofloxacin was confirmed by turbidity, UV spectrophotometry, wide angle X-ray diffraction, and differential scanning calorimetry. The enrofloxacin content in the complexes was 34% (Carbo-enrofloxacin complex I) and 57% (Carbo-enrofloxacin complex II) depending on the preparation method. The dissolution rate of enrofloxacin from the complex increased as the pH was reduced. The dissolution rate of enrofloxacin from the Carbo-enrofloxacin complex I was significantly lower than that of the enrofloxacin powder. Therefore, these observations suggest that Carbo-enrofloxacin complex I can be used to mask the taste of enrofloxacin.

Acrylic Resins↗

PubMed2003

Direct and biochemical interaction between dopamine D3 receptor and elongation factor-1Bbetagamma.

Novel signaling components of dopamine D3 receptor (D3R) were searched using yeast two-hybrid system, and the gamma subunit of elongation Factor-1B (eEF1Bgamma) was found to interact with D3R. This interaction was observed specifically between eEF1Bgamma and D3R but not with D2R or D4R. Immunocytochemical studies showed that D3R and eEF1Bgamma form clusters on the plasma membrane and their co-localization was evident in these clusters. The beta subunit of eEF1B (eEF1Bbeta), which forms a tight complex with eEF1Bgamma, was phosphorylated on serine residues in response to the stimulation of D3R. Phosphorylation of eEF1Bbeta was insensitive to pertussis toxin or wortmannin, however, stimulation of cellular protein kinase C (PKC) directly phosphorylated eEF1Bbeta and depletion of PKC abolished D3R-mediated phosphorylation of eEF1Bbeta. These results suggest the involvement of PKC, but not Gi/o proteins or phosphatidylinositol 3-kinase, in D3R-mediated phosphorylation of eEF1Bbeta. Stimulation of D3R did not activate PKC, but the activation of PKC resulted in the phosphorylation of D3R. These results show that PKC has a permissive role for the D3R-mediated phosphorylation of eEF1Bbeta, and suggest that PKC could modulate the mutual interaction between two protein by phosphorylating both D3R and eEF1Bbeta. Therefore, the cellular PKC level would be important for the D3R-mediated modulation of eEF1B, and for their cellular regulations such as protein synthesis or cellular proliferation.

Cell Line↗

PubMed2003

Preparation of buccal patch composed of carbopol, poloxamer and hydroxypropyl methylcellulose.

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.

Acrylic Resins↗

PubMed2003

Permeation of ciclopirox across porcine hoof membrane: effect of pressure sensitive adhesives and vehicles.

The purpose of this study was to investigate the effects of various pressure sensitive adhesives (PSA) on the penetration of ciclopirox across porcine hoof membrane. In addition, the influence of various vehicles on the permeation of ciclopirox from a PSA matrix across porcine hoof membrane was evaluated using a plastic penetration chamber containing poloxamer gel at 32 degrees C. Ciclopirox in poloxamer gel was extracted, derivatized and analyzed by HPLC. Ciclopirox showed highest permeability from an acrylic adhesive with a hydroxyl functional group, and this was followed by styrene-isoprene-styrene, styrene-butadiene-styrene, silicone and polyisobutylene adhesives in order. In addition, N-methyl-2-pyrrolidone (NMP), polypropylene glycol 400 (PPG 400), dimethylsulfoxide (DMSO), Labrasol, mercaptoethanol and Transcutol showed excellent permeation enhancing effects in a styrene-isoprene-styrene adhesive. A porcine hoof membrane treated with NMP changed from the non-helical phase to the helical phase, and another treated with DMSO showed a S=O peak shift to lower wavelength.

Adhesives↗

PubMed2003

Effect of ethanolamine salts and enhancers on the percutaneous absorption of piroxicam from a pressure sensitive adhesive matrix.

The effects of salt formation on the percutaneous absorption of piroxicam through hairless mouse skin from a pressure sensitive adhesive (PSA) matrix were investigated. We also studied the effect of permeation enhancers on the skin permeation of piroxicam or piroxicam-ethanolamine (PX-EA) salts from an acrylic adhesive matrix. The order of the permeation rates of piroxicam and PX-EA salts from the PSA matrix was piroxicam-monoethanolamine salt (PX-MEA)>piroxicam-diethanolamine salt (PX-DEA)>piroxicam>piroxicam-triethanolamine salt (PX-TEA). The enhancer Crovol A40 provided the highest piroxicam and PX-MEA fluxes and Plurol oleque the highest PX-DEA and PX-TEA fluxes. The order of piroxicam and PX-EA salts permeabilities were different for saturated solutions in various enhancers and PSA matrix containing the same enhancer, especially when Crovol A40, Crovol PK40 or Plurol oleque were used as enhancers. No close relationship was found between the fluxes of piroxicam or PX-EA salts from saturated solutions and from PSA matrices containing the same enhancer. Maximum piroxicam flux was obtained when PX-MEA/PX-TEA (4:6, v/v) was incorporated into a PSA matrix containing Crovol PK40.

Adhesives↗

PubMed2003

Self-assembled nanoparticles of hydrophobically-modified polysaccharide bearing vitamin H as a targeted anti-cancer drug delivery system.

Vitamin H (biotin) was incorporated into a hydrophobically modified polysaccharide, pullulan acetate (PA), in order to improve the cancer-targeting activity and internalization of self-assembled nanoparticles. The biotinylated pullulan acetate (BPA) nanoparticles were prepared by a diafiltration method and the mean diameter was approximately 100 nm. Three samples of biotinylated pullulan acetate (BPA), comprising 7 (BPA 1), 20 (BPA 2), and 39 (BPA 3) vitamin H groups per 100 anhydroglucose units of PA, were synthesized. The critical aggregation concentrations (CAC) of the BPA nanoparticles in distilled water were 3.1 x 10(-3), 4.3 x 10(-3) and 6.8 x 10(-3) mg/ml for BPA 1, BPA 2, and BPA 3, respectively. Adriamycin (ADR) was loaded into the BPA nanoparticles as a model drug. The loading efficiencies and ADR content in the BPA nanoparticles decreased with increasing vitamin H content due to a lower hydrophobicity. The RITC-labeled BPA nanoparticles exhibited very strong adsorption to the HepG2 cells, while the RITC-labeled PA nanoparticles did not show any significant interaction. The degree of the interaction increased with increasing vitamin H content. Confocal laser microscopy also revealed that internalization of the BPA nanoparticles into the cancer cells depended on the vitamin H content.

Antineoplastic Agents↗

PubMed2002

Pharmacokinetic and pharmacodynamic evaluation of cyclosporin A O/W-emulsion in rats.

The pharmacokinetics and pharmacodynamics of the cyclosporin A (CSA) O/W-emulsion were studied after intravenous and oral administration to Sprague-Dawley rats. Two commercial products, CIPOL Inj. and Sandimmun Neoral, were used as the reference formulations. CSA concentration and lymphocyte populations in whole blood were measured by TDxFLx and Coulter STKS, respectively. The pharmacokinetic and pharmacodynamic parameters were obtained by fitting experimental data to two-compartment model and to indirect pharmacodynamic model, respectively, using WINNONLIN. The area under the concentration-time curve (AUC), terminal half-lives (T(1/2)), total clearance (CL(t)) and relative bioavailability (F) after intravenous administration of CSA O/W-emulsion were not significantly different from those of intravenous administration of CIPOL Inj. (P>0.05). In oral administration, AUC and C(max) of CSA O/W-emulsion were significantly decreased (P<0.05), while T(1/2), MRT, T(max) and F were not significantly different (P>0.05) from those of Sandimmun Neoral. However, the area between the baseline and effect curves (ABEC) and pharmacodynamic efficiency (EFF) of CSA O/W-emulsion were significantly greater than those of references regardless of routes of administration (P<0.05). The pharmacodynamic availability (F(PD)) of CSA O/W-emulsion was 1.79- and 2.13-fold higher than that of CIPOL Inj.and Sandimmun Neroal (P<0.05), respectively.

Administration, Oral↗

PubMed2002

Effect of additives on the crystallization and the permeation of ketoprofen from adhesive matrix.

The crystallization of drug in a matrix may significantly affect the efficacy and quality of the transdermal drug delivery system. Therefore, the control of drug crystallization is of particular interest in the development of efficient transdermal delivery systems. In this study, we investigated the effects of various additives on the crystallization of ketoprofen in polyisobutylene (PIB) adhesive matrix. The effects of various additives on the permeation of ketoprofen from PIB matrix across hairless mouse skin were also examined. Poly(vinyl pyrrolidone) (PVP) K-30 was found to be the most effective crystallization inhibitor. Also, Poloxamer, Tween 80 and Labrasol significantly inhibited the crystallization of ketoprofen in a PIB matrix. In case of Tween 80, Labrasol, and PVP K-30, the flux of ketoprofen decreased as the loading content of the additives increased. However, the addition of Tween 80, Labrasol, or PVP K-30 significantly reduced the decrease in the flux of ketoprofen within the PIB matrix during a storage time of 3 weeks.

Adhesives↗