Dong-Chool Kim

Enhanced Bioavailability of Soy Isoflavones by Complexation with β-Cyclodextrin in Rats

In order to improve the solubility and bioavailability of a soy isoflavone extract (IFE), inclusion complexes (IFE-β-CD) of the isoflavone extract with β-cyclodextrin (β-CD) were prepared and studied for their solubility and bioavailability. The aqueous solubility of the complexes of IFE with β-CD (2.0 mg/ml) was about 26 times that of IFE itself (0.076 mg/ml). The same dosages of IFE and IFE-β-CD were orally administered to SD rats (Sprague-Dawley) on an isoflavone glycoside (IFG) basis (daidzin, genistin and glycitin), and the plasma concentrations of daidzein, genistein and glycitein were measured over time to estimate the average AUC (area under the plasma concentration versus time curve) of the isoflavones. After the oral administration, the AUC values for daidzein, genistein and glycitein were 340, 11 and 28 μg·min/ml, respectively. In contrast, the respective AUC values after the administration of IFE-β-CD were 430, 20 and 48 μg·min/ml. The bioavailability of daidzein in IFE-β-CD was increased to 126% by the formation of inclusion complexes with β-CD, compared with that in IFE. Furthermore, the bioavailability of genistein and glycitein in IFE-β-CD formulation was significantly higher by up to 180% and 170%, respectively, compared with that of IFE p=0.008 and p=0.028, respectively). These results show that the absorption of IFE could be improved by the complexation of IFE with β-CD (IFE-β-CD).

Effect of microneedle on the pharmacokinetics of ketoprofen from its transdermal formulations

Non-invasive transdermal delivery using microneedle arrays was recently introduced to deliver a variety of large and hydrophilic compounds into the skin, including proteins and DNA. In this study, a microneedle array was applied to the delivery of a hydrophobic drug, ketoprofen, to determine if transdermal delivery in rats can be improved without the need for permeation enhancers. The ability of a microneedle to increase the skin permeability of ketoprofen was tested using the following procedure. A microneedle array was inserted into the lower back skin of a rat using a clip for 10 min. Subsequently, 24 mg/kg of a ketoprofen gel was loaded on the same site where the microneedle had been applied. Simultaneously, the microneedle was coated with 24 mg/kg of a ketoprofen gel, and inserted into the skin using a clip for 10 min. As a negative control experiment, only 24 mg/kg of the ketoprofen gel was applied to the shaved lower back of a rat. Blood samples were taken at the indicated times. The plasma concentration (Cp) was obtained as a function of time (t), and the pharmacokinetic parameters were calculated using the BE program. The group loaded with the microneedle coated with ketoprofen gel showed a 1.86-fold and 2.86-fold increase in the AUC and Cmax compared with the ketoprofen gel alone group. These results suggest that a microneedle can be an ideal tool for transdermal delivery products.

Improved Solubility and In Vitro Dissolution of Ibuprofen from Poloxamer Gel Using Eutectic Mixture with Menthol

To improve the solubility and in vitro dissolution of poorly water-soluble ibuprofen with poloxamer and menthol, the effects of menthol and poloxamer 188 on the aqueous solubility of ibuprofen were investigated. The dissolution study of ibuprofen delivered by poloxamer gels composed of poloxamer 188 and menthol were performed. In the absence of poloxamer, 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 eutectic mixture with 6 parts of menthol. In the presence of poloxamer 188, the solutions with the same ratio of menthol to ibuprofen showed abrupt increase in the solubility of ibuprofen. Furthermore, 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 poloxamer and that without menthol, respectively. The poloxamer gel with menthol/ibuprofen ratio of 1:9 and higher than 15% poloxamer 188 showed the maximum solubility of ibuprofen, 1.2 mg/ml. Menthol improved the dissolution rates of ibuprofen from poloxamer gels. Dissolution mechanism showed that the dissolution rate of ibuprofen from the poloxamer gels without menthol was independent of the time, but the drug might be dissolved from the poloxamer gels with menthol by Fickian diffusion. Thus, the poloxamer gels developed using eutectic mixture with menthol, which gave the improved solubility and dissolution of drug, are potential candidates for ibuprofen-loaded transdermal and rectal delivery system.

Development and Validation of HPLC Assay of a New Molecule, 6-methyl-3-phenethyl-3, 4-dihydro-1H-quinazoline-2-thione from Solid Lipid Nanoparticles and its Topical Formulations

Abstract A rapid and sensitive high performance liquid chromatography (HPLC) method has been developed and validated for the quantitative determination of a new molecule, 6-methyl-3-phenethyl-3,4-dihydro-1H-quinazoline-2-thione from solid lipid nanoparticles and its topical formulations according to the loading amount. This new molecule is going to be developed as skin whitening agents with topical formulations such as creams, ointments, and gels. The analyses were carried out on a Kromasil 60 CN column (10 µm, 250 mm × 4.6 mm) using a mobile phase composed of water-acetonitrile-diethylamine (600:400:4,v/v) adjusted to pH3.5 with phosphoric acid, following at a flow rate of 2 mL/min. Methyl benzoate was used as the internal standard (IS). The method offers excellent linearity with regression coefficient r2 > 0.998, good repeatability, reproducibility, and relatively short analysis time (20 min). The sample preparation was carried out by a simple extraction of a new molecule with mobile phase, subsequently sonicated for 10 min. The above HPLC conditions resolved the diluted new molecule, pharmaceutical excipients, and potential degradants within 20 min, with a new molecule eluting at about 12.7 min and IS at 4.2 min. System suitability parameters and validation parameters including method precision, accuracy, and linearity were setup. The relative standard deviations (RSD) of precisions in the solid lipid nanoparticles consisting of 0.25 g of a new molecule were satisfactory to 0.48%. The detects of quantification (LOD) and the limits of quantification (LOQ) for the new molecule in topical formulations, including 0.25 g of solid lipid nanoparticles, were 2.52 µg/mL and 5.37 µg/mL and the mean recovery value was 100.67% with a RSD less than 0.78%. The proposed procedures were successfully applied for the determination of the new molecule in solid lipid nanoparticles and its topical formulations and control during stability studies.

Effect of Ultrasound-Induced Hyperthermia on Cellular Uptake of P-gp Substrate and Non-P-gp Substrate in MDR Cells

A previous report recently demonstrated that ultrasound-induced hyperthermia (USHT:0.4 watts (W)/ at ) could increase cellular uptake of P-glycoprotein (P-gp) substrates in P-gp expressing cancer cell lines. Since P-gp plays a major role in limiting drug permeability in the multi-drug resistant (MDR) cells, studies were conducted to elucidate the mechanism of USHT on cellular accumulation of P-gp and non-P-gp substrate in MDR cells. To accomplish this aim, we studied the effects of USHT on the accumulation of P-gp substrate, R123 and non-P-gp substrate, antipyrine in MDR cells. We demonstrated that USHT increased permeability of hydrophobic molecules (R123 and -antipyrine). The enhanced permeability is reversible and size-dependent as USHT produces a much larger effect on cellular accumulation of -antipyrine (MW 188) than that of R123 (MW 380.8). These results suggest that USHT could affect MDR cells more sensitive than BBMECs. Also, the present results point to the potential use of USHT to increase cellular uptake of P-gp recognized substrates, mainly anti-cancer agents into cancer cells.

Pharmacokinetic Study of Decursinol Following Oral Administration in Rat

The objective of this study is to investigate the pharamacokinetic parameters of decursinol following oral administration in Sprague-Dawley rats. The plasma concentration of decursinol was determined by LC/MS with APCI positive mode. The m/z value of decursinol was observed at 247. Following oral administration of decursinol extract, the apparent clearance was , the absorption half life was , the elimination half life was , and the apparent volume of distribution was . The LC/MS method was successfully applied to the pharmacokinetic study of decursinol.