• Biomolecules & Therapeutics
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• v.6 no.2
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• pp.213-218
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• 1998

A novel in situ-gelling and mucoadhesive acetaminophen liquid suppository was developed to improve the patient compliance of conventional solid suppository. In this study, acetaminophen liquid suppository, Likipe $n_{R}$, ［aminophen/Poloxamer 407/Poloxamer 188/so4ium alginate (5/15/19/0.6%)] with relation temperature at 30-36 "C and suitable gel strength and bioadhesive force, dissolution pattern similar to conventional solid type suppository, Suspe $n_{R}$, was developed. Furthermore, the bioequivalence of two acetaminophen products was evaluated in 16 normal male volunteers (age 22-27 yr, body weight 56-72 kg) following sidle rectal administration. Test product was Likipe $n_{R}$ suppository (Dong-Wha Pharm. Corp., Korea)and reference product was Suspe $n_{R}$204-212 suppository (Hanmi Pharm. Corp., Korea). Both products contain 125 mg of acetaminophen. Four Suppositories of the test and the reference product were administered to the volunteers, respectively, by randomized two period cross-over study (2$\times$2 Latin square method). The determination of acetaminophen was accomplished using HPLC. Average drug concentrations at each sampling time and pharmacokinetic parameters calculated were not significantly different between two products (p>0.05); the area under the curve to last sampling time (24 hr) (AU $Co_{-2}$4h/) (30.14$\pm$8.64 vs 27.98$\pm$ 6.53 $\mu$g .h/ml), maximum plasma concentration ( $C_{max}$) (3.29$\pm$0.87 vs 3.60$\pm$0.66 $\mu$g/ml) and time to maximum plasma concentration ( $T_{max}$) (2.91 $\pm$0.55 vs 2.69$\pm$0.60 h). The differences of mean AUCo $_{24h}$, C-a. and T-between the two products (7.18%, 9.58% and 7.53%, respectively) were less than 20%. The power (1-7) and treatment difference ($\Delta$) for AU $Co_{24h}$, $C_{max}$ and $T_{max}$ were more than 0.8 and less than 0.2, respectively at $\alpha$=0.1. The confidence limits for AU $Co_{24h}$, $C_{max}$ and $T_{max}$ (-0.81 ~13.55%, -1.56~ 17.60 and -3.81 ~18.87%, respectively) were less than $\pm$ 20% at $\alpha$=0.1. These results suggest that the bioavailability of Likipe $n_{R}$ suppository is not significantly different from that of Suspe $n_{R}$ suppsitory. Therefore, two products are bio-equivalent based on the current results.results.lts.sults.results.lts.

• Journal of the Korean Applied Science and Technology
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• v.31 no.3
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• pp.478-485
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• 2014

This study is to form the self assembly of cubic crystalline phase to penetrate into the skin epidermis. The various performance synthesized diglyceryl phytylacetate (DGPA) having hydroxyl group (-OH) and 4 methyl chains with phytyl group was carried out as an amphoteric lipid such as emulsifying power, self assembly. Emulsifying activity of DGPA was very stabilized on only 1% of small content, it could make a W/O emulsion containing high internal phase incorporated with water. Cubic liquid crystal structure with DGPA on three-phase diagram was formed, when mixed DGPA, dimethicone (2CS), and water. Through three-phase diagram forming the cubic liquid crystal area, hexagonal structure zone, and mixing water phase and hexagonal structure area, reversed micelle area were respectively certified. Its structure was proved by the SAXS (small angled x-ray scattering) analysis. As an application, formation of cubosome containing 10% of magnesium ascorbylphosphate and 5% of pyridoxine tris-hexyldecanoate was encapsulated. Occlusive effect of cubosome had above 1.7 times better than reversed micelle. From using poloxamer of dispersing agent, phase structure recovered from W/O emulsion to cubic liquid crystal phase when storage in $33^{\circ}C$ incubator. Therefore, our this study is expected to be as epidermal-dermal skin absorbers in skin care cosmetics and pharmaceuticals industries as raw materials to form a cubic crystal phase through a more in-depth research to DGPA having amphoteric lipid property.

• Biomolecules & Therapeutics
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• v.6 no.1
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• pp.45-49
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• 1998

The pharmacokinetic properties and antiinflammatory activity of 3% ketoprofen lotion (ID-lotion), formulated with poloxamer 407, were evaluated using rats. For the pharmacokinetic study, the lotion, at the dose of 4.5 mg/kg, was applied on the dorsal skin of rats and the drug concentration in plasma was determined using an HPLC method. As references, ketoprofen suspended in saline was administered orally, and E-lotion, which is a 3% ketoprofen lotion in the Japanese market was applied transdermally. Following the transdermal application of ID-lotion and E-lotion, $C_{max}$ were 316 $\pm$22.3 ng/ml and 163 $\pm$ 12.2 ng/ml, respectively, at the same Tma of 2 hours postdose, while $C_{max}$ and $T_{max}$ after oral administration of the drug were 1,030$\pm$89.1 ng/ml and 0.25 hours, respectively. Relative bioavailabilities of ID-lotion and I-lotion were 69.3% and 34.2%, respectively. The antiinflammatory activity of the two 3% ketoprofen lotions was evaluated with carrageeneninduced edema method after 50 mg of the lotions was applied on the paw of rats. ID-lotion showed 67.6% inhibition of the edema formation, while I-lotion showed 34.\\\\`r%. The calculated ED5o after transdermal application of ID-lotion was 2.5 mg/kg, while that after oral administration was 7.0 mg/kg. Based on these results, the relative equiponderal availability of ID-lotion was 296% compared to the oral administration of ketoprofen.n.n.n.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.6
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• pp.1528-1533
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• 2005

To evaluate the anti-hyperlipidemic effect of Brassica rapa L. and its major compound, $\beta$-sitosterol, the present study was undertaken, hypercholesterolemia was induced in rats with poloxamer-407, Triton WR-1339, 30% corn oil high cholesterol diet. The ethanol extract of Brassica rapa L. significantly decreased total cholesterol (TC), phospholipid, triglyceride at doses of 200 mg/kg, and $\beta$-sitosterol significantly exerted anti-hyperlipidemic activity at a dose of 15 mg/kg in rats with hyperlipidemia. Taken together, Brassica rapa L. and $\beta$-sitosterol can be useful agents for the prevention or treatment of hyperlipidemia.

• Journal of Pharmaceutical Investigation
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• v.28 no.4
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• pp.249-255
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• 1998

Solid Lipid Nanoparticle(SLN), one of the colloidal carrier systems, has many advantages such as good biocompatibility, low toxicity and stability. In this paper, the effects of drug lipophilicity and surfactant on the drug loading capacity, particle size and drug release profile were examined. SLNs were prepared by homogenization of melted lipid dispersed in an aqueous surfactant solution. Ketoprofen, ibuprofen and pranoprofen were used as model drugs and tweens and poloxamers were tested for the effect of surfactant. Mean particle size of prepared SLNs was ranged from 100 to 150nm. The drug loading capacity was improved with the most lipophilic drug and low concentration of surfactant. Particle size and polydispersity of SLNs were changed according to the used lipid and surfactant. The rates of drug release were controlled by the loading drug and surfactant concentration. SLN system with effective drug loading efficiency and proper particle size for the intravenous or oral formulation can be prepared by selecting optimum drug and surfactant.

• Journal of Pharmaceutical Investigation
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• v.39 no.4
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• pp.269-273
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• 2009

The objective of this investigation was to develop a gastro-retentive(GR) dosage form of gabapentin and was to evaluate of its dissolution characteristics. GR tablet consists of expandable core tablet matrix and semi-permeable membrane coating. Poloxamer 407 and sodium bicarbonate were used to prepare the core matrix. Polyvinly acetate dispersion (Kollicoat $SR30D^{(R)}$) and polyvinyl alcohol-polyethylene glycol copolymer ((Kollicoat $IR^{(R)}$)) were employed to form the semi-permeable membrane. The GR tablets significantly expanded up to fivefold in simulated gastrointestinal fluids with no apparent damage of the coating membrane over 12 hours. Also, the swelling rate was controllable with the amount of sodium bicarbonate. The drug release was observed to be substantially sustained based on coating level. The release rate of gabapentin from the GR tablet was gradually slowed down as the coasting amount was increased. The gabapentin GR tablet with 8% coating level showed a pseudo-zero order release kinetics over 12 hours. These results suggest that this swellable GR tablet system having semi-permeable membrane coating can be applicable for hydrophilic drug substances like gabapentin.

• Proceedings of the Membrane Society of Korea Conference
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• 1998.04a
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• pp.97-98
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• 1998

1. Introduction : Polypropylene(PP) membrane is widely used in the field of microfiltration and ultrafiltration. However, the hydrophobicity of PP causes the adsorption of hydrophobic and amphoteric solutes in the feed. Surface modification techniques of membrane through the treatment of hydrophilizing agents, coating of hydrophilic compounds, UV, plasma and high energy irradiation, etc. can have a great effect on propensities to prevent the protein from staining membranes. Among them, the modification to hydophilize membrane surface using UV is very simple and effective. Recently many studies for more effective surface modification have been conducted. Iwata et al. prepared membranes by grafting polyethylene glycol diacrylate macromer(PEGDA) onto polysulfone with plasma using a glow discharge reactor which prevent the oil from staining the membrane. The primary mechanism contributing to the membranes is preventing the oil from directly contacting the surface of the membrane as the PEGDA chains dissolved into emulsion. To evaluate their feasibility for use as a anti-fouling separation membrane, we prepared hydrophilic membranes by UV irradiation method and investigated their characteristics.

• Journal of Pharmaceutical Investigation
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• v.36 no.5
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• pp.305-308
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• 2006

Poloxamer-based hydrogel formulation for the topical delivery of ascorbic acid(AsA) was prepared and the effect of limonene on AsA skin permeation and localization was evaluated. In vitro rat skin permeation study, the AsA skin permeation of limonene-containing hydrogel was about 3 to 5 fold higher than control hydrogel. However the amount of permeated AsA was independent to the concentration of limonene. On the other hand the localized amount of AsA after 2 h increased proportion to the content of limonene. The increase in the ratio of localized AsA($Q_L$) to permeated AsA($Q_P$) was attributed to the limonene's ability of making polar pathway within stratum corneum by interacting on lipid domain of the skin and the AsA's hydration effect on the stratum corneum and effect on the protein domain of the skin.

• Journal of Pharmaceutical Investigation
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• v.34 no.3
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• pp.201-207
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• 2004

In order to develop an optimum formulation for iontophoretic flux of vitamine C 2-phosphate (VCP), we have prepared three different hydrogels containing VCP, using carbopol, HPMC and poloxamer, and iontophoretic flux through hairless mouse skin from these hydrogels was carried out. Drug stability in phosphate buffer (PBS) solution (pH 7.4) with and without current application was studied. The effect of various factors, such as drug concentration, current density, and current profile on skin flux was also investigated. Stability study indicated that VCP in PBS (pH 7.4) solution was stable under the experimental condition, irrespective of the presence of current. Cathodal delivery increased the flux markedly, whereas the anodal and passive flux was negligible. Thus, cathodal delivery was used in all experiments. Flux increased as the drug concentration (2.5, 5.0, 7.5%) and current density $(0.2,\;0.4,\;0.6\;mA/cm^2)$ increased. Pulsed application of the current showed lower flux than constant current application. The results obtained suggest that VCP can be delivered into the skin and the amount delivered can be controlled by varying hydrogel, current density, drug concentration and current application profile.

• Journal of Pharmaceutical Investigation
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• v.27 no.3
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• pp.199-205
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• 1997

In order to formulate biphenyl dimethyl dicarboxylate(DDB) aqueous solutions, the effects of various solubilizing agents such as cosolvents(PG, PEG 400, glycerin, ethanol), surfactants,$(poloxamer\;407,\;Cremophor^{\circledR}\; RH40,\;Solutol^{\circledR},\;Tween\;80,\;sodium\;lauryl\;sulfate)$, complexation agent$(CELDEX^{\circledR}\;CH-20)$ and others(urea, niacinamide, propylene carbonate, HPMC) on the solubility of DDB in water were evaluated. The solubility of DDB in water was about $0.21\;{\mu}g/ml\;at\;20^{\circ}C$, while its solubility in PEG 400 was 5,000 times higher than that in water. 60% PEG 400 aqueous solution was selected as an optimum solvent system, and surfactants or other solubilizing agents were added to prevent DDB from recrystalization. The addition of surfactants in water increased the solubility of DDB from 15- to 34-fold, however, $CELDEX^{\circledR}\;CH-20$ and other agents studied showed negligible effects on the solubility of DDB in water. The 60% PEG 400 aqueous solution containing 5% $Cremophor^{\circledR}$　RH40 was appeared as the formula of choice. It showed acceptable physical stability after stored for 7 days at $4^{\circ}C$.