• Journal of Pharmaceutical Investigation
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• v.36 no.2
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• pp.97-102
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• 2006

The aim of this study was to investigate the feasibility and optimize permeability of slim patch type as a transdermal delivery system of caffein. Slim patch type was formulated and tested in modified Franz diffusion cell across cellulose membrane and hairless mouse skin in pH 5.8 phosphate buffer solution (PBS). The effect of $Pharmsolv^{\circledR}$ and drug concentration on permeation at four model, 1,2% $Pharmsolv^{\circledR}$ with $0.12\;mg/cm^2$ caffein and 0.12, $1.2\;mg/cm^2$ caffein with 2% $Pharmsolv^{\circledR}$ through hairless mouse skin was studied in vitro. The release of caffein from slim patch with various loading was fitted by the Higuchi's diffusion equation. The result showed that chemical $Pharmsolv^{\circledR}$ produced a large and significant increase of permeation. The effect of 2% $Pharmsolv^{\circledR}$ on permeation of caffein was greater about 10-fold greater than 1% $Pharmsolv^{\circledR}$ in first 60 minutes. The effect of drug concentration, however, was lower than that produced by chemical $Pharmsolv^{\circledR}$. Within the tested system, the most efficient combination for caffein slim patch type was $0.12\;mg/cm^2$ caffein with 2% $Pharmsolv^{\circledR},$ although $1.2\;mg/cm^2$ caffein with 2% $Pharmsolv^{\circledR}$ showed highest amounts permeation, because permeated percentages were significantly lower about $1/4{\sim}1/5$ times.

• Archives of Pharmacal Research
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• v.26 no.11
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• pp.892-897
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• 2003

Anticancer drugs have serious side effects arising from their poor malignant cells selectivity, Since insulin receptors highly express on the cytomembrane of some kind of tumor cells, using insulin as the vector was expected to reduce serious side effects of the drugs. The objective of this study was to evaluate the tumor targeting effect of the newly synthesized mitoxantrone-insulin conjugate (MIT-INS) with the drug loading of 11.68%. In vitro stability trials showed MIT-INS were stable in buffers with different pH (2-8) at $37^{\circ}C$ within 120 h (less than 3% of free MIT released), and were also stable in mouse plasma within 48 h (less than 1 % of free MIT released). In vivo study on tumor-bearing mice showed that, compared with MIT [75.92 $\mu g \cdot$ h/g of the area under the concentration-time curve (AUC) and 86.85 h of mean residence time (MRT)], the conjugates had better tumor-targeting efficiency with enhanced tumor AUC of 126.53 1l9 h/g and MTR of 151.95 h. The conjugate had much lower toxicity to most other tissues with targeting indexes ($TI^c$) no larger than 0.3 besides good tumor targeting efficiency with $TI^c$ of 1.67. The results suggest the feasibility to promote the curative effect in ca.ncer chemotherapy by using insulin as the vector of anti-cancer drugs.

• THE INTERNATIONAL COMMERCE & LAW REVIEW
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• v.13
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• pp.151-192
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• 2000

This study has been focused on the revisions and characteristics of the 7 non-maritime trade terms(EXW, FCA, CPT, CIP, DAF, DDU and DDP) in Incoterms 2000. Main characteristics are as follows: First, the use of different expressions intended to convey the same meaning has been avoided and the same expressions as appear CISG have been used. Second, the content of preamble in each trade terms has been shortened and definitedly. Third, if the parties are going to use variants of trade terms in Incotrems 2000, the meanings should be made clear by adding explicit wording in the contract of sale. Main revisions of the 7 trade terms are as belows: First, Incoterms 2000 has emphasized that in EXW, the seller delivers when he places the goods at the disposal of the buyer at the seller's premises or another named place(i.e. works, factory, warehouse, etc.) not cleared for export and not loaded on any collecting vehicle. Second, in FCA, delivery is completed; a) If delivery occurs at the seller's premises, the seller is responsible for loading. b) If delivery occurs at any other place, the seller is not responsible for unloading. Third, in CPT and CIP, all costs and charges relating to the goods whilst in transit until their arrival at the agreed place of destination, unloading costs and all duties, taxes and other charges as well as the costs of carrying out customs formalities payable upon import of the goods and for their transit through any country are linked with the content under the contract of carriage. Fourth, Incoterms 2000 has emphasized that in DAF, the seller delivers when the goods are placed at the disposal of the buyer on the arriving means of transport not unloaded, cleared for export, but not cleared for import at the named point and place at the frontier, but before the customs border of the adjoining country. Fifth, Incoterms 2000 has emphasized that in DDU, the seller delivers the goods to the buyer, not cleared for import(in DDP, cleared for import), and not unloaded from any arriving means of transport at the named place of destination. Sixth, if the parties do not intend to deliver the goods across the ship's rail, FCA, CPT and CIP instead of FOB, CFR and CIF should be used.

• Journal of Ginseng Research
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• v.42 no.4
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• pp.512-523
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• 2018

Background: 20(S)-Protopanaxadiol (20S-PPD) is a fully deglycosylated ginsenoside metabolite and has potent dermal antiaging activity. However, because of its low aqueous solubility and large molecular size, a suitable formulation strategy is required to improve its solubility and skin permeability, thereby enhancing its skin deposition. Thus, we optimized microemulsion (ME)-based hydrogel (MEH) formulations for the topical delivery of 20S-PPD. Methods: MEs and MEHs were formulated and evaluated for their particle size distribution, morphology, drug loading capacity, and stability. Then, the deposition profiles of the selected 20S-PPD-loaded MEH formulation were studied using a hairless mouse skin model and Strat-M membrane as an artificial skin model. Results: A Carbopol-based MEH system of 20S-PPD was successfully prepared with a mean droplet size of 110 nm and narrow size distribution. The formulation was stable for 56 d, and its viscosity was high enough for its topical application. It significantly enhanced the in vitro and in vivo skin deposition of 20S-PPD with no influence on its systemic absorption in hairless mice. Notably, it was found that the Strat-M membrane provided skin deposition data well correlated to those obtained from the in vitro and in vivo mouse skin studies on 20S-PPD (correlation coefficient $r^2=0.929-0.947$). Conclusion: The MEH formulation developed in this study could serve as an effective topical delivery system for poorly soluble ginsenosides and their deglycosylated metabolites, including 20S-PPD.

• Polymer(Korea)
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• v.36 no.6
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• pp.705-711
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• 2012

In this study, the elastic liposome consisted of egg phospholipids and edge activator ($Tego^{(R)}$ care 450) was prepared in order to supplement the defect of the conventional liposome. We prepared elastic liposome containing quercetin, known as natural antioxidant, and evaluated the vesicles size, elasticity, loading efficiency, stability, and in vitro skin permeation. The mean diameter of quercetin loaded elastic liposome formulations ranged between 208.2~303.4 nm and loading efficiency was observed 64.1~87.5%. The highest loading efficiency (87.5%) and deformability (28.3) were observed at the optimal ratio of 90 : 10 (egg phospholipids : $Tego^{(R)}$ care 450) among 0.1% quercetin loaded elastic liposome formulations. The elastic liposome formulation was selected for further transdermal permeation study. The elastic liposome ($129.9{\mu}g/cm^2$) exhibited more skin permeability than general liposome ($114.8{\mu}g/cm^2$) and 1,3-butylene glycol ($75.1{\mu}g/cm^2$) solution. This results suggest that the elastic liposome formulation using $Tego^{(R)}$ care 450 as a major edge activator could be useful for the delivery of active ingredient through the skin transdermal.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.32 no.3 s.58
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• pp.149-152
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• 2006

Natural safflower oleosomes are small ($1{\sim}3{\mu}m$) spherical shaped "reservoir", inside which the seed stores triglycerides for use as a future energy source. The surface of the oleosome is covered with a high molecular weight ($20{\sim}24$ KDa) oleosin protein which has been demonstrated to have emulsification properties. Traditionally, oleosomes from oil bearing seeds such as safflower were simply crushed to liberate the oil within. Our patented DermaSphere technology allows for the isolation of oleosomes in the intact state. Once isolated, these materials can be used in skin care formulations to deliver the emolliency, occlusivity, and anti-oxidant effects typically associated with safflower oil. However, because of the presence of the emulsifying oleosin protein covering the spherical oil body, oleosomes have self-emulsification property as well as can emulsify other oil phase in typical oil-in-water (O/W) emulsion. The oleosomes can literally serve as the entire non-active portion of the oil phase of a typical skin care product. Most importantly, natural oleosomes can be loaded with other oil-soluble active materials and can therefore be used as delivery systems for improved cosmetic efficacies. Oleosomes can be loaded with various actives, such as fragrances, vitamins, inset repellents, and UV chromophores. The loaded oleosomes can be utilized to either protect the active ingredients within the formulation itself or to allow for control release of those actives over time.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.38 no.2
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• pp.103-118
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• 2012

In this study, the cellular protective effect of isoquercitrin against $H_2O_2$ and rose bengal-indued HaCaT cell damage was investigated. The ethosome and elastic liposome for enhanced transdermal delivery were prepared. Particle size, loading efficiency and cumulative permeated amounts of them were evaluated. Isoquercitrin didn't show any characteristic cytotoxicity at 50 ${\mu}M$. When HaCaT cells were treated with 5 mM $H_2O_2$ and 25 ${\mu}M$ rose bengal, isoquercitrin protected the cells against the oxidative damage in a concentration dependent manner (6.25 ~ 50 ${\mu}M$). The size of 0.03 % isoquercitrin loaded ethosome was 222.85 nm and the loading efficiency was 82.26 %. The ethosome loaded with 0.03 % isoquercitrin was stable and maintained the constant particle size for 2 weeks after being prepared. The ethosome exhibited more enhanced skin permeability than general liposome and ethanol solution. The optimal ratio of lipid to surfactant of 0.1 % isoquercitrin loaded elastic liposomes was observed to be 89 : 5 through evaluating particle size (341.2 nm), deformability index (59.89), loading efficiency (54.3 %), and skin permeability (54.4 %).

• Proceedings of the Polymer Society of Korea Conference
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• 2006.10a
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• pp.263-263
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• 2006

Poly (ethylene glycol)(PEG) - Poly (${\varepsilon}-caprolactone(CL)$) - Poly (D,L lactide(LA) (PCLA-PEG-PCLA) was synthesized by ring-opening polymerization to form temperature sensitive hydrogel triblock copolymer. The triblock copolymer was acrylated by acryloyl chloride. ${\beta}-amino$ ester was used as a pH sensitive moiety, in this study ${\beta}$- amino ester obtained from 1,4-butandiol diacrylate, and 4, 4' trimethylene dipiperidine, it have pKb around 6.6. pH/temperature sensitive penta-block copolymer (PAE-PCL-PEG-PCL-PAE) was synthesized by addition polymerization from acrylated triblock copolymer, 1,4-butandiol diacrylate, and 4, 4' trimethylene dipiperidine. Their physicochemical properties of triblock and penta-block copolymers were characterized by $^1H-NMR$ spectroscopy and gel permeation spectroscopy. Sol-gel phase transition behavior of PAE-PCL-PEG-PCL-PAE block copolymers were investigated by remains stable method. Aqueous media of the penta-block copolymer (at 20 wt%) changed from a sol phase at pH 6.4 and $10^{\circ}C$ to a gel phase at pH 7.4 and $37^{\circ}C$. The sol-gel transition properties of these block copolymers are influenced by the hydrophobic/hydrophilic balance of the copolymers, block length, hydrophobicity, stereo-regularity of the hydrophobic of the block copolymer, and the ionization of the pH function groups in the copolymer depended on the changing of environmental pH, respectively. The degradation and the stabilization at pH 7.4 and $37^{\circ}C$, and the stabilization at pH 6.4 and $10^{\circ}C,\;5^{\circ}C,\;0^{\circ}C$, of the gel were determined. The results of toxicity experiment show that the penta block copolymer can be used for injection drug delivery system. The sol?gel transition of this block copolymer also study by in vitro test ($200{\mu}l$ aqueous solution at 20wt% polymer was injected to mouse). Insulin loading and releasing by in vitro test was investigated, the results showed that insulin can loading easily into polymer matrix and release time is around 14-16days. The PAE-PCL-PEG-PCL-PAE can be used as biomaterial for drug, protein, gene loading and delivery.

• Journal of Pharmaceutical Investigation
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• v.40 no.1
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• pp.33-38
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• 2010

Sibutramine is a serotonin-norepinephrine reuptake inhibitor indicated for the management of obesity in conjunction with a reduced calorie diet. The oral administration of sibutramine is followed by its dose-related side effects. In this study, sibutramine was formulated into drug in adhesive (DIA) patches in an attempt to overcome these problems. The effects of different formulation variables including pressure-sensitive adhesive (PSA), loading amount of drug, thickness of matrix and enhancer on the skin permeation of the drug were evaluated using excised hairless mouse skin. In the acrylic adhesive with carboxyl functional group, low release of sibutramine was observed due to the strong interaction between carboxyl group of adhesive and amine group of sibutramine. The acrylic adhesive without functional group provided good adhesion force and allowed high drug loading. Changing drug load as well as thickness of the matrix was found to alter permeation rate. $Crovol^{(R)}$ PK40 and $Crovol^{(R)}$ A40, were found to be effective enhancers for sibutramine. The optimized patch contained 20% sibutramine, and 5% $Crovol^{(R)}$ A40 as permeation enhancer, in $80\;{\mu}m$ thick Duro-$Tak^{(R)}$ 87-9301 matrix.

• Macromolecular Research
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• v.10 no.5
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• pp.246-252
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• 2002

In order to the development of the delivery device of long-acting local anesthetics for postoperative analgesia and control of chronic pain of cancer patient, fentnyl-loaded poly (L-lactide-co-glycolido) (PLGA, molecular weight, 5,000 g/mole; 50 : 50 mole ratio by lactide to glycolide) microspheres (FMS) were studied. FMS were prepared by an emulsion solvent-evaporation method. The influence of several preparation parameters such as initial drug loading, PLGA concentration, emulsifier concentration, oil phase volume, and fabrication temperature has been investigated on the fentanyl release profiles. Generally, the drug showed the biphasic release patterns, with an initial diffusion followed by a lag period before the onset of the degradation phase, but there was no lag time in our system. Fentanyl was slowly released from FMS over 10 days in vitro with a quasi-zero order property. The release rate increased with increasing drug loading as well as decreasing polymer concentration with relatively small initial burst effect. From the results, FMS may be a good formulation to deliver the anesthetic for the treatment of chronic pain.