• Journal of Pharmaceutical Investigation
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• 제39권1호
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• pp.19-21
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• 2009

This study was performed to examine the possibility of increasing the level of furosemide permeation from the ethylene-vinyl acetate (EVA) matrix through the skin by incorporating various enhancers in the EVA matrix. The effects of the enhancers on the level of furosemide permeation through the skin were evaluated using Franz diffusion cells with intact excised rat skins. The enhancers examined were the fatty acids (saturated, unsaturated), the pyrrolidones, the propylene glycol derivatives, the glycerides and the non-ionic surfactants. Among the enhancers used, polyoxyethylene-2-oleyl ether (a non-ionic surfactant) showed the best enhancement. The polyoxyethylene 2-oleyl ether as a permeation enhancer could be used for development of furosemide-EVA transdermal matrix system.

• 한국항공우주학회지
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• 제36권6호
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• pp.587-593
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• 2008

본 연구의 목적은 신체 조직의 손상을 최소화할 수 있는 경피(transdermal) 및 국부적인(topical) 약물전달을 가능하게 하는 마이크로 입자가속시스템 개발에 있다. Ballistic 역학을 기반으로 하는 본 방법을 통하여 체순환을 위한 경피 및 국부적 약물 전달이 가능하다. 얇은 금속 포일의 한 쪽 면에 마이크로 입자들을 얹어놓고 뒷면에 레이저를 조사하면 충격파가 발생하고, 이 충격파는 포일을 통과하며 포일의 끝에서 금속-공기간의 acoustic impedance 차이로 expansion wave로 반사되어 포일이 반대 방향으로 변형을 일으키게 한다. 이 순간적인 변형으로 인해 포일에 붙어있던 마이크로 입자들이 가속되어 튕겨 나가게 된다. 입자들이 가속되는 속도가 굉장히 크기 때문에 이들은 신체 조직을 침투할 만한 충분한 운동량을 갖고 있다. 입자들의 침투 여부를 확인하기 위해 우리는 5${\mu}m$ 크기의 코발트 입자들을 연조직을 묘사하는 젤라틴에 가속시켰으며, 주목할 만한 침투 깊이를 얻으며 실험에 성공하였다.

• 폴리머
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• 제37권3호
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• pp.347-355
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• 2013

본 연구에서는 항산화제인 quercetin과 그 배당체인 rutin의 피부 흡수를 증진시키기 위한 전달체로 다공성 셀룰로오스 하이드로젤을 제조하였고 그 특성을 연구하였다. Quercetin과 rutin을 위한 최적의 하이드로젤을 가교제인 12% epichlorohydrin(ECH)과 2% 셀룰로오스를 반응용액으로 하여 만들었다. 플라보노이드 함유 하이드로젤의 방출 실험에서, quercetin의 방출은 $10{\sim}500{\mu}M$ 농도에서 확산 속도에 영향을 받았으나, rutin의 경우는 비교적 낮은 농도($10{\sim}50{\mu}M$)에서 하이드로젤의 침식에 의한 방출이 지배적이었다. 플라보노이드에 대한 하이드로젤의 포집효율과 방출량은 quercetin보다도 rutin에서 모두 크게 나타났다. 하지만, Franz diffusion cell을 이용한 피부 투과 실험에서 quercetin이 rutin보다 1.2배나 더 큰 피부 투과능을 나타냈다. 플라보노이드 함유 하이드로젤은 대조군인 20% 1,3-butylene glycol phosphate buffer에서보다도 더 큰 경피 투과능을 나타내었다. 이 결과들은 난용성 항산화제인 플라보노이드의 피부 흡수 증진 전달체로서 셀룰로오스 다공성 하이드로젤이 이용 가능성이 있음을 시사한다.

• KSBB Journal
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• 제25권6호
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• pp.497-506
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• 2010

Vaccine is a protective clinical measure capable of persuading immune system against infectious agents. Vaccine can be categorized as live attenuated and inactivated. Live attenuated vaccines activate immunity similar to natural infection by replicating living organisms whereas inactivated vaccines are either whole cell vaccines, eliciting immune response by killed organisms,or subunit vaccines, stimulating immunity by non-replicating sub cellular parts. The components of vaccine play a critical role in deciding the immune response mediated by the vaccine. The innate immune responds against the antigen component. Adjuvants represent an importantcomponent of vaccine for enhancing the immunogenicity of the antigens. Subunit vaccines with isolated fractions of killed and recombinant antigens are mostly co-administered with adjuvants. The delivery system of the vaccine is another essential component to ensurethat vaccine is delivered to the right target with right dosage form. Furthermore, vaccine delivery system ensures that the desired immune response is achieved by manipulating the optimal interaction of vaccine and adjuvantwith the immune cell. The aforementioned components along with routes of administration of vaccine are the key elements of a successful vaccination procedure. Vaccines can be administered either orally or by parenteral routes. Many groups had made remarkable efforts for the development of new vaccine and delivery system. The emergence of new vaccine delivery system may lead to pursue the immunization goals with better clinical practices.

• International Journal of Precision Engineering and Manufacturing
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• 제9권3호
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• pp.68-71
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• 2008

Transdermal and topical drug delivery with minimal tissue damage has been an area of vigorous research for a number of years. Our research team has initiated the development of an effective method for delivering drug particles across the skin (transdermal) for systemic circulation, and to localized (topical) areas. The device consists of a micro particle acceleration system based on laser ablation that can be integrated with endoscopic surgical techniques. A layer of micro particles is deposited on the surface of a thin metal foil. The rear side of the foil is irradiated with a laser beam, which generates a shockwave that travels through the foil. When the shockwave reaches the end of the foil, it is reflected as an expansion wave and causes instantaneous deformation of the foil in the opposite direction. Due to this sudden deformation, the microparticles are ejected from the foil at very high speeds, and therefore have sufficient momentum to penetrate soft body tissues. We have demonstrated this by successfully delivering cobalt particles $3\;{\mu}m$ in diameter into gelatin models that represent soft tissue with remarkable penetration depth.

• 대한임상독성학회지
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• 제11권1호
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• pp.49-52
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• 2013

Fentanyl, a synthetic, highly selective opioid ${\mu}$-receptor agonist, is 50 to 100 times more potent than morphine. The low molecular weight, high potency, great transdermal permeation rate and lipid solubility of fentanyl make it very suitable for transdermal administration. Durogesic is a novel matrix transdermal system providing continuous systemic delivery of fentanyl. In recently, there are many reports that misused or overused fentanyl transdermal patches result in severe intoxication of fentanyl. We present a case of fentanyl toxicity with misused durogesic transdermal patch and discuss the safe and appropriate application of the patches. In conclusion, fentanyl patches should be used in opioid tolerant patients and prescribed at the lowest possible dose and titrated upward as needed. All patients and their caregivers should be educated safe application of fentanyl patches and advised to avoid exposing the patches application site to direct external heat sources, such as heating pads, or electric blankets, heat lamps, sauna, hot tubs, and others. In addition, concomittant medications that affect fentanyl's metabolism should be avoided.

• Journal of Pharmaceutical Investigation
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• 제37권4호
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• pp.243-247
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• 2007

Retinoids have many important and diverse functions and particularly, have been widely used as anti-aging agent and for the treatment of acne and psoriasis in cosmetics. However, retinoids have low stability against the air, light, water, oxygen and heat, thus, to stabilize the retinoids in formulations is very critical procedure. In this study, cubic liquid crystalline phase of monoolein was applied to stabilize the retinylpalmitate (RP) and to enhance the transdermal permeation. Cubic liquid crystalline phase significantly enhanced the stability of RP. After 15 days, the content of RP in the cubic formulation was 94.7% while the content of RP in ethanol solution was below 0.5% at room temperature. Although BHT containing crystalline phase showed the slightly increased stability of RP, there were no significant differences in RP stability between with or without antioxidants (ascorbic acid, ${\alpha}$-tocopherol, BHT, BHA) at $40^{\circ}C$. The skin retention of RP in crystalline formulations was approximately $5.3{\sim}6.4$ times greater than that of o/w cream formulation. Incorporation of RP into cubic liquid crystalline phase of monoolein effectively stabilized the RP and worked as excellent topical vehicle for RP. Liquid crystalline phase is considered to be suitable formulation for RP for topical delivery system as a stabilizer and permeation enhancing agent.

• Archives of Pharmacal Research
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• 제28권9호
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• pp.1097-1102
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• 2005

An O/W microemulsion system was developed to enhance the skin permeability of ace-clofenac. Of the oils studied, Labrafil? M 1944 CS was chosen as the oil phase: of the microemulson, as it showed a good solubilizing capacity. Pseudo-ternary phase diagrams were constructed to obtain the concentration range of oil, surfactant, Cremophor ELP, and co-surfactant, ethanol, for micoemulsion formation. Eight different formulations with various values of oil of $6-30\%$, water of $0-80\%$, and the mixture of surfactant and co-surfactant (at the ratio of 2) of $14-70\%$. The in vitro transdermal permeability of aceclofenac from the microemulsions was evaluated using Franz diffusion cells mounted with rat skin. The level of aceclofenac permeated was analyzed by HPLC and the droplet size' of the microemulsions was characterized using a Zetasizer Nano-ZS. Terpenes were added to the microemulsions at a level of $5\%$, and their effects on the skin permeation of aceclofenac were investigated. The mean diameters of the microemulsions ranged between approximately $10\~100nm$, and the skin permeability of the aceclofenac incorporated into the microemulsion systems was 5-fold higher than that of the ethanol vehicle. Of the various terpenes added, limonene had the best enhancing ability. These results indicate that the microemulsion pystem studied is a promising tool for the percutaneous delivery of aceclofenac.

• Archives of Pharmacal Research
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• 제27권7호
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• pp.763-768
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• 2004

To investigate the feasibility of developing a new quercetin transdermal system, a preformulation study was carried out. Therefore, the effects of vehicles and pressure-sensitive adhesives (PSA) on the in vitro permeation of quercetin across dorsal hairless mouse skin were studied. Among vehicles used, propylene glycol monocaprylate (PGMC) and propylene glycol mono-laurate were found to have relatively high permeation flux from solution formulation (i.e., the permeation fluxes were 17.25$\pm$1.96 and 9.60$\pm$3.87 $\mu\textrm{g}$/$\textrm{cm}^2$/h, respectively). The release rate from PSA formulations followed a matrix-controlled diffusion model and was mainly affected by the amount of PSA and drug loaded. The overall permeation fluxes from PSA formulations were less than 0.30 $\mu\textrm{g}$/$\textrm{cm}^2$/h, which were significantly lower compared to those obtained from solution formulations. The lower permeation fluxes may be due to the decrease of solubility and diffusivity of quercetin in the PSA layer, considering the fact that the highest flux of 0.26 $\mu\textrm{g}$/$\textrm{cm}^2$/h was obtained with the addition of 0.2％ butylated hydroxyanisole in PGMC-diethyl-ene glycol monoethyl ether co-solvents (80-85 ： 15-20, v/v). Taken together, these observations indicate that improvement in the solubility and diffusivity of quercetin is necessary to realize fully the clinically applicable transdermal delivery system for the drug.

• Journal of Pharmaceutical Investigation
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• 제27권4호
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• pp.303-311
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• 1997

Proliposomal patch of clenbuterol, ${\beta}_2-agonist$ bronchodilator, was prepared and its feasibility as a novel transdermal drug delivery system was examined. Proliposomal granules containing clenbuterol was prepared by a standard method using sorbitol and lecithin with (Rx 2) or without cholesterol (Rx 1). The porous structure of sorbitol in the proliposomes was maintained allowing tree flowability of the granules. Following contact with water, the granules were converted probably to liposomes almost completely within several minutes. It indicates that proliposomes may be hydrated, when they are applied on the skin under occlusive condition in vivo, by the sweat to form liposomes. Clenbuterol release from Rx 1 and Rx 2 proliposomes to pH 7.4 isotonic phospate buffer (PBS) across cellulose membrane (mol. wt. cut-off of 12000-14000) was retarded significantly compared with that from the mixture of clenbuterol powder and blank proliposomes. Interestingly, proliposomes prepared with lecithin and cholesterol (i.e., Rx 2 proliposomes) showed much more retarded release of clenbuterol than proliposomes prepared only with lecithin (i.e.. Rx 1 proliposomes), indicating that clenbuterol release from proliposomes can be controlled by the addition of cholesterol to the proliposomes. Proliposomal patches were prepared using PVC film as an occlusive backing sheet, two sides adhesive tape (urethane, 1.45 mm thickness) as a reservoir for proliposome granules and Millipore MF-membrane (0.45 mm pore size) as a drug release-controlling membrane. Rx 1 or Rx 2 proliposomes containing 4.6 mg of clenbuterol were loaded into the reservoir of the patch. Clenbuterol release from the patches to pH 7.4 PBS was determined using USP paddle (50 rpm)-over-disc release method. Clenbuterol release from the proliposomal patches was much more retarded even than from a matrix type clenbuterol patch (Boehringer Ingelheim ltd). Being consistent with clenbuterol release from the proliposomal granules, the release from the patches was highly dependent on the presence of cholesterol in the proliposomes : Patches containing Rx 2 proliposomes showed several fold slower drug release than patches containing Rx 1 proliposomes. When the patch containing Rx 1 proliposomes was applied on to the back of a hair-removed rat, clenbuterol concentration in the rat blood was maintained during 6-72 hrs. Transdermal absorption of clenbuterol from the patch was accelerated when the patch was prehydrated with 50 ml of pH 7.4 PBS before topical application. Above results indicate that sustained transdermal delivery of clenbuterol is feasible using proliposomal patches if the cholesterol content and pore size of the release rate-controlling membrane of patches, for example, are appropriately controlled.