• 폴리머
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• 제27권6호
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• pp.536-541
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• 2003

불포화 폴리(3-히드록시알칸오에이트) (UPHA)를 생합성하고 이 고분자 매트릭스 내에서의 약물방출 경향을 조사하였다. UPHA의 생합성에 사용된 균주는 Pseudomonas oleovorans (ATCC 29347)이고 탄소원은 10-undecenoic acid를 사용하였으며 산-염기조절방법 배취형태 발효법을 이용하여 미생물 배양을 행하였다. 생합성된 UPHA는 $^1$H- 및 $^{13}$C-NMR, FT-IR, GPC 및 DSC 등을 사용하여 물리 및 화학적 분석을 행하였다. 약물방출 실험은 확산셀을 이용하여 모델약물인 케토프로펜의 방출량을 HPLC를 이용하여 측정하였고 UPHA의 가교도, 패취두께, 경피투과 향상제 등의 영향에 대하여 조사하였다. UPHA의 가교도의 증가에 따라 약물방출 속도가 늦어지고 약물방출 속도가 일정해지는 경향을 나타내었다. 경피투과용 패취의 두께가 두꺼워질수록 약물방출 지속시간이 길어지고 경피투과 향상제인 프로필렌 글리콜의 함량 증가에 따라 방출 속도가 향상되는 경향을 나타내었다.

• 대한의용생체공학회:의공학회지
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• 제23권3호
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• pp.189-196
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• 2002

피부를 통한 약물 전달 방법은 국소 병변 부에 직접적으로 약물을 전달할 수 있는 장점을 가졌으나 피부의 가장 바깥 층인 각질층의 장벽기능으로 인해 약물 전달 능력에 제한이 있다. 본 연구에서는 산소 압력 방법과 초음파 방법을 결합하는 방법을 시도하여 약물 전달 능력의 향상 정도를 검증해 본다. 흡수 물질로는 수분을 사용하였고 수분의 흡수도를 측정하기 위해 피부 임피던스 방법을 선택하였다. 실험은 총 42명을 대상으로 각각 대조군(13명) 초음파군(13명), 산소 압력군(6명). 초음파와 산소압력 결합군(10명)으로 나누어서 시행하였다. 각 군마다 다른 약물 전달방법을 손등 부위에 적용하여 20분간 피부 임피던스 변화를 측정 한 값을 PC에 저장하였다. 수분을 적용한 대조군의 경우 피부 임피던스의 변화가 거의 일어나지 않고. 초음파를 적용한 군과 산소를 적용한 군은 수분을 적용한 군보다 25-30배정도 높은 수분 홉수를 보였으며. 초음파와 산소 압력을 결합한 방법은 수분을 적용한 군보다 70배정도 높은 수분 흡수를 보였다. 이러한 평균의 타이를 반복 측정된 분산방법(Repeated Measures Analysis of Variance)의 다변량 검증과 다중비교를 통해 변화량간의 차이를 검증하여 유의성을 확인하였다

• Journal of Pharmaceutical Investigation
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• 제40권1호
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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.

• Journal of Pharmaceutical Investigation
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• 제36권2호
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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.

• Journal of Pharmaceutical Investigation
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• 제40권2호
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• pp.79-84
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• 2010

Osteoporosis was traditionally defined by the occurrence of nontraumatic fractures, especially of the spine, in the setting of low bone mass. Bisphosphonates are an important group of therapeutic agents for the management of osteoporosis, as they inhibit bone resorption and increase bone density, thereby potentially decreasing fracture risk. Risedronate sodium is a bisphosphonate class used by oral formulation. In this study, risedronate was transdermally delivered by iontophoresis. Effects of polarity, pH, current density, and drug concentration were studied using a side-by-side diffusion cell including the hairless mice skin. In addition we studied effect of enhancers. The flux was evaluated by HPLC/UV system. The amount of transported drug under iontophoretic delivery was approximately 186 fold higher than that under passive delivery. Flux was proportional to the increase of drug concentration and current density. The flux was observed about 0.68mg/$cm^2$ when the amout of Propyleneglycol monolaurate (PGML) used 1% as enhancer. Results indicated that iontophoresis is an effective method for transdermal administration of risedronate sodium

• 한국가시화정보학회지
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• 제10권2호
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• pp.32-38
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• 2012

In recent years a unique drug delivery system named as the transdermal drug delivery system has been developed which can deliver drug particles to the human skin without using any external needle. The solid drug particles are accelerated by means of high speed gas flow through a shock tube imparting enough momentum so that particles can penetrate through the outer layer of the skin. Different systems have been tried and tested in order to make it more convenient for clinical use. One of them is the contoured shock tube system (CST). The contoured shock tube consists of a classical shock tube connected with a correctly expanded supersonic nozzle. A set of bursting membrane are placed upstream of the nozzle section which retains the drug particle as well as initiates the gas flow (act as a diaphragm in a shock tube). The key feature of the CST system is it can deliver particles with a controllable velocity and spatial distribution. The flow dynamics of the contoured shock tube is analyzed numerically using computational fluid dynamics (CFD). To validate the numerical approach pressure histories in different sections on the CST are compared with the experimental results. The key features of the flow field have been studied and analyzed in details. To investigate the performance of the CST system flow behavior through the shock tube under different operating conditions are also observed.

• Journal of Pharmaceutical Investigation
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• 제34권3호
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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.

• 한국분말재료학회지
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• 제25권6호
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• pp.459-465
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• 2018

Most commercially available detonation nanodiamonds (DNDs) require further processing to qualify for use in biomedical applications, as they often contain many impurities and exhibit poor dispersibility in aqueous media. In this work, DNDs are modified to improve purity and impart a high colloidal stability to the particles. The dispersive and adsorption properties of modified DNDs are evaluated in terms of the suitability of DNDs as carriers for non-steroidal anti-inflammatory drugs (NSAIDs) in transdermal delivery. The study of adsorption on strongly positively and strongly negatively charged DNDs showed their high loading capacity for NSAIDs, and a pronounced relationship between the drugs and the particles' charges. Experiments on long-term desorption carried out with DND/NSAID complexes indicate that the nanoparticles exert a sustained effect on the drug release process.

• Journal of Pharmaceutical Investigation
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• 제40권1호
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• pp.23-31
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• 2010

In our previous work on levodopa delivery at pH 2.5 using iontophoresis, we found that cathodal delivery showed higher permeation than anodal delivery and electroosmosis plays more dominant role than electrorepulsion. In this work, we studied the transdermal transport of levodopa at very low pH (pH=1.0) where all levodopa molecules are cations, and evaluated some factors which affect the transdermal transport. The transport study at pH 2.5 was also conducted for comparison. The contribution of electrorepulsion and electroosmosis on flux was also evaluated. Using stable aqueous solution, the effect of electrode polarity, current density, current type and drug concentration on transport through skin were studied and the results were compared. We also investigated the iontophoretic flux from hydroxypropyl cellulose (HPC) hydrogel containing levodopa. In vitro flux study was performed at $33^{\circ}C$, using side-by-side diffusion cell. Full thickness hairless mouse skin were used. Current densities applied were 0.2, 0.4 or $0.6\;mA/cm^2$. Contrary to the pH 2.5 result, anodal delivery showed higher flux, indicating that electrorepulsion is the dominant force for the transport, overcoming the electroosmotic flow which is acting against the direction of electrorepulsion. Cumulative amount of levodopa transported was increased as the current density or drug concentration was increased. When amount of current dose was constant, continuous current was more beneficial than pulsed current in promoting levodopa permeation. Similar transport results were obtained when hydrogel was used as the donor phase. These results indicate that iontophoretic delivery of zwitterion such as levodopa is much complicated than that can be expected from small ionic molecules. The results also indicate that, only at very low pH like pH 1.0, electrorepulsion can be the dominant force over the electroosmosis in the levodopa transport.

• 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.