• Journal of Pharmaceutical Investigation
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• 제33권2호
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• pp.141-144
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• 2003

The transdermal therapeutic system (TTS) of scopolamine has various advantages over its oral dosage forms. The ideal scopolamine TTS requires high skin permeation rate in short time after it is applied on the skin. In order to increase the initial skin permeation rate of scopolamine from TTS, various permeation enhancers were employed. Enhancers employed were fatty acids (oleic and linolenic acids), cyclic monoterpenes (menthol, camphor, cineole and limonene) and others (isopropyl myristate, sodium lauryl sulfate and glyceryl monostearate). The concentration of enhancers in the base were fixed to 5% (w/w). While fatty acids had little enhancing effect on the skin permeation of scopolamine, cyclic monoterpenes, isopropyl myristate and sodium lauryl sulfate resulted in $1.5{\sim}2.6-fold$ higher skin permeation rate of the drug compared to the control. However, lag time was not affected by enhancers studied.

• Journal of Pharmaceutical Investigation
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• 제28권3호
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• pp.141-149
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• 1998

In order to reduce systemic side effects following administration, flurbiprofen was formulated as O/W microemulsion consisting of the surfactant, oil phase and aqueous phase. Particle size distribution, apparent viscosity, solubility and skin permeation of flurbiprofen in various vehicles and microemulsion were evaluated. The domain of O/W microemulsion s phase diagram had difference between oil types and the area of O/W microemulsion was wide distributed by adding to PG and cosurfactant than that of water alone. As increasing 10, 15 and 20% of Brij 97 content and 1, 2.5, 5% of oil content, the solubility of flurbiprofen in O/W microemulsions and various vehicles was $400{\sim}1,000$ and $10{\sim}500$ times higher than that of control. Also, apparent viscosity of soybean oil microemulsions was higher than that of IPM microemulsions and that of vehicle were increased as increasing vehicle content. Since skin permeation of flurbiprofen decreased as increasing viscosity, in each vehicle, it was not affected 2% ${\beta}-CD$ and decreased as increasing PG content and to 2, 5 and 10% of $HP-{\beta}-CD$. In O/W microemulsion, 5% soybean oil. 20% Brij 97 and 75% water(A-1) with high viscosity showed low skin penetration.

• Journal of Pharmaceutical Investigation
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• 제32권4호
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• pp.259-265
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• 2002

Piroxicam is one of the NSAID, which is used in the systemic and topical treatment of a variety of inflammatory conditions. Conventionally, for topical use, the drug is formulated in gel. We designed an phonophoretic drug delivery system to investigate the piroxicam permeability and the influence of ultrasound application (continuous mode, pulsed mode), frequency (1.0 MHz, 3.0 MHz) and intensity $(1.0\;w/cm^2,\;1.5\;w/cm^2,\;2.0\;w/cm^2)$ with 0.5% piroxicam gel. Per cutaneous absorption studies were performed in vitro models to determine the rate of drug absorption via the skin. Permeation study using hairless mouse skin was performed at $37^{\circ}C$ using buffered saline (pH 7.4, 10% propylene glycol solution) as the receptor solution. Anti-inflammatory activity was determined using carrageenan-induced foot edema model in rat. A pronounced effect of ultrasound on the skin absorption of the piroxicam was observed at all ultrasound energy level studied. Ultrasound was carried out for 10 hr. The highest permeation was observed at intensity of $2.0\;w/cm^2$, frequency of 1.0 MHz and continuous output. The inclusion of phonophoresis was found to improve significantly the skin permeation in vitro and the anti-inflammatory activity in vivo.

• 약학회지
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• 제44권6호
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• pp.595-600
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• 2000

Transdermal delivery of ketorolac tromethamine, a potent non-narcotic analgesic, through human cadaver skin was investigated in vitro. A mixture of ethanol/water (40/60) containing 0, 1, 3, 5, and 8 (w/v)% L-menthol were used as a vehicle and penetration enhancer respectively. The permeation of ketorolac through human cadaver skin from saturated drug solution was evaluated at $37^{\circ}C$ with modified Franz diffusion cell. The in vitro skin flux and lag time were $1.23\;{\pm}\;0.11\;{\mu}g/cm^2{\cdot}hr$ and $5.56\;{\pm}\;0.34\;hr$, respectively. The cumulative amount of penetrated ketorolac containing L-menthol in ethanol/water (40/60) binary system was increased by the following order; 3%, 5%, 8%, 1%, 0%, and the lag time was decresed by the following order; 3%, 5%, 8%, 0%, 1%. The results suggested that a potential use of 3% L-methol is an effective penetration enhancer of ketorolac tromethamine through the human cadaver skin.

• 한국임상약학회지
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• 제6권2호
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• pp.24-27
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• 1996

In order to determine whether there was a clinically sufficient amount of drug remaining in used fentanyl patches, quantitative analysis of two different types of patches, each containing 2.5 mg (n=36) and 5 mg (n=20) was performed. After being used for approximately 72 hours by patients with cancer, each patch was put in the plastic bag and stored at $4^{\circ}C$ until analysis. Fentanyl remaining in patches was extracted with 50 ml methanol, diluted with water, and counted twice in a $\gamma-Counter$ (expressed as CPM). Patches that originally contained 2.5 mg and 5 mg of fentanyl were shown to have $0.48{\sim}1.86\;mg\;(mean:\;1.03\;mg,\;41.16\%)\;and\;0.37{\sim}3.95\;mg\;(mean:\;2.37\;mg,\;47.33\%)$ after use, respectively. A wide interpatient variability was observed in the rate of fentanyl release from patches although the application period was standardized to 72 hours. Since a significant amount of drug remained in the discarded patches, it is highly recommended that patients dispose used ones under supervision to prevent abuse or misuse of the narcotic drug.

• Biomolecules & Therapeutics
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• 제9권4호
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• pp.298-306
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• 2001

To develop a novel transdermal delivery system of loxoprofen (LP), a potent antiinflammatory and analgesic agent, the effects of vehicle composition and drug loading dose on the skin permeation property were investigated. And in vivo skin absorption property studied by analysing the $C_{max}$ and AUC was investigated after applying the developed plaster systems on rabbit back skin. Addition of isopropyl myristate (IPM) and IPM-diethylene glycol monoethyl ether (DGME) cosolvent in the plaster showed higher permeation rates than those from propylene glycol laurate-DGME cosolvent systems. As the concentration of LP in the plaster increased from 0.56 mg/$\textrm{cm}^2$ to 1.19 mg/$\textrm{cm}^2$, the drug release and skin permeation rates increased linearly. At loading dose of 1.19 mg/$\textrm{cm}^2$, the flux reached 35.6 $\mu$g/$\textrm{cm}^2$/hr. New LP plasters showed a good adhesive property onto skin, and showed no crystal formation. The AU $C_{0-24hr}$ and $C_{max}$ after dermal application of LP plaster (60 mg/70 $\textrm{cm}^2$) were found to be 6951$\pm$230 ng.hr/ml and 400$\pm$44 ng/ml, respectively. And the plasma concentration maintained above 300 ng/ml up to 24 hr period. In the carrageenan-induced rat paw edema test, LP plaster showed similar inhibition rate with marketed ketoprofen (Ketoto $p^{R}$) plaster.aster.r.

• Journal of Pharmaceutical Investigation
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• 제31권4호
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• pp.273-279
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• 2001

The purpose of this study is to characterize the iontophoretic transport of growth hormone releasing peptides (GHRP-6) through hairless mouse skin from aqueous solution. The effect of various factors, such as pH, poloarity, current profile, current density, current duration, ionic strength, drug concentration, and enhancer application was studied to obtain basic knowledge on the transport. We have also studied the stability of GHRP-6 in solution with/without current. The donor chamber was filled with phosphate buffer solution containing GHRP-6 and the receptor chamber was filled with phosphate buffer solution (pH 7.4). Ag/AgCl electrode was used for their stability and reversibility. At a predetermined time interval, sampling was made and the concentration of drug was analysed using HPLC system. The results showed that, compared to passive flux, the total amount of drug transported increased markedly by the application of anodal current. Cathodal flux was similar to passive flux. Flux increased with the current density, the duration of current application and drug concentration. The effect of enhancers on the flux was studied using hydrophilic (5% N-methyl pyrrolidone) and hydrophobic (5% propylene glycol monolaurate, 5% oleic acid) enhancers. Application of enhancer also increased the flux.

• Journal of Pharmaceutical Investigation
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• 제27권2호
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• pp.139-143
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• 1997

Epidermal growth factor (EGF) is a mitogen which activate the proliferation of basal cells in skin, which implicate the wound healing in severe skin damage such as burn. To carry out the preclinical test for the pharmacological action of EGF, EGF in transdermal delivery system must be stable. Since EGF is a protein susceptible to proteolysis and unstable in aqueous solution, in vitro stabilization of EGF is prerequisite for the formulation. In this study, effect of additives on the stability of EGF is investigated in vitro. The stability of EGF in aqueous solution was enhanced with the various water-soluble polysaccharides such as HPMC, sorbitol, mannitol and dextrin. EGF was successfully extracted from the ointment with 5% HPMC solution, and EGF in aqueous solution and ointment was also successfully stabilized with 5% HPMC. The ointments prepared with different amount of EGF were applied on the damaged dorsal skin of rats for the determination of optimal concentration of EGF. The ointment with EGF $(10\;{\mu}g/g)$ showed good wound healing action on the damaged skin of rats.

• 대한기계학회논문집B
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• 제41권7호
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• pp.463-468
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• 2017

경피를 통한 약물 전달 방식에 있어, 본 연구에서 제안하고 있는 바늘 없는 주사기 시스템은 레이저와 마이크로젯 인젝터로 구성 되어 있다. 이때 마이크로젯 인젝터의 핵심 메커니즘은 레이저 유도버블이다. 동력원으로 Nd:YAG와 Er:YAG, 두 종류의 레이저가 사용되었다. 버블의 특성을 결정짓는 레이저 변수인 펄스폭, 파장 등이 본 연구에서 고려되었다. Nd:YAG 레이저의 경우에 펄스폭이 버블의 생존 시간보다 짧기 때문에 캐비테이션에 가까운 버블을 형성하는 반면 Er:YAG 레이저의 경우에 펄스폭이 상대적으로 길고 물에서의 흡수가 잘 되기 때문에 보일링 버블이 만들게 된다. 버블 및 마이크로젯의 자세한 움직임은 초고속 카메라를 통해 촬영되었다. 이와 같은 과정을 통하여 마이크로젯의 특성이 버블에 의해 결정되는 것을 본 연구를 통해 관찰되었다. 약물 전달 성능은 기니어피그 조직에 형광물질을 침투한 결과로 부터 분석하였다.

• Journal of Pharmaceutical Investigation
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• 제31권4호
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• pp.217-224
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• 2001

To develop a novel transdermal delivery system of loxoprofen (LP), a potent antiinflammatory and analgesic agent, the effects of various vehicles and penetration enhancers on the skin permeation of LP from solution formulations were investigated. The permeation rate of LP through excised guinea pig skin was measured using a side-by-side permeation system at $32^{\circ}C$. The solubilities of LP in various vehicles were determined by the equilibrium solubility method, and partition coefficients $(P_c)$ were determined. The solubility of LP increased in the rank order of water & isopropyl myristate (IPM) & glyceryl dicaprylate/dicaprate & propylene glycol dicaprylate/caprate & propylene glycol laurate (PGL) & polyethylene glycol 400 & diethylene glycol monoethyl ether (DGME) & ethanol. n-Octanol-water $P_c$ value was 15.5. Among pure vehicles tested, IPM and PGL showed highest fluxes of $89.9{\pm}5.0$ and $45.4{\pm}0.3\;{\mu}g/cm^2/hr$ from saturated solutions, respectively. However, it was not possible to demonstrate any correlation between the solubility of LP and its permeation rate, indicating the change in the barrier property of the skin and/or carrier mechanisms by vehicles tested. The addition of DGME to IPM or PGL markedly increased the solubility of LP, but the permeation rate did not decrease when the concentration of DGME in the cosolvent was increased upto 40%. The addition of linoleic acid (3%) in the cosolvent slightly increased the permeation rate, but others such as lauroyl sarcosine, fatty alcohols and fatty acids tested did not show enhancing effect. In conclusion, the DGME-IPM or DGME-PGL cosolvent system proved to be a good vehicle to enhance the skin permeation of LP.