• 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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• 제32권4호
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• pp.313-319
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• 2002

Rat skin permeation of various nonsteroidal antiinflammatory drugs (NSAIDs) was investigated in vitro using Franz diffusion cell at $37^{\circ}C$. The effect of various skin permeation enhancers was also observed as a preliminary study of developing transdermal delivery systems of NSAIDs. Lipophilicity of NSAIDs was determined from thε partition coefficient (log P) in 1-octanol/water and 1-octanol/IPB mutual-saturated solutions. The solubility was determined in water, isotonic phosphate buffer (IPB), and propylene glycol (PG) at $37^{\circ}C$. The rat skin permeation rate of acetaminophen, piroxicam, and aceclofenac was almost negligible, although they were saturated in PG. Addition of 1 % permeation enhancer increased the permeation rate of ketoprofen, ketorolac, and diclofenac. However, the skin permeation rate of ibuprofen did not increase with the addition of various enhancers. Among the permeation enhancers testεd, oleic acid was the most effective for various NSAIDs. Based on the daily dose, lipophilicity, and the skin permeation ratε achieved in this study, ketoprofen and ketorolac seem to be the most promising drug candidates for transdermal delivery systems, especially when formulated with unsaturated fatty acids, such as oleic acid.

• Journal of Pharmaceutical Investigation
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• 제25권3호spc1호
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• pp.53-59
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• 1995

Ethinylestradiol (EE)-containing matrix was fabricated with ethylene-vinyl acetate(EVA) copolymer to control the release of the drug, Effect of addition of PEG 400 as receptor solution, the stripping of skin and Azone pretreatment on skin on the permeation of EE through the excised mouse skin was also studied. The permeation rate of EE through the excised mouse skin was affected by the PEG 400 volume fraction. The Azone pretreatment on skin didn't affect on the steady state flux, however, the lag time was shortened. The permeation rate of EE through the stripped skin was much larger than that through the whole skin. It showed that the stratum corneum acts as a barrier of skin permeation. The fact that there is little difference in EE permeation between the intact skin and the stripped skin with EVA membrane shows the permeation of EE through the mouse skin is mainly controlled by the membrane.

• 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.

• 약학회지
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• 제29권5호
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• pp.234-245
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• 1985

To clarify the diffusional behavior of p-aminbenzoic acid esters in the presence of polyethylene glycol 400, cellulose membrane permeation rate, solubility and viscosity of p-aminobenzoic acid methyl ester, benzocaine and butamben were determined with PEG solutions of various concentrations. With an increase in PEG concentrations permeation rates from solutions; decreased due to an increase in viscosity of the solution. From suspensions, however, permeation rates increased due to an increase in solubility and when the initial drug concentration was constant, permeation rates were found to be greatest from the PEG-water system with the PEG concentration which transported from the solution to the suspension. Permeation rate of 4.0mg/ml p-aminobenzoic acid methyl ester was $26.51\mu$g/ml$\cdot$hr from 5g/100ml PEG solution, and that of 4.0mg/ml benzocaine was $13.17{\mu}g/ml{\cdot}hr$ from 15g/100ml PEG, solution, and that of 2.0mg/ml butamben was $3.8{\mu}g/ml{\cdot}hr$ from 10g/100ml PEG solution. Permeation rate was 7.0 fold in p-aminobenzoic acid methyl, ester and 3.5 fold in benzocaine compared to butamben.

• Journal of Pharmaceutical Investigation
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• 제31권2호
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• pp.95-100
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• 2001

Various alkyl ester prodrugs of diclofenac were synthesized in order to investigate the relationship between their skin permeation characteristics and physicochemical properties. Solubility in various vehicles was measured at room temperature. 1-Octanol/water partition coefficients (Log P) and capacity factors (k') were measured to determine the lipophilicity of the prodrugs. Stability of prodrugs in the skin extract and homogenate was also investigated before conducting the skin permeation studies. Increases in the Log P and capacity factor values were observed when alkyl esters of diclofenac were prepared. Since the aqueous solubility of the prodrugs was not high enough, they were saturated in propylene glycol (PG) for skin permeation studies. Prodrugs were rapidly metabolized to diclofenac, both in skin homogenate and in dermal extract of skin. The skin permeation rate of alkyl ester prodrugs was significantly higher than diclofenac with shorter lag time. Moreover, a parabolic relationship was observed between the permeation rate and the log P values of prodrugs, and the maximum flux was achieved at a log P value of around 4.0.

• 산업기술연구
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• 제20권A호
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• pp.179-184
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• 2000

The surface of porous alumina membrane was modified with silane coupling agent in order to enhance hydrophobicity. The contact angle of water to the surface-modified alumina membrane was greater than $90^{\circ}$. The surface-modified membrane was tested in vapor permeation for the concentration of aqueous ethanol. With the increase of ethanol concentration in the feed, permeation flux increased due to the greater affinity of ethanol with surface-modified alumina membrane than that of water. The experimental results showed that the permeation rate of surface-modified alumina membrane was 15~1000 times greater than that of polymer membranes.

• 한국응용과학기술학회지
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• 제17권2호
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• pp.126-131
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• 2000

Transdermal therapeutic system(TTS) is often used as the method of drug dosage into the epidermic skin. Natural polymer were selected as ointment material of TTS. We investigated the permeation of natural polymer ointment containing drug in rat skin using horizontal membrane cell model. Permeation properties of materials were investigated for water-soluble drug such as oxiniacic acid in vitro. These results showed that skin permeation rate of drug across the composite was mainly dependent on the property of ointment base and drug. Proper selection of the polymeric materials which resemble and enhance properties of the delivering drug was found to be important in controlling the skin permeation rate. This result suggests a possible use of natural polymer ointment base as TTS of antihyperlipoproteinemic agent.

• Journal of Pharmaceutical Investigation
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• 제28권3호
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• pp.165-169
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• 1998

The effect of various vehicles on the permeation of a model drug, ketoprofen in solution formulation was evaluated using a flow-through diffusion cell system at $37^{\circ}C$. To investigate the mechanism of permeation rate enhancement, the effects of pretreatment with various vehicles on the permeation of the drug were evaluated using 5 mg/ml solution and saturated solution. The order of permeation rate of ketoprofen across hairless mouse skin after pretreatment with various vehicles was similar to the case where the vehicles and the drug were coadministered except ethanol and oleic acid. The results indicate that the mechanism of enhancement can be direct action of the vehicles on the barrier property of the skin and/or carrier mechanism.

• Journal of Pharmaceutical Investigation
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• 제25권2호
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• pp.125-128
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• 1995

To increase the skin permeation rate of flurbiprofen, fatty alcohols were added in propylene glycol vehicle containing 1% flurbiprofen. Their enhancing effect on the skin permeation of flurbiprofen was evaluated using Keshary-Chien diffusion cells fitted with excised rat skins. Lauryl alcohol and oleyl alcohol increased the skin permeation rate of flurbiprofen 11.3 and 8.5 fold, respectively, compared to the control vehicle.