• Archives of Pharmacal Research
• /
• v.27 no.11
• /
• pp.1177-1182
• /
• 2004

The effect of poly[2-methacryloyloxyethyl phosphorylcholine] (pMPC) on the skin permeation property was investigated by performing in vitro skin permeation study of a model drug, nicotinic acid (NA). Effect of pMPC polymer in donor solution on skin permeation rates was evaluated using side-by-side diffusion cells. Also, the structural alterations in the stratum corneum (SC), inter-lamellar bilayer (ILB) and dermis layers in pMPC-treated and -untreated skin sections were investigated with transmission electron microscopy (TEM). The permeation profile of NA without pMPC in donor solution showed biphasic mode: initial $1^{st} phase and 2^{nd}$ hydration phase. The sudden, more than 10-fold increase in flux from the initial steady state (43.5 $\mu g/cm^2$/hr) to the $2^{nd}$ hydration phase (457.3 $\mu g/cm^2$/hr) suggests the disruption of skin barrier function due to extensive hydration. The permeation profile of NA with 3% pMPC in the donor solution showed monophasic pattern: the steady state flux (10.9 $\mu g/cm^2$/hr) without abrupt increase of the flux. The degree of NA permeation rate decreased in a concentration-dependent manner of pMPC. TEM of skin equilibrated with water or 2% pMPC for 12 h showed that corneocytes are still cohesive and epidermis is tightly bound to dermis in 2% pMPC-treated skin, while wider separation between corneocytes and focal dilations in inter-cellular spaces were observed in water-treated skin. This result suggests that pMPC could protect the barrier property of the stratum corneum by preventing the disruption of ILB structure caused by extensive skin hydration during skin permeation study.

• Journal of Pharmaceutical Investigation
• /
• v.33 no.2
• /
• pp.141-144
• /
• 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 the Korean Applied Science and Technology
• /
• v.25 no.2
• /
• pp.123-129
• /
• 2008

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 Nicotinic acid N-oxide 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
• /
• v.32 no.4
• /
• pp.313-319
• /
• 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.

• Biomolecules & Therapeutics
• /
• v.19 no.1
• /
• pp.109-117
• /
• 2011

In this work, we have investigated the effect of polyoxyethylene alkyl ester nonionic surfactants on percutaneous permeation enhancement of a model drug, ketoprofen. We also investigated the mechanism involved in the enhancement using impedance and solubility measurement. Three groups of nonionic surfactants with different ethylene oxide content were studied. The permeation results showed that all surfactants enhanced the percutaneous absorption, irrespective of the molecular weight. The permeation results from PEG-45 monostearate (PEGMS45) were rather unexpected. Impedance and solubility results indicate that the mechanism involved in the enhancement of permeation by PEG-10 monooleate (PEGMO10) and PEGMS45 is rather different. The results from PEGMS45 suggest that it could be a potential candidate as a skin penetration enhancer with high molecular weight, which may poses less skin irritation and systemic side effect than the smaller surfactant molecules. Overall, this work provided some useful information on percutaneous transport enhancement and the mechanistic insights involved in skin permeation for these nonionic surfactants.

• Journal of Pharmaceutical Investigation
• /
• v.37 no.3
• /
• pp.149-158
• /
• 2007

To investigate the permeability of lidocaine, percutaneous absorption studies were performed using excised hairless mouse skin and the penetration of lidocaine via the skin was determined. To increase the skin permeation of lidocine, the effects of $Labrasol^{(R)}$, $Labrafil^{(R)}$, $Labrafac^{(R)}$ and $Transcutol^{(R)}$ were investigated. The skin permeation of lidocaine was increased when $Labrasol^{(R)}$ and $Transcutol^{(R)}$ were used as permeation enhancer. To evaluate the influence of ultrasound, various factors such as application modes (continuous mode and pulsed mode), frequency (1.0 and 3.0 MHz) and intensity (1.0, 1.5 and 2.0 w/$cm^2$) were investigated with lidocaine hydrogel. The pronounced effect of ultrasound on the skin permeation of lidocaine was observed at all ultrasound energy levels. The influence of frequency having an effect on skin permeation rate was higher in the case of using 1 MHz, 2.0 w/$cm^2$ and continuous treatment. As the intensity of ultrasound increased, the permeation of lidocaine was accelerated. The in vivo anesthetic effects were evaluated by two aspects as mechanical threshold and electrical threshold. Six healthy volunteers consented to the randomized, double-blind, and cross-over designed study in each group. In each subject, 3 groups were adapted such as K group (ultrasound with gel base only), L group (lidocaine gel) and B group (ultrasound with lidocaine gel). In conclusion, lidocaine was potent anesthetic which could be block pain threshold effectively. And ultrasound could accelerate the skin penetration of lidocaine. The phonophoretic delivery system could be a good candidate for lidocaine as a local anaesthetic to improve the skin permeation and in vivo anaesthetic effect.

• Journal of the Korean Applied Science and Technology
• /
• v.17 no.2
• /
• pp.126-131
• /
• 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
• /
• v.25 no.2
• /
• pp.125-128
• /
• 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.

• Biomolecules & Therapeutics
• /
• v.25 no.4
• /
• pp.434-440
• /
• 2017

S-methyl-$\small{L}$-methionine (SMM), also known as vitamin U, is commercially available as skin care cosmetic products for its wound healing and photoprotective effects. However, the low skin permeation expected of SMM due to its hydrophilic nature with a log P value of -3.3, has not been thoroughly addressed. The purpose of this study thus was to evaluate the effect of skin permeation enhancers on the skin permeation/deposition of SMM. Among the enhancers tested for the in vitro skin permeation and deposition of SMM, oleic acid showed the most significant enhancing effect. Moreover, the combination of oleic acid and ethanol further enhanced in vitro permeation and deposition of SMM through hairless mouse skin. Furthermore, the combination of oleic acid and ethanol significantly increased the in vivo deposition of SMM in the epidermis/dermis for 12 hr, which was high enough to exert a therapeutic effect. Therefore, based on the in vitro and in vivo studies, the combination of oleic acid and ethanol was shown to be effective in improving the topical skin delivery of SMM, which may be applied in the cosmetic production process for SMM.

• Journal of the Korean Applied Science and Technology
• /
• v.17 no.1
• /
• pp.43-48
• /
• 2000

Drug delivery system(DDS) applied to various fields, such as medicine, cosmetics, agriculture and necessities of life. Among these application fields, DDS is often used as the method of drug dosage into the epidermic skin. We investigated characters of transdermal therapeutic system(TTS) and the skin permeability of that with applying DDS. Chitosan was selected as material of TTS. We investigated the permeation of chitosan ointment containing drug in rat skin using horizontal membrane cell model. Permeation properties of materials were investigated for water-soluble drug such as riboflavin in vitro. We used glycerin, PEG 600 and oleic acid as enhancers. Since dermis has more content water(hydration) than the stratum corneum, skin permeation rate at steady state was highly influenced when glycerin was used in water-soluble drug. The permeation rate of content enhancer and drug was found to be faster than that of content water-soluble drug only. These results showed that skin permeation rate of drug across the composite was manly 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.