• Journal of Pharmaceutical Investigation
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• v.30 no.4
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• pp.273-278
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• 2000

Several topical preparations containing lidocaine, a widely used local anesthetic agent, have been developed and marketed recently for the treatment of premature ejaculation. In this study, microemulsion(ME)-based hydrogels containing lidocaine were prepared by dispersing ME to hydrogel bases such as Carbopol, sod. alginate, and sod. carboxymethylcellulose. Lidocaine-containing ME was thermodynamically stable over 6 months and had a diameter ranging from 10 to 100 nm. In vitro skin penetration of lidocaine from ME-based hydrogels followed apparent zero-order kinetics. ME-based hydrogel showed higher drug penetration during fifteen minutes after application than alcoholic hydrogel, reference preparation. Tail flick test in rat was introduced to compare in vivo local anesthetic effects of different hydrogels, and the results showed that ME-based hydrogels are superior to other hydrogels. In optical microscopy, recrystallization of lidocaine was observed within 5 min after application of reference hydrogel, but there was no change in ME-based hydrogels even after 30 minnute. These results indicated that ME-based hydrogels had some advantages in skin penetration, anesthetic effect and physical stability compared with alcoholic hydrogels. Finally it is possible to conclude that ME-based hydrogels containing lidocaine is a good topical drug delivery system for the treatment of premature ejaculation.

• Journal of Pharmaceutical Investigation
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• v.23 no.3
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• pp.1-8
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• 1993

A simple and quick method based on the transient diffusion theory for predicting the steady state rate of penetration of a drug after transdermal drug administration was proposed. The amount of drug entering the stratum corneum was determined by 20 strippings with an adhesive tape. From the profile of the amount of drug as a function of the number of strippings, the quantity of drug on the surface of stratum corneum was extrapolated. Based on the amounts of drug entering the stratum corneum during two time intervals $(t_1\;and\;t_2)$ within 1 hour after the application, the diffusion and partition coefficient were determined. Once the diffusion coefficient of the drug in the stratum corneum and the partition coefficient (stratum corneum/vehicle) were determined from the present approach, the steady-state flux of penetration across the stratum corneum was calculated. The steady-state rates of penetration of ascorbic acid and estradiol across hairless mouse skin were evaluated from this approach and compared with those obtained from ill vitro penetration experiment using excised hairless mouse skin. The data confirmed that the proposed method can predict the steady-state rate of penetration of these drugs across the stratum corneum.

• YAKHAK HOEJI
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• v.40 no.2
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• pp.155-162
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• 1996

Hyperkeratinization is a dermatologic disorder, which is due to the increase of corneocyte cohesion force. Glycolic acid, an alpha hydroxy acid(AHA), has been used to breakdown the hyperkeratinization processes. However, it has a problem of skin irritation when applied topically, due to the strong acidity especially in high concentration. A molecular optimization of glycolic acid has been tried to reduce the skin irritation by the way of prodrug formation. Ethyl glycolate was synthesized by the esterification of glycolic acid with ethanol in acidic conditions in the presence of sulfuric acid, and examined under the spectroscopic trials, such as UV, IR, $^1H$-NMR, and GC-MS. The physicochemical and biopharmaceutical properties of the prodrug were also evaluated. Through the toxicological tests of both skin irritation and eye mucous irritation, it has been proved that ethyl glycolate was less irritant than glycolic acid, since the pH value of synthetic prodrug was higher than that of glycolic acid. In the penetration test through nude mouse skin by diffusion cell, ethyl glycolate was continuously hydrolyzed to glycolic acid, which was assayed form the receptor compartment. It was obtained that the penetrated amount of ethyl glycolate was five times higher than that of glycolic acid. These results suggest that ethyl glycolate might be a successful prodrug of glycolic acid to reduce the skin irritation and to increase the skin penetration as well.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.49 no.2
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• pp.127-139
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• 2023

In this study, minoxidil, which is well known as a pharmaceutical raw material, and diaminopyrimidine oxide (DAO), which is a cosmetic raw material, were used as active ingredients to evaluate the physical properties of niosomes and compare the skin penetrations of artificial skin. To prepare niosomes of the size of nanoparticles, a high pressure homogenization method was used, and physical properties were evaluated with a zetasizer. The particle size of the noisome including the active ingredient was measured to be 99 to 123 nm according to HLB, and the zeta potential was measured in the range of -60 to -81 mV. Through DSC (differential scanning colorimetry), it was confirmed that minoxidil, a crystalline component, was uniformly dissolved in an amorphous state in niosomes. In order to confirm and compare skin penetration, it was measured by the in vitro Franz diffusion cell method, and the niosome formulation showed 3.4 times higher penetration for minoxidil and 11.1 times higher penetration for DAO than the control gel formulation. In addition, when comparing the skin penetration of minoxidil niosome and DAO niosome, a similar trend was shown, and the penetration amount of DAO was relatively high. The shapes of the niosome formulations with different HLB values were observed using Cryo-TEM, and it was confirmed that vesicles were formed in all of them and that they were intermediate between SUV (small unilamella vesicle) and LUV (large unilamella vesicle). Through this study, minoxidil, an effective drug for hair loss, and DAO, a cosmetic raw material, can be effectively delivered to the skin by encapsulating them in a noisome formulation.

• YAKHAK HOEJI
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• v.45 no.5
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• pp.506-512
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• 2001

Ketoprofen (KP) was formulated as a transdermal patch using the percutaneous penetration enhancers sorbitan monmmleate(SMO), polyvinylpyrrolidone(PVP). The control patch without penetration enhancers showed a KP flux of 8.9$\pm$0.75$\mu\textrm{g}$/$\textrm{cm}^2$/h The flux was increased in proportion to the concentration of SMO added. Furthermore, lag times were decreased upon addition of SMO. Conversely; the skin flux of KP was decreased in proportion to the concentration of PVP added. Pharmacokinetic parameters including $C_{max}$, $T_{max}$, and AUC were increased when SMO was added. However, $C_{mas}$ significantly decreased by the addition of PVP. $T_{max}$ was not significantly different in 2%, 4%, and 8% PVP patches. Patches containing 4% PVP showed the highest AUC value (19.158$\mu\textrm{g}$.h/ml). We found that the effectiveness of the two percutaneous penetration enhancers for topical KP patches was similar, with the addition of appropriate amounts of HPC modifying both skin flux and lag time of KP in the patches. In conclusion, it is possible to manufacture KP patches exhibiting high AUC, high skin flux, and short lag time using percutaneous penetration enhancers of SMO and PVP.

• Proceedings of the Korean Society of Near Infrared Spectroscopy Conference
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• 2001.06a
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• pp.3101-3101
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• 2001

Near Infrared spectroscopy (NIR) used on human skin measurement was explored in the past decade. Many publications in different journals and magazines discussed the feasibility of the NIR technique for cosmetic product property studies. Based upon the results of pioneers, we have pursued some work of the NIR instrument coupled with a probe module for skin measurement in vivo and vitro. In part I of this paper, the specific Near Infrared spectroscopy instrument stability, human subject conditions and other parameters, which could affect the measurements reproducibility are discussed. Second derivative NIR spectra and Principle Components Analysis (PCA) are utilised for data interpretation. In part II of this paper, the relationship of human skin moisture and ageing, the gender information and finally, the discovery of penetration depth of NIR incident light on skin are reported. A theoretical penetration depth calculation equation is proposed. In part III, the study results of a couple of commercial skin care products effect will be described. The skin lotions were applied on human skin (in vivo) in order to exam the NIR feasibility to monitor the changes of moisture level. The results are consistently positive. From our primary study, it can conclude that the NIR is potentially a very powerful instrument for skin condition diagnostics, either for cosmetic and/or for medication purposes.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.47 no.2
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• pp.179-184
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• 2021

Stratum corneum known as a skin barrier, which maintains water in skin, is the outer layer of the skin. Natural moisturizing factors (NMF) are one of the constituents in stratum corneum and amino acids are the highest components among NMF. In this study, we designed stearic acid-based solid lipid nanoparticles (SLNs) for improved skin penetration of serine (Ser). Ser-capsulated SLN was manufactured by double-melting emulsification method. The mean particle size and zeta potential of SLNs were 256.30 ~ 416.93 nm and -17.60 ~ -35.27 mV, respectively. The higher the degree of hydrophobicity or hydrophilicity of emulsifiers, the smaller the particle size and the higher the stability and capsulation rate. In addition, skin penetration was conducted using SkinEthic^TM RHE which is one of the reconstructed human epidermis models. The results of Ser penetration demonstrated that all SLNs enhanced than serine solution. The amount of enhanced Ser penetration from SLNs were approximately 4.1 ~ 6.2 times higher than that from Ser solution. Therefore, Ser-loaded SLN might be a promising drug delivery system for moisturizing formulation in cosmeceutical.

• Journal of Pharmaceutical Investigation
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• v.31 no.2
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• pp.107-112
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• 2001

In order to reduce the systemic side effects and gastrointestinal irritation after its oral adminitration, ketoprofen was formulated as water-soluble packs. The effects of fatty acids and fatty alcohols on the penetration of ketoprofen through excised rat skins were evaluated. The role of stratum corneum as a protective barrier was also investigated. Fatty acids and fatty alcohols were generally effective in promoting ketoprofen penetration. The flux of ketoprofen through rat skin was maximized when oleic acid or lauryl alcohol was used as an enhancer. As the concentration of fatty acids and fatty alcohols varied from 0% to 10%, the amounts of ketoprofen penetrated were in direct proportion to that of fatty acids but those had no relationship with that of fatty alcohols. The penetration of ketoprofen through stripped skin was enhanced compared to normal skin irrespective of enhancer type, which indicated that the action site of enhancers would be stratum corneum.

• Biomolecules & Therapeutics
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• v.5 no.4
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• pp.357-363
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• 1997

The effects of formulation variables of topical lotion on the skin permeation of ketoprofen were evaluated using excised rat skins. The formulation variables were the amounts of poloxamer 407, drug and ethanol, and penetration enhancers. The Keshary-Chien diffusion cells were used for the diffusion study. The flux of ketoprofen linearly decreased as the concentration of poloxamer increased from 5% to 15% in the preparation, and linearly increased as the amount of drug increased. Penetration enhancers such as fatty acids and fatty alcohols showed markedly enhancing effects at the level of 5%. Among them, the highest flux was shown in linolenic acid. From these results, optimum formula containing 3% ketoprofen, 5% poloxamer 407, 40% ethanol and 5% linolenic acid having the flux of 537.6 $\mu$g/$\textrm{cm}^2$/hr were noted.

• Journal of the Korean Applied Science and Technology
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• v.24 no.4
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• pp.410-415
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• 2007

Functional cosmetics are intensively investigated for the effectiveness of skin whitening, anti-aging and slimming. For enhancing the effectiveness, active ingredients should be delivered into the cell in the dermis. The amounts of penetration of caffeine and $Arbutin^{(R)}$ were tested, in vitro, using Franz diffusion cell. Oil-in-water emulsions were used for the vehicles of the transport. For the measuring the amounts of active ingredients delivered into the dermal skin, tape stripping was done after finishing the penetration experiments. The amounts of delivered caffeine were $8.45{\pm}$ 1.26ug/ml before tape stripping and $3.45{\pm}$ 1.80ug/ml after tape stripping, however, the amounts of delivered $Arbutin^{(R)}$ was quite small to detect. From now on, proper vehicles are considered for enhancing the delivery of $Arbutin^{(R)}$ Hairless mouse skin was compared with pig skin as a transdermal delivery membrane. The aspects of delivery were similar, but the amount of delivered ingredients using pig skin was larger than that of using hairless mouse skin. Therefore, the pig skin would be considered as a membrane for drug delivery experiments.