Skin permeation enhancer

Catz, P. and Friend, D.R. Alkyl esters as skin permeation enhancers for indomethacin, Int. J. Pharm., 55(l) 17-23, 1989. 

The use of skin permeation enhancers in combination for synergistic effects has been studied in the transdermal literature (70). Such synergistic methods can be grouped in three categories (i) combination of two physical methods, e.g., ultrasound and iontophoresis (71-75) (ii) combination of a physical method with a chemical enhancer, e.g., use of ultrasound with sodium lauryl sulfate or isopropyl myristate (76-80) and (iii) combination of two chemicals, e.g., terpenes and propylene glycol (46,81-88). Numerous studies have been published on using combination of two physical methods or use of a physical method in conjunction with a chemical enhancer. Use of a physical method, by itself or in combination with another physical method, increases application cost for delivery purposes as mentioned before. In addition, there are unexplored safety and membrane recovery issues associated with these methods. A few reports have also been published on the use of a mixture of chemical enhancers for enhancing transdermal delivery. Typically, such studies use... 

The phase map shown in Figure IB represents the skin permeation enhancement activity of the formulations containing binary mixtures of lauryl sarcosinate and sorbitan monolaurate at different concentrations and compositions. The region of maximum activity lies in a very narrow range of compositions. For such a nonlinear activity-composition behavior, it is very important to probe the binary phase map at as fine a resolution as possible, thus increasing the experimentation volume. 

Fang J, et al. Capsaicin and nonivamide as novel skin permeation enhancers for indo-methacin. Eur J Pharm Sci 2001 12 195-203. 

Kaplun-Frischoff Y, Touitou E. Testosterone skin permeation enhancement by menthol through formation of eutectic with drug and interaction with skin lipids. J Pharm Sci 1997 86 1394-1399. 

Cevc G. Transfersomes, liposomes and other lipid suspensions on the skin permeation enhancement, vesicle penetration, and transdermal drug delivery. Crit Rev Ther Drug... 

Kanikkannan N, Singh M. Skin permeation enhancement effect and skin irritation of saturated fatty alcohols. Int J Pharm 2002 248 219-228. 

He N, et al. Mechanistic study of chemical skin permeation enhancers with different polar and lipophilic functional groups. J Pharm Sci 2004 93 1415-1430. 

Vavrova, K., et al. 2003. Synthetic ceramide analogues as skin permeation enhancers Structure-activity relationships. Bioorg Med Chem 24 5381. 

Warner, K.S., et al. 2003. Structure-activity relationship for chemical skin permeation enhancers Probing the chemical microenvironment of the site of action. J Pharm Sci 92 1305. 

C. K. Lee, T. Uchida, N. S. Kim, and S. Goto, Skin permeation enhancement of tegafur by ethanol/panasate 800 or ethanol/water binary vehicle and combined effect of fatty acids and fatty alcohols, J. Pharm. Sci. 82 1155-1159 (1993). 

A new generation of transdermal drug delivery (TDD) system was developed to contain one or more skin permeation enhancers in the surface adhesive coating layers. This TDD system has been found, experimentally, to release the enhancers to the surface of stratum corneum to modify the skin s barrier properties, prior to the controlled delivery of the active drug. The extent of enhancement in skin permeability appears to be dependent upon the chemical structure of drug to be delivered transdermally as well as the type and the concentration of enhancer used. The mechanism of skin permeation enhancement have been explored and are analyzed in this report. 

Development of Skin Permeation Enhancers-releasing TDD System... 

The skin permeability of drugs has been reportedly improved by treating the stratum corneum surface with an appropriate skin permeation enhancer. Representatives of potential skin permeation enhancers are listed in Chart I. 

This new type of transdermal drug delivery system is capable of releasing one or a combination of two or more skin permeation enhancers to the stratum corneum surface in order to modify the skin s barrier properties (10), prior to the controlled delivery... 

It is interesting to note that the enhancement of skin permeation of drugs by fatty acid is dependent upon the alkyl chain length (Figure 6). In addition, the esterification of the carboxylic acid group reduces the effectiveness of fatty acids in skin permeation enhancement. The type of enhancer used and its concentration in the adhesive coating also play an important role in the extent of skin permeation (Figure 7). 

Figure 6. Dependency of the enhancement factor for the skin permeation of progesterone on the alkyl chain length of saturated fatty acids with maximum enhancement at n=6, and the effect of esterification on skin permeation enhancement.

Figure 9. Permeation profiles of progesterone across a delipid-ized skin and the effect of various skin permeation enhancers. Keys Control device (C) and enhancer-releasing device (A-...

As the surface concentration of enhancer in the adhesive coating increased, the mechanism of skin permeation enhancement showed some changes as reflected in the relative contribution of fatty matrix and protein gel pathways (Table VII ). The behavior for azone and oleic acid at high concentration was observed to be identical to that at low concentration (compare the data in... 

Marongiu, B., Piras, A. and Porcedda, S. (2004) Cyclic monoterpene extract from cardamom oil as a skin permeation enhancer for indomethacin in vitro and in vivo studies. 1. journal of Agriculture and Food Chemistry 52(20), 6278-6282. 

Smith, E.W. and Maibach, H.I. (eds) (1995) Percutaneous penetration enhancers. CRC Press, Inc., Boca Raton. Walters, K.A. and Hadgraft, J. (eds) (1993) Pharmaceutical skin permeation enhancement. Marcel Dekker, Inc. New York. 

Aungst, B. J. Fatty acids as skin permeation enhancers. In Percutaneous Penetration Enhancers. E. W. Smith and H. I. Maibach, eds. CRC Press Boca Raton, 1995 pp. m-1%1. 

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