Penetration enhancer terpenes

Barry B, Williams A. Human skin penetration enhancement the synergy of propylene glycol with terpenes. Proc Int Symp Control Release Bioactive Mater 1989 16 33-34. 

Williams, A.C., and B.W. Barry. 1991. Terpenes and the lipid-protein-partitioning theory of skin penetration enhancers. Pharm Res 8 17. 

Vaddi, H.K., P.C. Ho, and S.Y. Chan. 2002. Terpenes in propylene glycol as skin-penetration enhancers Permeation and partition of haloperidol, Fourier transform infrared spectroscopy, and differential scanning calorimetry. J Pharm Sci 91 1639. 

Vaddi, H.K., et al. 2003. Oxide terpenes as human skin penetration enhancers of haloperidol from ethanol and propylene glycol and their modes of action on stratum corneum. Biol Pharm Bull 26 220. 

Cornwell, P.A., et al. 1996. Modes of action of terpene penetration enhancers in human skin differential scanning calorimetry, small-angle x-ray diffraction and enhancer uptake studies. Int J Pharm 127 9. 

The most extensively studied amphiphilic and lipophilic penetration enhancers are oleic acid, oleyl surfactants, terpenes, alcohols, azone, azone analogues [84— 86], and FFAs. 

Cyclic monoterpenes increase the penetration of hydrophilic and lipophilic drugs [125-129]. Cornwell et al. found remarkable penetration enhancement of 5-fluorouracil after pretreatment with the noncyclic terpenes nerolidol, famesol,... 

A. C. Williams and B. W. Barry, The enhancement index concept applied to terpene penetration enhancers for human skin and model lipophilic (oestradiol) and hy-drophylic (5-fluorouracil) drugs, Int. J. Pharm. 76 157-161 (1991). 

Yamane, M. A., Williams, A. C. and Barry, B. W. Effects of terpenes and oleic acid as skin penetration enhancers towards 5-fluorouracil as assessed with time permeation, partitioning and differential scanning calorimetry. International Journal of Pharmaceutics 776 237-251, 1995. 

Cornwell, R A. and Barry, B. W. (1993). The routes of penetration of ions and 5-fluorouracil across human skin and the mechanisms of action of terpene skin penetration enhancers. Int. J. Pharm. 94 189-194. 

Terpenes such as o-limonene have been used as penetration enhancers (also called sorption promoters or accelerants) for improving transdermal drug delivery and work by penetrating into skin to reversibly decrease the barrier resistance. 

Terpenes are widely used chemical penetration enhancers (Williams and Barry, 1991b Barry and Williams, 1993). Structural formulas of terpaies used as penetration enhancers are presented in Figure 12.6. Terpenes are of low cutaneous irritancy, provide excellent enhancement ability, and appear to be promising candidates for pharmaceutical formulations (El-Kattan etal., 2001 Gao and Singh, 1998 Zhao and Singh, 1999). Table 12.4 lists the in vitro percutaneous absorption enhancement of drugs using terpenes. 

Cineole Ascaridole Limonene Oxide Pinene Oxide Figure 12.6 Structural formulas of some terpenes used as penetration enhancers. 

Table 12.4 In VHro Percutaneous Absorption of Drugs Using Terpenes as a Skin Penetration Enhancer...

The penetration-enhancing activities of monoterpenes, sesquiterpenes, and diter-penes were evaluated. Terpenes with relatively high lipophilic index exhibited absorption-promoting effects however, extremely high Upophilicity led to lower enhancing activities (Takayama et al., 1991). It was suggested that the difference in percutaneous absorption enhancing efficiency of terpenes arose from the difference in their thermodynamic activities in the vehicle (Obata et al., 1993). 

In Vivo Efficacy and Dermal Toxicity of Terpenes Used as Penetration Enhancers... 

Barry, B.W. and Williams, A.C. (1993). Terpenes as skin penetration enhancers, in K.A. Walters and J. Hadgraft (eds.). Pharmaceutical Skin Penetration Enhancement, New York Dekker, pp. 95-111. ... 

Godwin, D.A. and Michniak, B.B. (1999). Influence of drug lipophilicity on terpenes as transdermal penetration enhancers. Drug Dev. Ind. Pharm., 25 905-915. 

Yamane, M.A., Williams, A.C., and Barry, B.W. (1995). Terpene penetration enhancers in propylene glycol/water co-solvent systems effectiveness and mechanism of action, J. Pharm. Pharmacol, 47 978-989. 

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