Percutaneous absorption penetration enhancers

Bucks, D., and H.I. Maibach. 1999. Occlusion does not uniformly enhance penetration in vivo. In Percutaneous absorption Drugs, cosmetics, mechanisms, and methodology, 3rd ed., eds. R.L. Bro-naugh and H.I. Maibach. New York Marcel Dekker, chap. 4. 

Rastogi, S. K., and Singh, J. (2005), Effect of chemical penetration enhancer and iontophoresis on the in vitro percutaneous absorption enhancement of insulin through porcine epidermis, Pharm. Dev. Technol., 10(1), 97-104. 

Different light microscopy techniques, such as autoradiography and quantitative fluorescence microscopy (QFM), have been used to examine the influence of penetration enhancers on percutaneous absorption. 

Goodman, M. and Barry, B. W. Action of penetration enhancers on human stratum comeum as assessed by differential scanning calorimetry. In Percutaneous Absorption. Mechanisms, Methodology, Drug Delivery. R. L. Bronaugh and H. I. Maibach, ed. Dekker New York, 1989, pp. 567-593. 

Hadgraft, J., Penetration enhancers in percutaneous absorption. Pharmacy International 5 l0y.252-254, 1984. 

The studies just outlined indicate that neutron reflectometry has considerable potential for studying the mode of actions of skin penetration enhancers at a molecular level. Of particular interest in the field of percutaneous absorption... 

Some fatty acids, especially unsaturated fatty acids, are well-known skin penetration enhancers. The addition of PC to dermal dosage forms has been reported to increase percutaneous absorption. Lipid disperse systems (LDSs) containing polar lipids, such as PC and glycosylceramide, are also useful for increasing the percutaneous permeation of drug through rat abdominal skin in both in vitro and in vivo systems. 

Chattaraj, S.C. Walker, R.B. Penetration enhancer classification. In Percutaneous Absorption Enhancers Smith, E.W., Maibach, H.I., Eds. CRC Press Boca Raton Elorida, 1995 5-20. 

The use of ultrasound (US) to enhance percutaneous absorption (so-called sonophoresis or phonophoresis) has been studied over many years, and is the basis of US propagation and US effects on tissue, and the use of US in transdermal delivery have been reviewed in detail. The proposed mechanisms by which US enhances skin penetration include cavitation, thermal effects and mechanical perturbation of the SC that is, US acts on the barrier function of the membrane. ... 

The state of hydration of the stratum corneum, which is normally maintained at 10-15%, affects the rate of penetration of chemical substances. By increasing the state of hydration to 50%, the rate of permeation of some chemical substances through the epidermis can be increased up to 10-fold. ° Occlusion has been shown to enhance the pharmacological effect of topically applied hydrocortisone and fluocinolone acetonide " however, percutaneous absorption of drugs is not necessarily increased. The degree of occlusion-induced absorption enhancement appears to increase with increasing lipophilicity of drug substances. 

Gwak HS, Chun IK. Effect of vehicles and penetration enhancers on the in vitro percutaneous absorption of tenoxicam through hairless mouse skin. Int Pharm 2002 236(1-2) 57-64. 

Santoyo S, Arellano A, Ygartua P, Martin C. Penetration enhancer effects on the in vitro percutaneous absorption of piroxicam through rat skin. Int ] Pharm 1995 117(18) 219-224. 

Bucks D and Maibach HI. Occlusion does not Uniformly Enhance Penetration in vivo. Chapter 4. In Bronaugh RL and Maibach HI (eds.). Percutaneous Absorption Drugs—Cosmetics—Mechanisms—Methodology Edition). Marcel Dekker... 

Goodman M, Barry BW. Action of penetration enhancers as assessed by differential scanning calorimetry. In Bronaugh RL, Maibach HI, eds. Percutaneous Absorption. 2nd ed. New York Marcel Dekker, 1989 567-593. 

Baker, E. J., and J. Hadgraft. 1995. In vitro percutaneous absorption of arildone, a highly lipophilic drug, and the apparent no-effect of the penetration enhancer Azone in excised human skin. Pharm. Res. 

Newer vehicles include liposomes and microgel formulations. Liposomes are concentric spherical shells of phospholipids in an aqueous medium that may enhance percutaneous absorption. Variations in size, charge, and hpid content can influence liposome function substantially. Liposomes penetrate compromised epidermal barriers more efficiently. Microgels are polymers that may enhance solubilization of certain drugs, thereby enhancing penetration and diminishing irritancy. 

One in vivo Study on pigs (Qiao et al.. 1997) demonstrated that occlusion significantly enhanced pen-tachlorophcnol (PCP) absorption in a soil-based mixture from 29 to 85% of dose and changed the shape of the absorption profile in blood and plasma. The study also suggested that occlusion enhanced metabolism of PCP and resultantly the partitioning between plasma and red blood cells. Occlusion was kinctically linked to modification of cutaneous biotransformation of topical parathion (Qiao and Riviere, 1995). Occlusion enhanced cutaneous metabolism of parathion to paraoxon and to p-nitrophenol as well as the percutaneous absorption and penetration of both parathion and p-nitrophenol, This probably resulted in the... 

Barry. B. W, (1991). The LPP theory of skin penetration enhancement, In In Vitro Percutaneous Absorption Principles, Fundamentals, and Applications (R. L. Bronough and H. 1. Maibach, Eds.), pp. 165-185. CRC Press, Boca Raton, FL. 

The primary diffusion barrier of the SC is caused by the intercellular lipid domains located between the comeocytes. Investigation of the physical properties and molecular structure of these lipid domains is an important step in understanding the percutaneous absorption, which gives an insight into the effects of the penetration enhancers on SC lipids. X-ray and electron diffraction studies using small- and wide-angle are the most direct and powerful tools for acquiring this structural information for SC. 

Furthermore, attenuated total reflectance (ATR)-IR spectroscopy was useful for in vivo SC observations (Bommannan et al., 1990). It can be used to measure the water content in human SC (Potts et al., 1985 Edwardson et al., 1991). The method is used to measure the percutaneous absorption of drugs in addition to monitoring the effects of enhancers on the SC in vivo (Higo etal., 1993 Pirot etal., 1997). Electron spin resonance spectroscopy (ESR) can be used in vitro for studying the effects of penetration enhancer on SC (Rehfeld et al., 1990), and it is demonstrated to be nsefnl for evalnating the fluidity of SC (Alonso et al., 1995 Kawasaki et al., 1997 Mizushima et al., 2000). 

In vivo studies have shown the efficacy of fatty acids as potential skin penetration enhancers. Percutaneous absorption of dihydroergotamine was enhanced (208-fold)... 

Table 12.2 Summary of In Vitro Percutaneous Absorption of Drugs Using Fatty Acids as Penetration Enhancer...

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. 

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