Chemical penetration enhancers glycols

Transdermal delivery is a case in point. The skin, particularly the stratum corneum presents a formidable barrier to diffusion. Materials used to enhance its permeability have ranged from simple solvents such as ethanol or propylene glycol to aromatic chemicals such as terpenoids. Such penetration enhancers appear to work by disrupting the lipid domains in the stratum... 

On the other hand, SEPA (2-n-nonyl-l,3-dioxolane) has been shown to be a more versatile penetration enhancer in terms of its ease of formulation, chemical stability and its ability to enhance the skin penetration of a wide variety of compounds of varying physicochemical characteristics. Permeants that have been evaluated include indomethacin, ibuprofen, minoxidil, acyclovir, caffeine, econazole, papaverine, progesterone and estradiol. The degree of skin penetration enhancement using SEPA is dependent on the physicochemical characteristics of the permeant. For example, following application of indomethacin in a simple ethanol-propylene glycol vehicle to human skin in vitro, cumulative absorption over 24 h amounted to 0.7 percent of the applied dose. The addition of 2 percent SEPA to the vehicle increased the 24 h absorption value to 23 percent of the applied dose (Marty et al. 1989). Furthermore, in comparative studies between SEPA and Azone, SEPA was shown to be a more effective human skin permeation enhancer for indomethacin (Figure 14.6, Marty et al. 1989). 

For a good therapeutic effect the choice of the active substance and the choice of the vehicle are important. Physical and chemical factors play an important role. The solubility of the active substance in the vehicle and the concentration, the size of the molecule of the active substance, the partition between vehicle and skin, the particle size (in case of suspensions) and the nature of the vehicle (aqueous or lipid) determine the penetration speed and depth. Hydrocortisone, for example, is more lipid soluble in the ester form (hydrocortisone acetate). The latter will penetrate into the skin faster and more complete. Hydrocarbons, such as soft and liquid paraffin, release lipophilic active substances only very slowly and substances formulated in these bases will penetrate only in limited amounts into the skin. Fatty oils (vegetable oils, triglycerides) are able to pass into the upper layers of the skin. Penetration enhancers (salicylic acid, dimethyl sulfoxide, propylene glycol, urea) increase the penetration of active substances into the skin. 

Lastly, Jakasa et al. [102] observed a threefold increase in the absorption of polyethylene glycols through skin eroded by 5 % SLS, as opposed to Ortiz et al. s decrease [101], seemingly attributable to a more severe barrier damage secondary to heightened SLS concentration. Nonetheless, enhancement factors for penetration extracted from these few studies with chemical damage are modest to none. 

Glycolic acid creams, cleansers, and exfoliating preparations are used to boost epidermal exfoliation, reduce stratum corneum thickness and augment the peel penetration, thus enhancing the uniformity of the light chemical peel. Pretreatment is also essential for combination medium-depth peels. 

---