DMSO used as a Penetration Enhancer

The term penetration enhancer is applied to materials that have a direct effect on the permeability of the skin barrier. Some materials may act by a direct chemical insult on the skin while others may not have a specific barrier effect. The latter may affect the solubility and/or dispersibility of the medicament and/or its delivery system (the vehicle). A variety of organic solvents are known to enhance the percutaneous absorption of medicaments, but few have been studied as extensively as dimethylsulfoxide (DMSO). Soon after the publication of its synthesis and physical properties, particularly the ease with which it traversed biological membranes, its potential as a penetration enhancer was and is still being investigated.

The superiority of DMS0 to other solvents both in enhancing penetration and in favoring dermal retention was demonstrated in a study of the passage of 14C-labelled griseofulvin, dissolved: in DMS0, dimethylacetaroide, dimethylformarnide, alcohol or benzene, through human skin in vitro. The ratios of penetration of griseofulvin in the various solvents was 60,40, 7, 3, and 1, respectively. Even when a 50% solution of DMSO in water was used, the rate of penetration of 14C hydrocortisone was markedly enhanced. The retention of griseofulvin and hydrocortisone in the excised skin roughly parallels their rate of penetration.

In other in vitro and in vivo experiments, DMSO has been shown to enhance the percutaneous penetration of many drugs. DMS0 has also been shown to enhance the rate of penetration of water through the skin when the epidermis was treated for 30 minutes with 60%, 80% and 90% aqueous solutions of DMSO.

Many theories concerning the mechanism of action of penetrants have appeared in the literature. One attributes the penetrant effects of DMS0, dimethylformamide, and dimethylacetamide to their hygroscopic properties which increase the water content of the stratum corneum, thereby greatly increasing its permeability. Another attributes the effectiveness of penetration enhancers to their ability to lower the barrier properties of the stratum corneum by modifying its natural structure. Organic solvents like benzene, alcohol, and ether, which have been shown to enhance the penetration rate of both water-soluble and lipid-soluble substances, may act by removing the lipids from the stratum corneum. The mechamam involved is probably hole formation. However, the action of hydrogen-bonding solvents like DMS0, dimethylformamide, and dimethylacetamide is attributed to membrane expansion and uniform increase in media diffusivity.

Surfactants are also used as penetration enhancers. Evidence regarding the influence of detergents and surfactants on epidernael permeability suggests that the effect of surfactants in lowering the surface tension of water is not an important factor in enhancing penetration of the skin even though skin lipids may be removed when the surface tension of water is decreased.

The effect of surfactants as penetration enhancers has been attributed to their ability to bind protein, thereby altering the structure of the stratum corneum. The importance of protein denaturation by some surfactants in increasing skin permeability has also been reported in more recent studies.

Miscellaneous Factors

Several other factors may influence the percutaneous absorption of medicaments: the site of application, the length of time such application remains in contact with the skin, the amount of inunction used in applying the medicated application, and skin temperature. Drugs which penetrate the stratum corneum do so most readily where the outer keratic layer is thin.

Although the information above (taken from Remington's Pharmaceutical Sciences) discusses high strengths of DMSO to inhance penetration, many have found that concentrations as low as 2% topical DMSO will significantly improve penetration.

Very high grades of DMSO are virtually odor free. The only kind we use at Acology.

Acology Prescription Compounding Center (http://www.Rx4u.com)