AccessMyLibrary provides FREE access to millions of articles from top publications available through your library.
Modification of Skin Permeation by Solvents
While we often speak of the application of various materials (such as drugs or cleansers) to the skin, it is understood that the active ingredients are not at full strength. Most often, they are contained in a preparation or device, or, as in the case of soap, diluted with water before application. The vehicle serves as a means of conveniently applying a compound and controlling its concentration. Whether intended or not, the vehicle also plays a major role in determining the rate of uptake and penetration through the skin.
That the activity of topically applied medicaments can be modified by vehicles has been known for some time. For example, in 1933 it was shown that the germicidal effects of phenol could be obtained when that compound was applied to the skin in a cream base, but not a fatty base. 
The purpose of studying the mechanism of solvent effects on skin permeation is to be able to predict the direction in which changing the solvent will later permeation without having to do the experiment each time. Even in the absence of a definitive understanding of solvent effects on a molecular level, it is possible to devise empirical rules that are useful formulation guides.
It has been known for many years that certain solvents, such as dimethylsulfoxide (DMSO), can break down the skin's resistance to transport. This solvent, and others that are equally damaging to the barrier are not currently used in the U.S., although at least one pharmaceutical product containing this solvent has reached the market in Europe. Consequently, the remainder of our discussion will focus on solvents more likely to be encountered in skin products and treatments.
The situation is complicated because solvents can act on several levels and simultaneously modify permeation in different ways. By dividing these effects into categories, we attempt to devise a scheme that aids understanding and makes it possible to categorize much of the data in the literature in a rational way.
For most substances in most vehicles, the stratum corneum represents the principal barrier to transport. This is another way of saying that passage through the stratum corneum is usually the slowest (or rate-limiting) step. However, in rare instances, the rate-limiting factor may be the vehicle rather than one of the skin layers. It is always useful to determine which of the steps in the sequence of transfers leading from the vehicle through the skin is the slowest; this is what determines the overall rate.
Modification of the permeation rate requires alteration of one or more of the parameters involved in the slow step. Formulation changes that influence only the other (fast) steps in the process will not have a noticeable effect. Having sounded this alert, we will concentrate on the usual situation, in which stratum corneum transport is rate-limiting, and this will be our assumption throughout the remainder or this article.
It is possible to divide solvent effects into three categories. In the first group we consider physico-chemical characteristics of the solvent such as surface tension and rheology. Rheology is particularly important if vehicle transport is rate-limiting, but when diffusion across the stratum corneum determines the permeation rate, differences in vehicle viscosity have no significant effect. Surface tension of the liquid is one of the major factors determining the degree of contact with the skin surface and, therefore, the effective area through which permeation occurs.
The second category involves the driving force or difference in chemical potential across the stratum corneum. This has …