Stratum corneum system coefficients

Emollients are often added to cream formulations to modify either the characteristics of the pharmaceutical vehicle or the condition of the skin itself to promote penetration of the active ingredient to act either locally or systemically. The stratum corneum, being keratinized tissue, behaves as a semipermeable artificial membrane, and drug molecules can penetrate by passive diffusion. The rate of drug movement depends on the drug concentration in the vehicle, its aqueous solubility, and the oil/ water partition coefficient between the stratum corneum and the product s vehicle. Commonly used emollients include glycerin, mineral oil, petrolatum, isopropyl pal-mitate, and isopropyl myristate. 

For example, the permeability coefficients of intact stratum corneum for lipophilic compounds such as corticosterone are in the order of 2 x lO cm/sec in an aqueous system. The aqueous solubility of corticosterone is approximately 0.3mg/mL.f A simple calculation using Eqs. (1) and (2) show why only potent drug of a required dose less than 1 mg per day can utilize the transdermal route via passive delivery. Physical and chemical transdermal enhancers are required for most drugs. Table 1 provides a list of transdermal enhancement methods and companies involved in the development of technologies related to these methods. The readers are encouraged to view the company websites listed in the table, but caution must be taken because the information and claims provided in a company website are subjective and not peer-reviewed. 

Now consider a poorly penetrating dermally applied compound, or one that is applied for such a short time T that only a small fraction of the applied dose is absorbed. In this case, it is the concentration c of the material in the formulation (as well as other factors that determine the flux across the stratum corneum, such as the dermal penetration coefficient Kp - see below), rather than the total applied amount of material, that determines the amount absorbed both into and through the skin. In simplest terms, the total amount Q absorbed into the systemic circulation is given by the equation ... 

A schematic representation of the multicomponent structure of the skin that takes these multiple barri-ers/pathways into account is shown in Figure 2. When penetration through the stratum corneum (including the parallel polar pathways) and through the aqueous layers in series with the stratum corneum are taken into account and combined with clearance into the bloodstream, the overall dermal penetration coefficient fCp(cmh ) for such a (simplified) composite system is given (by analogy with electrical... 

At the other end of the spectrum, however, in transdermal systemic delivery, the molecular attributes required are rather different. In this case, compounds are required to partition into the relatively lipophilic stratum corneum, diffuse rapidly across the stratum corneum and partition easily into the more hydrophilic viable epidermis and dermis prior to vascular removal. The intrinsic requirements of compounds for transdermal delivery are, therefore, a medium polarity (a log octanol-water partition coefficient of 1-3), a low molecular volume and a lack of potential to bind to skin components (e.g., via hydrogen bonding). 

More complicated vehicles or penetrant delivery systems will require a separate input function to be added to the model. Because of the passive nature of the stratum corneum barrier (.3), we may relate k to the substrate s diffusion coefficient (D ) through this outermost skin layer. Hence, in turn, k can be shown to be penetrant molecular weight (M) dependent via the Stokes-Elnsteln relationship (4) ... 

Theoretically, an ideal corticoid should permeate the stratum corneum and reach an adequate concentration in the epidermis without crossing the dermis to reach the systemic circulation. This may be achieved by increasing the lipophilicity of the topically active steroids resulting in an alteration of the partition coefficient. 

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