Formulation for transfollicular drug administration: some recent advances.

The percutaneous administration of drug products is of current therapeutic interest, mainly with regard to reduction of hepatic metabolism and systemic toxicity, and delivery to specific sites. Hair follicles and sebaceous glands can be privileged pathways for some molecules or formulations, which enter faster into these shunts than they do through the stratum corneum. The aim of this paper is to outline some examples of recent formulation methodologies that allow administration of a drug product through the follicular pathway (1) when the common, localized diseases of the pilosebaceous unit could benefit from specific delivery; and (2) to shunt the stratum corneum barrier.

Follicles play an important role in percutaneous absorption.

The relative importance of stratum corneum and follicles in percutaneous absorption is not fully understood. In order to quantitatively investigate the importance of the transappendageal route, we have previously developed a model of skin without follicles regrown dorsally on the hairless rat. Percutaneous absorption was compared, using a diffusion cell, in appendage-free skin relative to normal skin, and a predominant role of follicles for in vitro diffusion of [3H]hydrocortisone was noted. Results presented here of in vitro diffusion of tritiated hydrocortisone, niflumic acid, caffeine, and p-aminobenzoic acid, applied in acetone, confirm that appendageal diffusion is the major pathway in hairless rat skin. In the absence of follicles, the steady-state flux and the amounts diffusing in 24 or 48 h are 2-4 times lower than in normal skin. These results were confirmed in a second model in which diffusion of [3H]hydrocortisone was studied on skin samples taken one day after birth, at which time rat skin is still devoid of follicles, relative to five-day postnatal skin samples, in which follicles are fully developed. The steady-state flux and the total diffusion in 24 h were fivefold lower in follicle-free skin. These results support the view that follicles may have a far greater importance in percutaneous absorption than is generally assumed.

Transfollicular percutaneous absorption. Skin model for quantitative studies.

Theoretically percutaneous absorption comprises two components: the transepidermal route and the transappendageal route, so-called 'shunt' diffusion. The relative importance of 'shunt' diffusion was investigated with a model of appendage-free skin. After treatment with 60 degrees C water for exactly 1 min, hairless dorsal rat skin regrows as a continuous epidermis. We present preliminary results of hydrocortisone diffusion in vitro, in appendage-free skin relative to normal skin. With intact skin under our experimental conditions, the steady-state flux and the total diffusion in 24 h were 50-fold larger.