In vivo percutaneous absorption: a key role for stratum corneum/vehicle partitioning

Abstract

Percutaneous absorption of five compounds was studied in the hairless rat in vivo: benzoic acid, caffeine, hydrocortisone, inulin and thiourea. The results clearly demonstrate that, as with in vitro experiments, a steady-state flux can be achieved in vivo. This steady-state flux is strongly molecule dependent. Thus, the values for inulin and benzoic acid differ by a factor of about 40. In contrast, although the physicochemical properties of the studied compounds vary widely, their lag times were not significantly different. The mean lag time was 11 +/- 2 min. Different compounds could be considered to have approximately the same apparent diffusion coefficient with regard to their percutaneous absorption in vivo. Thus, for a given thickness of stratum corneum and a given anatomical site, the penetration flux value of a substance depends only on its stratum corneum/vehicle partition coefficient. Using a classical model, we have demonstrated that the amount of substance present in the stratum corneum (Qsc) at equilibrium (30 min) is related to this partition coefficient. There is also a linear relationship between steady-state flux and Qsc. In practice, the in vivo steady-state flux of penetration of a compound can be predicted from the simple measurement of the amount present in the stratum corneum after a contact time of 30 min.

Comparison of the Bioactivity of Mometasone Furoate 0.1% Fatty Cream, Betamethasone Dipropionate 0.05% Cream and Betamethasone Valerate 0.1% Cream in Humans

“…Mom etasone furoate is strongly lipophilic, which seems to be associated with a high penetration rate [20]. The composition of different cream vehicles has previously been shown to in fluence the effect of topical steroids pro foundly [17], Although a direct correlation between lipophilicity (partition coefficient of solvent/water) and the permeability constant cannot always be established, there is an em pirically good correlation between these two parameters within the same class of com pounds. The partition coefficient (P) of mometasone furoate in octanol/water is (log P) = 3.8 and for betamethasone valerate (log P) = 3.6.…”

“…The EEC classification of topical cortico steroid preparations is based on a series of dif ferent properties, mainly different chemical modifications of the steroid molecule [13,17], These may strongly affect the penetra tion, binding and biodegradation properties of the compounds. Also the composition of the vehicle has a substantial influence on the potency of topical preparations [14][15][16], Since the introduction of corticosteroids, chemical engineering has provided a series of optimized steroid molecules for topical prep arations [16,20], Mometasone furoate is a recently introduced synthetic corticosteroid in which the steroid nucleus is a 16-methyl analogue of beclomethasone with a 21 -chloro group and a novel (2') furoate 17-ester.…”

Solid Lipid Nanoparticles as Effective Reservoir Systems for Long-Term Preservation of Multidose Formulations

“…First of all, the minimal inhibitory concentration values (MIC100), defined as the lowest preservative concentration that prevented any discernible growth with respect to the control, relative to single parabens and to mixtures of PP and BP are reported in Table III. As already known from the literature (20), BP is more active than PP as a preservative. Furthermore, the associations of PP and BP show the same MIC value of BP alone.…”

Difference in Percutaneous Absorption and Intracutaneous Distribution in Guinea Pigs among Topical Antifungal Drugs (Tioconazole Solution, Tioconazole Cream, Miconazole Nitrate Solution and Bifonazole Solution)

“…This difference is considered to be the cause of the different percutaneous penetration of these drugs. Rougier et al 30) and Surber et al 31) have reported that the penetration flux value of a substance depends on its partition coefficient between stratum corneum and vehicle. The difference of percutaneous penetration among these four formulations may originate in the difference of their ingredients.…”