Supersaturation: enhancement of skin penetration and permeation of a lipophilic drug.
OBJECTIVE
To increase the dermal delivery of a lipophilic model compound (LAP), and to deduce the underlying mechanism of enhanced absorption.


METHODS
Penetration of LAP from mixtures of up to four degrees of saturation into the stratum corneum was evaluated using a tape-stripping method; epidermal permeation of the drug was measured in Franz diffusion cells. The relative diffusion and stratum corneum-vehicle partition coefficients of LAP were determined by fitting the results to the appropriate solutions to Fick's second law of diffusion.


RESULTS
Both the skin permeation rate and the amount of LAP in the stratum corneum increased linearly with increasing degree of saturation. The apparent diffusivity and its partition coefficient deduced from the penetration experiments were independent of the degree of saturation of the drug in the applied formulation, and consistent with corresponding parameters derived from the permeation experiments.


CONCLUSIONS
Supersaturation can increase the skin penetration and permeation of lipophilic drugs. The diffusion and partition parameters deduced for LAP indicate that supersaturation acts exclusively via increased thermodynamic activity without apparent effect on the barrier function of the skin per se.
Moser
K
K
Novartis Pharma AG, Technical R&D/PHAD, Basel, Switzerland.
Kriwet
K
K
Froehlich
C
C
Kalia
Y N
YN
Guy
R H
RH
D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D004817:Epidermis / Q000378:metabolism*; D008055:Lipids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010539:Permeability; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019946:Propylene Glycol / Q000008:administration & dosage / Q000493:pharmacokinetics; D012869:Skin Absorption / Q000502:physiology*; D013552:Swine
D008055:Lipids; D014677:Pharmaceutical Vehicles; D019946:Propylene Glycol