PURPOSE: 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.
PURPOSE: 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.
Authors: Ryan F Donnelly; Thakur Raghu Raj Singh; Michael M Tunney; Desmond I J Morrow; Paul A McCarron; Conor O'Mahony; A David Woolfson Journal: Pharm Res Date: 2009-09-11 Impact factor: 4.200
Authors: Ryan F Donnelly; Thakur Raghu Raj Singh; Ahlam Zaid Alkilani; Maelíosa T C McCrudden; Shannon O'Neill; Conor O'Mahony; Keith Armstrong; Nabla McLoone; Prashant Kole; A David Woolfson Journal: Int J Pharm Date: 2013-05-01 Impact factor: 5.875
Authors: Siegfried Segaert; Neil H Shear; Andrea Chiricozzi; Diamant Thaçi; Jose-Manuel Carrascosa; Helen Young; Vincent Descamps Journal: Dermatol Ther (Heidelb) Date: 2017-08-07
Authors: Eliana B Souto; Joana F Fangueiro; Ana R Fernandes; Amanda Cano; Elena Sanchez-Lopez; Maria L Garcia; Patrícia Severino; Maria O Paganelli; Marco V Chaud; Amélia M Silva Journal: Heliyon Date: 2022-02-11