Influence of hydroxypropyl-beta-cyclodextrin on the transdermal permeation and skin accumulation of oxybenzone.
The objective of the present study was to determine the effects of hydroxypropyl-beta-cyclodextrin (HPCD) concentration on the transdermal permeation and skin accumulation of a model ultraviolet (UV) absorber, oxybenzone. The concentration of oxybenzone was held constant at 2.67 mg/mL for all formulations, while the HPCD concentrations varied from 0 to 20% (w/w). Complexation of oxybenzone by HPCD was demonstrated by differential scanning calorimetry. A modified Franz cell apparatus was used in the transdermal experiments, with aliquots of the receptor fluid assayed for oxybenzone by high-performance liquid chromatography. From the permeation data, flux of the drug was calculated. Skins were removed from the diffusion cells at specified time points over a 24-hr period and the oxybenzone content in the skin determined. The aqueous solubility of oxybenzone increased linearly with increasing HPCD concentration, following a Higuchi AL-type complexation. The stability constant of the reaction was calculated from the phase-solubility diagram and found to be 2047 M-1. As the concentration of HPCD was increased from 0 to 10%, transdermal permeation and skin accumulation of oxybenzone increased. Maximum flux occurred at 10% HPCD, where sufficient cyclodextrin was added to completely solubilize all oxybenzone. When the concentration of HPCD was increased to 20%, both transdermal permeation and skin accumulation decreased. These data suggest the formation of a drug reservoir on the surface of the skin.
Felton
Linda A
LA
University of New Mexico, Health Sciences Center, College of Pharmacy, 2502 Marble NE, Albuquerque, NM 87131, USA. lfelton@unm.edu
Wiley
Cody J
CJ
Godwin
Donald A
DA
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000279:Administration, Cutaneous; D000818:Animals; D001577:Benzophenones / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D002152:Calorimetry, Differential Scanning; D003505:Cyclodextrins / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005079:Excipients / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D051379:Mice; D008812:Mice, Hairless; D010539:Permeability / Q000187:drug effects; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D012995:Solubility; D012997:Solvents; D013473:Sunscreening Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D013816:Thermodynamics; D013997:Time Factors; D014867:Water; D047392:beta-Cyclodextrins
D001577:Benzophenones; D003505:Cyclodextrins; D005079:Excipients; D012997:Solvents; D013473:Sunscreening Agents; D047392:beta-Cyclodextrins; D014867:Water; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C005290:oxybenzone