title: Topical delivery of a naproxen-dithranol co-drug: in vitro skin penetration, permeation, and staining.
abstract: OBJECTIVE
  This work probed the topical delivery and skin-staining properties of a novel co-drug, naproxyl-dithranol (Nap-DTH), which comprises anti-inflammatory (naproxen) and anti-proliferative (dithranol) moieties.
  
  
  METHODS
  Freshly excised, full-thickness porcine ear skin was dosed with saturated solutions of the compounds. After 24 h, the skin was recovered and used to prepare comparative depth profiles by the tape-stripping technique and to examine the extent of skin staining.
  
  
  RESULTS
  Depth profiles showed that Nap-DTH led to a 5-fold increase in drug retention in the skin compared to dithranol. The application of Nap-DTH also demonstrated improved stability, resulting in lower levels of dithranol degradation products in the skin. Furthermore, significantly less naproxen from hydrolysed Nap-DTH permeated into the receptor phase compared to naproxen when applied alone (0.08 ± 0.03 nmol cm(-)² and 180 ± 60 nmol cm(-)², respectively). Moreover, the reduced staining of the skin was very apparent for Nap-DTH compared to dithranol.
  
  
  CONCLUSIONS
  Topical delivery of Nap-DTH not only improves the delivery of naproxen and dithranol, but also reduces unwanted effects of the parent moieties, in particular the skin staining, which is a major issue concerning the use of dithranol.
authors.affiliation: Welsh School of Pharmacy, Cardiff University, Cardiff, UK. w.lau@reading.ac.uk
authors.forename: Wing Man
authors.initials: WM
authors.lastname: Lau
authors.forename: Alex W
authors.initials: AW
authors.lastname: White
authors.forename: Charles M
authors.initials: CM
authors.lastname: Heard
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000875:Anthralin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D003879:Dermatologic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004355:Drug Stability; D066298:In Vitro Techniques; D057230:Limit of Detection; D009288:Naproxen / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010539:Permeability; D012867:Skin / Q000378:metabolism*; D012995:Solubility; D013194:Staining and Labeling; D013552:Swine
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003879:Dermatologic Agents; D009288:Naproxen; D000875:Anthralin