title: Stability of sulforaphane for topical formulation.
abstract: BACKGROUND
  Sulforaphane (SFN) is a natural compound that has been investigated as a chemopreventive agent. SFN has been shown to inhibit the activator-protein-1 (AP-1) transcription factor and may be effective for inhibition of ultraviolet (UV) induced skin carcinogenesis. This study was designed to investigate the stability of SFN as a function of pH, temperature and in various solvents and formulations.
  
  
  METHODS
  Stability was analyzed using high-performance liquid chromatography. A potential lead formulation was identified and evaluated in vivo.
  
  
  RESULTS
  SFN was determined to undergo apparent first-order degradation kinetics for the conditions explored. It was observed that SFN undergoes base catalyzed degradation. Buffer species and solvent type impacts stability as well. SFN was found to be very sensitive to temperature with degradation rate changing by a factor of nearly 3.1 for every 10 °C change in temperature (at pH 4.0). SFN completely degraded after 30 days in a conventional pharmaceutical cream formulation. Improved stability was observed in organic formulation components. Stability studies were conducted on two nonaqueous topical formulations: a polyethylene glycol (PEG) ointment base and an organic oleaginous base.
  
  
  CONCLUSIONS
  Topically applied SFN in the PEG base formulation significantly reduced AP-1 activation after UV stimulation in the skin of a transgenic mouse model, indicating that SFN in this formulation retains efficacy in vivo.
authors.affiliation: College of Pharmacy, University of Arizona , Tucson, AZ , USA .
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Franklin
authors.forename: Sally E
authors.initials: SE
authors.lastname: Dickinson
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Karlage
authors.forename: G T
authors.initials: GT
authors.lastname: Bowden
authors.forename: Paul B
authors.initials: PB
authors.lastname: Myrdal
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D004356:Drug Storage; D005260:Female; D006863:Hydrogen-Ion Concentration; D017879:Isothiocyanates / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D008822:Mice, Transgenic; D011092:Polyethylene Glycols / Q000737:chemistry; D012867:Skin / Q000187:drug effects / Q000528:radiation effects; D012997:Solvents / Q000737:chemistry*; D013454:Sulfoxides; D013696:Temperature; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors*; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D012997:Solvents; D013454:Sulfoxides; D018808:Transcription Factor AP-1; D011092:Polyethylene Glycols; C016766:sulforaphane