title: Evaluation of diclofenac prodrugs for enhancing transdermal delivery.
abstract: Abstract Objective: The purpose of this study was to evaluate the approach of using diclofenac acid (DA) prodrugs for enhancing transdermal delivery.
  
  
  METHODS
  Methanol diclofenac ester (MD), ethylene glycol diclofenac ester (ED), glycerol diclofenac ester (GD) and 1,3-propylene glycol diclofenac ester (PD) were synthesized and evaluated for their physicochemical properties such as solubilities, octanol/water partition coefficients, stratum corneum/water partition coefficients, hydrolysis rates and bioconversion rates. In vitro fluxes across human epidermal membrane (HEM) in the Franz diffusion cell were determined on DA-, MD-, ED-, GD- and PD-saturated aqueous solutions.
  
  
  RESULTS
  The formation of GD and ED led to the prodrugs with higher aqueous solubilities and lower partition coefficients than those of the parent drug. Prodrugs with improved aqueous solubility showed better fluxes across HEM in aqueous solution than that of the parent drug, with GD showing the highest aqueous solubility and also the highest flux. There is a linear relationship between the aqueous solubility and flux for DA, ED and PD, but GD and MD deviated from the linear line.
  
  
  CONCLUSIONS
  Diclofenac prodrugs with improved hydrophilicity than the parent drug could be utilized for enhancing transdermal diclofenac delivery.
authors: Department of Biomedical and Pharmaceutical Sciences, Idaho State University , Pocatello, ID , USA.
authors: Shabbir
authors: S
authors: Lobo
authors: Henan
authors: H
authors: Li
authors: Nashid
authors: N
authors: Farhan
authors: Guang
authors: G
authors: Yan
mesh_terms: D000279:Administration, Cutaneous; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004008:Diclofenac / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D004952:Esters / Q000737:chemistry; D006801:Humans; D006868:Hydrolysis; D011355:Prodrugs; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004952:Esters; D011355:Prodrugs; D014867:Water; D004008:Diclofenac