title: Spray-dried oil-in-water emulsion to improve the intestinal absorption and oral bioavailability of ZLR-8, a nitric oxide-releasing derivative of diclofenac.
abstract: OBJECTIVE
  Spray-dried emulsion (SDE) was prepared and characterized to improve the intestinal absorption and oral bioavailability of ZLR-8, a nitric oxide-releasing derivative of diclofenac, currently under preclinical development.
  
  
  METHODS
  The intestinal absorption of ZLR-8 was characterized by single pass intestinal perfusion technique to obtain its absorption and permeability parameters. SDE of ZLR-8 was prepared and characterized by particle size measurements and in-vitro release study. Accurate and precise RP-HPLC methods for the detection of ZLR-8 and its metabolite diclofenac were constructed to perform the bioavailability study.
  
  
  RESULTS
  It was demonstrated that ZLR-8 was absorbed in the whole intestine, of which the duodenum segment exhibited the largest absorption ability. ZLR-8 can be classified into BCS Class 2. SDE significantly enhanced the intestinal absorption rate of ZLR-8 in duodenum and jejunum but had indistinctive effect on permeability. All concentrations of ZLR-8 in rat plasma was lower than the limit of detection. A bicompartment model gave the best fit to the plasma diclofenac concentration-time curves. Calculated on AUC(0-12h) , the mean relative bioavailability of SDE was 105.4-fold that of ZLR-8 suspension.
  
  
  CONCLUSIONS
  SDE significantly improved the intestinal absorption of ZLR-8 and resulted in a dramatic improvement in its bioavailability.
authors: Department of Pharmaceutics, China Pharmaceutical University, Nanjing, China.
authors: Jianjun
authors: J
authors: Zhang
authors: Zengjuan
authors: Z
authors: Zheng
authors: Yuan
authors: Y
authors: Gao
authors: Yihua
authors: Y
authors: Zhang
mesh_terms: D000465:Algorithms; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D003890:Desiccation; D004008:Diclofenac / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D004655:Emulsions / Q000737:chemistry*; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D020030:Nitric Oxide Donors / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D010316:Particle Size; D010539:Permeability; D019999:Pharmaceutical Solutions; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004655:Emulsions; D020030:Nitric Oxide Donors; D019999:Pharmaceutical Solutions; C520529:ZLR-8 compound; D004008:Diclofenac