Comparative mucoretention of sucralfate suspensions in an everted rat esophagus model.
A simple, rapid, and reproducible in vitro model was established to quantify the relative esophageal mucoadhesive properties of viscous liquid formulations, and the model was applied to compare marketed sucralfate suspensions (Gastrogel, Antepsin, and Ulcogant) to better understand differences in clinical performance. Rat esophageal mucosal segments were everted onto a glass rod and briefly immersed into a liquid formulation containing 51Cr microspheres. Indirect quantification of the retained formulation provided excellent recovery (98.7-101%) and reasonable precision (1.06-38.3% CV). Mucosal retention profiles of the formulations were determined by rinsing the coated tissue in relevant gastrointestinal fluids using the technique of reciprocating vertical immersion. Dispersions of the mucoadhesive hydrogel Carbopol 934P were employed to initially characterize the performance of the model with respect to composition of the rinse fluids, and type and amount of shear force during rinsing. Retention of Carbopol was sensitive to the mechanics of rinsing and to salivary salts but not mucin in the rinse medium. A sucralfate gel suspension (Gastrogel) showed much greater mucoadhesion and resistance to removal by saliva than two non-gel suspensions (Antepsin, Ulcogant). Results suggest that in situ gelation may be a contributing mechanism for strong esophageal retention. These in vitro results are in general agreement with published human esophageal retention data on similar sucralfate suspensions and lend credence to the everted rat esophagus as a qualitatively predictive in vitro model for development of esophageal mucoadhesive liquids.
Dobrozsi
D J
DJ
College of Pharmacy, University of Cincinnati Medical Center, 3223 Eden Avenue, Cincinnati, OH 45267-0004, USA. dobrozsi.dj@pg.com
Smith
R L
RL
Sakr
A A
AA
D000268:Adhesiveness; D000818:Animals; D002626:Chemistry, Pharmaceutical; D004947:Esophagus / Q000378:metabolism*; D005765:Gastrointestinal Agents / Q000493:pharmacokinetics*; D008297:Male; D008954:Models, Biological; D009092:Mucous Membrane; D051381:Rats; D017207:Rats, Sprague-Dawley; D013392:Sucralfate / Q000493:pharmacokinetics*; D013535:Suspensions
D005765:Gastrointestinal Agents; D013535:Suspensions; D013392:Sucralfate