Oesophageal bioadhesion of sodium alginate suspensions: particle swelling and mucosal retention.
This paper describes a prospective bioadhesive liquid dosage form designed to specifically adhere to the oesophageal mucosa. It contains a swelling polymer, sodium alginate, suspended in a water-miscible vehicle and is activated by dilution with saliva to form an adherent layer of polymer on the mucosal surface. The swelling of alginate particles and the bioadhesion of 40% (w/w) sodium alginate suspensions were investigated in a range of vehicles: glycerol, propylene glycol, PEG 200 and PEG 400. Swelling of particles as a function of vehicle dilution with artificial saliva was quantified microscopically using 1,9-dimethyl methylene blue (DMMB) as a visualising agent. The minimum vehicle dilution to initiate swelling varied between vehicles: glycerol required 30% (w/w) dilution whereas PEG 400 required nearly 60% (w/w). Swelling commenced when the Hildebrand solubility parameter of the diluted vehicle was raised to 37 MPa(1/2). The bioadhesive properties of suspensions were examined by quantifying the amount of sodium alginate retained on oesophageal mucosa after washing in artificial saliva. Suspensions exhibited considerable mucoretention and strong correlations were obtained between mucosal retention, the minimum dilution to initiate swelling, and the vehicle Hildebrand solubility parameter. These relationships may allow predictive design of suspensions with specific mucoretentive properties, through judicious choice of vehicle characteristics.
Formulation Insights, School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
J Craig
JC
Richardson
Peter W
PW
Dettmar
Frank C
FC
Hampson
Colin D
CD
Melia
D000269:Adhesives / Q000494:pharmacology*; D000464:Alginates / Q000494:pharmacology*; D000465:Algorithms; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004947:Esophagus; D066298:In Vitro Techniques; D007700:Kinetics; D009092:Mucous Membrane / Q000378:metabolism; D010316:Particle Size; D012995:Solubility; D013535:Suspensions; D013552:Swine
D000269:Adhesives; D000464:Alginates; D013535:Suspensions