A rheological assessment of the nature of interactions between mucoadhesive polymers and a homogenised mucus gel.
The ability of mucoadhesive materials to produce a large increase in the resistance to deformation when incorporated into a mucus gel, relative to when the mucus gel and test materials are evaluated separately at the same concentration, has been reported in several previous studies. It has been proposed that this phenomenon, termed rheological synergism, can be used as a measure of the strength of the mucoadhesive interaction. This study investigated the interactions between four putative mucoadhesive polymers (Noveon, Pemulen TR-2, carageenan and sodium carboxymethylcellulose) and a homogenised mucus gel, using dynamic oscillatory rheology. It was shown that, with the exception of sodium carboxymethylcellulose, incorporating a mucoadhesive polymer into a mucus gel produces rheological behaviour indicative of a weakly cross-linked gel network, which suggested a structure containing physical chain entanglements and non-covalent (probably hydrogen) bonds. Optimum gel strengthening occurred in a weakly acidic environment, suggesting an optimum conformation and degree of ionisation of the polymer and mucus molecules. Subsequent work suggested that the macromolecular interactions between polymer and mucus are sensitive to temperature, with the dynamic moduli decreasing with increasing temperature, further indicating bonding of a non-covalent nature. This work provide further evidence that rheological methods can be used as a tool to evaluate the interactions between a mucoadhesive macromolecule and a mucus gel. It also adds to the perception that molecular interpenetration may be an important factor in mucoadhesion by strengthening the mucus in the mucoadhesive/mucosal interfacial layer.
Department of Analytical and Pharmaceutical Chemistry, The Royal Danish School of Pharmacy, Copenhagen. fm@mail.dfh.dk
F
F
Madsen
K
K
Eberth
J D
JD
Smart
D000180:Acrylic Resins / Q000737:chemistry*; D000818:Animals; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry*; D002351:Carrageenan / Q000737:chemistry*; D005753:Gastric Mucosa / Q000378:metabolism; D005782:Gels / Q000737:chemistry; D009093:Mucus / Q000737:chemistry*; D012212:Rheology; D013552:Swine
D000180:Acrylic Resins; D005782:Gels; C030312:calcium polycarbophil; D002351:Carrageenan; D002266:Carboxymethylcellulose Sodium