Extended frequency sweep: A more realistic rheological approach to investigate the process of mucoadhesive polymer-mucus gel chain interpenetration

Mucoadhesive formulations have been of great interest in recent years. One approach to study mucoadhesion is the technique of dynamic oscillatory rheology (DOR). In this study the use of an extended frequency sweep DOR, instead of the routine limited DOR studies, as a more comprehensive and realistic means of investigating the process of mucoadhesion was investigated. For this purpose polymeric discs were directly placed in contact with natural mucus samples and incubated for various time intervals (15, 60 and 120 min) at 37degreesC, and then they were rheologically examined across a frequency of 0.0001-10 Hz. Results showed that in the presence of anionic mucoadhesive discs containing Carbopol 934P (C934) and sodium carboxymethyl cellulose (NaCMC), the G' (storage modulus) and to a smaller extent G" (loss modulus) values of the weakly viscoelastic mucus samples are strengthened much more than the non-ionic polymer hydroxypropyl cellulose and the calcium containing Carbopol EX83, and far less reduced at frequencies below 1 Hz. However, in the presence of potassium thiocyanate (hydrogen-bond breaking agent), unlike G" values, the G' values of particularly the anionic polymers C934 and NaCMC suffered a sharp decline at frequencies below 1 Hz. These findings support the theory of mucoadhesive polymer chain interpenetration and formation of hydrogen-bonds with the mucus gel network, and shows that by using an extended frequency sweep rather than a normal limited frequency sweep, a more detailed and realistic approach for studying the process of mucoadhesion and putative mucoadhesive polymers and formulations, could be provided.