Limitations of the rheological mucoadhesion method: the effect of the choice of conditions and the rheological synergism parameter.

This work demonstrates several limitations of the simple rheological method that is widely used to investigate mucoadhesion of polymer gels. We establish the importance of the choice of conditions and the synergism parameter for the results obtained in comparative studies. Dynamic rheological measurements were performed on gels based on four slightly different poly(acrylic acid) (Carbopol) polymers and their corresponding mixtures with porcine stomach mucin and bovine submaxillary gland mucin. The rationale for the comparison of the polymers had a large influence on the results obtained. The method does not give the same ranking order when two different comparison strategies are used. Moreover, we show that the results obtained are also sensitive to where in the 'rheological range' the comparison is made, e.g., at which value of G'. Positive values of the synergism parameters are, for example, only seen with weak gels. The choice of synergism parameter also has a bearing on the results obtained, and here we suggest a new refined relative parameter, the log ratio (log(G'(mix)/G'(p))). We also investigated the adhesion of the gel preparations to porcine nasal mucosa, using tensile strength measurements. Increased gel strength resulted in stronger adhesion, which is in contrast to the results from the rheological method, where the positive values of the synergism parameters were seen only with weak gels. On the basis of the limitations demonstrated and discussed, we recommend that the rheological method should not be used as a stand-alone method for the studying of mucoadhesive properties of polymer gels.