Comparison of the mucoadhesive properties of various polymers

Abstract

In this study the mucoadhesive potential of nineteen different, most often referred mucoadhesive polymers was evaluated and characterized by adhesion time and total work of adhesion (TWA) of the polymer to porcine small intestinal mucosa. In addition, the influence of pH of the polymer and of method of drying on adhesion was evaluated. Aqueous polymer solutions were therefore adjusted to pH 3.0 and 7.0. Solutions were either dried by lyophilization (lyo.) or precipitated (pr.) in organic solvent and air-dried. Results of this study led to the following rank order of adhesion time: chitosan-4-thiobuthylamidine pH 3 lyo. > chitosan-4-thiobuthylamidine pH 6.5 pr. > polycarbophil-cysteine pH 3 lyo. > chitosan-4-thiobuthylamidine pH 6.5 lyo. > PAA₄₅₀-cysteine pH 3 lyo. > pH 7 pr. > Carbopol 980 pH 7 pr. > Carbopol 974P pH 7 pr. > polycarbophil pH 7 pr. > 980 pH 3 lyo. The rank order obtained for adhesion time was in agreement with the rank order obtained for total work of adhesion. The highest mucoadhesion was shown by thiolated polymers at pH 3.0, dried by lyophilization. In contrary, polyacrylates were most mucoadhesive in form of precipitated neutral sodium salts. Other tested polymers like natural polysaccharides, cellulose derivatives, polyvinylpirrolidone and polyethylenglycole, although previously reported as good mucoadhesives, showed low to almost no mucoadhesion. The pH of polymer and drying method were found to be important factors influencing the mucoadhesive potential of polymers.

Introduction

Mucoadhesive polymers are synthetic or natural macromolecules which are capable of attaching to mucosal surfaces. The concept of mucoadhesive polymers has been introduced into the pharmaceutical literature more than 40 years ago and nowadays it has been accepted as a promising strategy to prolong the residence time and to improve the specific localization of drug delivery systems on various membranes. So far, a considerable number of studies focusing on the mucoadhesive properties of a wide range of polymeric materials have been performed using different in vitro methods and techniques [1]. Standard in vitro tests used to compare and describe mucoadhesive properties involve measurements of peel, stress, tensile forces [2] necessary to detach a polymer formulation from mucosa, contact angle measurements and evaluation of physicochemical properties of polymers. Consequently, these various approaches resulted in great variability of data, causing much confusion and discussions in this research field. Different groups working with different experimental methods have reported about widely differing results in terms of polymer mucoadhesiveness. For instance, in the case of sodium carboxymethylcellulose Caramella et al. [2] reported about its satisfactory mucoadhesive properties, Smart et al. [3] claimed excellent mucoadhesive properties and Lehr et al. [4] found that it was poorly mucoadhesive. However, the incoherency of the data may not only be due to the different approaches but also due to the individual interpretation of results.

The aim of this study was therefore to evaluate the mucoadhesive properties of the nineteen most referred mucoadhesive polymers by two different methods and to compare them with each other. In previous studies the pH of the polymer has been recognized as one of the major factors influencing the mucoadhesive bond of anionic and cationic polymers [5]. Therefore the polymers were tested at two different pHs, namely at pH 3.0 and 7.0. The importance of the ability of the polymer to take up water from the mucus has been shown to be a primary determinant of mucoadhesion [6]. The rate of water uptake may be related to the mean pore diameter of the formulation [7], which is, inter alia, determined by drying method [8]. In order to assess also the significance of drying method each polymer was evaluated in both lyophilized and air-dried form.