Experimental design methodologies in the development of mucoadhesive wafers loaded with econazole

The aim of this work was to develop mucoadhesive wafers loaded with econazole for the treatment of oral candidiasis. Lyophilized wafers are an innovative drug delivery system able to form hydrogels on contact with saliva and to ensure a controlled drug release. Econazole is an imidazole antifungal agent very poorly water soluble. For this reason, in order to improve its dissolution properties, it was added to the wafers as coground product with sulfobutylether-β-cyclodextrin and citric acid. The traditional approach for developing a new formulation is to change one variable at a time (OVAT), but this method suffers from several pitfalls, being strenuous, uneconomical, and unable to reveal interactions between the factors. In this study experimental design methodologies (DoE) were applied in order to overcome most shortcomings inherent to the traditional OVAT approach. A screening design was used at the beginning of the experimental procedure to reveal whether the formulation factors evaluated (pectin kind and carboxymethyl cellulose (CMC) and pectin amount) had an influence on the responses (residence time and adhesive strength to excised porcine mucosa) and to identify their appropriate ranges. From this study it was found that the kind of pectin does not significantly affect the mucoadhesive properties of the wafers; for this reason this variable was not considered in the next experimental stage (optimization phase). After the initial screening, response surface methodology was used to predict the response values for all possible combinations of factors within the experimental region, and to identify the optimal composition. A Central Composite Design was applied, since it makes it possible to obtain response surface plots, which can be easily investigated to individuate the optimal point. The best composition of the wafer, obtained by application of Derringer's desirability function, was the following: amidated pectin 7.2%(w/w) and CMC 5.2%(w/w). The experimental values of adhesive strength (28.4 0.04 g/cm2) and residence time (88.10.1 min) given by the optimized formulation were very close to the predicted values, thus demonstrating the validity of the applied model.