Development of foaming vaginal tablets with clotrimazole. Part I. Optimization of the formulation using design of experiments approach

Objectives. The aim of this study was to optimize the formulation of certain immediate release foaming vaginal tablets, with fast vaginal disintegration (part I), fallowing their time stability (part II). Material and methods. Modde optimizing software and a Box-Bhenken experimental design was used to establish an optimal formula that would provide maximum “in vitro” behaviour advantages, including stability during preservation; and the improvement of the foaming effect. There were prepared 15 formulations of foaming vaginal tablets in order to choose the optimal formula. Outcomes. The main factor, with influence over all the studied parameters, is the percentage of the effervescent mixture in the formulation. The excess of citric acid has a main role in the assurance of local pH; in the improvement of the flowing properties of the powder mixtures before compression; and in the improvement of the effervescent process, having, on the other hand, an effect of decreasing the stability of tablets and increasing their humidity adsorption. Sodium lauryl sulphate, at the chosen concentration levels (0.5-1.5%), did not influence the dependent variables, it only produced a strong-er resistance of the foam. The optimal formula of a foaming vaginal tablet with an optimal stability during preservation must contain 0.5% sodium lauryl sulphate, while the effervescent mixture must contain a percentage of 24% excess of citric acid, and it must represent 44% of the total amount of excipients. Conclusions. The experimental determinations of the optimal formula were close to the theoretical values predicted by the program, this certifying the validity of the optimization and the conclusion draw after analysis the experimental design.