3(3) factorial design-based optimization of the formulation of nitrofurantoin microcapsules.

A microcapsule form of nitrofurantoin was prepared by a simple coacervation method with carboxymethylcellulose and aluminium sulfate. 3(3) factorial design was performed for three independent variables, namely, the particle size of the drug, the size of the microcapsules and the pH of the dissolution medium. The dissolution tests with the formulated microcapsules were carried out according to the United States Pharmacopeia XXII rotating basket method at pH 1.2, 5, and 7.5, which represent the pH of gastrointestinal fluids. Release data were examined kinetically and the ideal kinetic models were estimated and t(63.2) values obtained from RRSBW distribution were used in the factorial design experiment. The influence of the independent variables on the dissolution of nitrofurantoin microcapsules could be expressed as the pH of the dissolution medium > particle size of the microcapsule > particle size of nitrofurantoin. The other aim of this study was to evaluate microcapsule formulation in terms of the United States Pharmacopeia criteria with a minimum of experiments. Our findings suggest that dosage forms which comply with the pharmacopoeia criteria for dissolution can be prepared and selected by factorial design.