IMPLEMENTATION OF EXPERIMENTAL DESIGN METHODOLOGY IN THE COMPATIBILITY STUDY OF HYDROCORTISONE WITH SELECTED EXCIPIENTS USED IN SOLID DOSAGE FORMS

The aim of the study was to assess the usefulness and the possibility of application of experimental design methodology (DoE) in defining the qualitative composition of a pharmaceutical formulation containing hydrocortisone as the active pharmaceutical ingredient. Eight multi-component mixtures were prepared according to the matrix generated by means of the fractional factorial design. Four types of excipients (binders, disintegrants, fillers and glidants) were used as input variables. In order to accelerate the possible chemical changes in the chemical structure of hydrocortisone, the prepared mixtures were exposed to the temperature of 50 degrees C and humidity of 50% RH for 3 months. The evaluation of the chemical interactions, expressed by the hydrocortisone degradation, was monitored using high-performance liquid chromatography. The DoE approach allowed for the selection of optimal excipients. The fractional factorial design as a knowledge discovery method provides useful clues for the formulation analysts and thus this approach can be taken into consideration in order to support rational decision making in the field of pharmaceutical technology.