Use of factorial design for evaluation of factors affecting the chemical stability of sirolimus (rapamycin) in solid dosage form.

Effects of four process and formulation parameters (spraying rate of ethanol solution, drying and tablet hardness and hydroxypropyl methyl cellulose (HPMC) content) were evaluated in terms of initial quality of tablets using factorial design approach. For determination of stability of final drug product, the tablets were exposed to stress testing conditions and the three most significant factors were investigated (spraying rate of ethanol solution, drying and HPMC content). Considering the chemical stability of Sirolimus, the following responses were found to be most important: total sum of degradation products, levels of impurity I and assay of isomer C. Investigated factors and their interactions most significantly affected the assay of isomer C in initial and in stressed stability testing samples. The factorial design approach is a very economic way of obtaining the maximum amount of information in a short period of time, which is especially important in studies that include a variety of different factors and their interactions.