Using different experimental designs in drug-excipient compatibility studies during the preformulation development of a stable solid dosage formulation.

Different types of factorial experimental designs can be used in compatibility studies of drug development, where many different factors and their interactions should be evaluated to predict their effects on the degradation of the drug substance under study. All possible main and interaction effects of different potential excipients that can constitute the drug product should be evaluated in order to select the best combination of excipients that give the lowest possible degradation, i.e., the most stable drug product. Statistical experimental designs enable the user to obtain the maximum amount of information, i.e., the degradation effects of excipients and their interactions on the stability of the drug substance, on the basis of the smallest possible number of experiments. The use of full and two different fractional factorial designs is described using a real example where the excipients that stabilize the drug substance or cause as little degradation as possible are selected for a solid dosage formulation. It was shown that the type and the sequence of design used during the studies are also important to get reliable and valuable results. A thorough explanation of the statistical evaluation of data and different presentations of final solutions are given.