The chemical stability of pressurized Metered Dose Inhaler (pMDI) solution formulations can be affected by many variables, such as packaging components, formulation composition, and manufacturing process. Screening all the variables that could potentially have an impact on the chemical stability of the active ingredients can imply a heavy workload, high costs, and a very time consuming step in formulation feasibility. In this paper, a traditional approach for the screening of variables is compared against a multivariate approach.  These 4 variables, valve type, canister type, headspace air presence, and storage conditions, were investigated for their influence on active ingredient chemical stability. In particular, 4 different types of canister, 3 different types of valve, the presence or removal of the air in the canister headspace, and 2 different types of storage conditions were considered. All samples were manufactured using two-stage pressure filling equipment; using a validated HPLC/UV method, the active ingredient % residue assay versus the time zero value was evaluated as a main response. One Variable at A Time (OVAT) and Design of Experiment (DoE) approaches were compared.  Among the possible DoE, D-Optimal design was selected. To evaluate the chemical stability using the OVAT approach, all 48 (4 x 3 x 2 x 2) possible variable configurations were tested in triplicate (144 tested samples),
whereas the application of only the D-Optimal Design would have required merely 48 samples.
It was demonstrated that the application of the D-Optimal Design allows one to obtain easily interpretable information reducing the workload by about 70%.