Quality by design approach in the optimization of the spray-drying process.

CONTEXT/OBJECTIVE: The aim of this study was to illustrate the influence of the processing parameters, inlet temperature, atomization air flow rate and feed flow rate, on critical quality attributes of spray-dried powders using design of experiments (DoE).

METHODS: Spray-dried powders were characterized by laser diffraction, X-ray powder diffraction (XRPD) and near-infrared spectroscopy (NIR). Multivariate analysis of two different experimental designs was performed to elucidate the optimal process conditions.

RESULTS AND DISCUSSION: XRPD revealed that the spray-dried powders consisted of crystalline β-mannitol and amorphous trehalose. Non-invasive NIR measurement was successfully used for correlating the critical quality attribute particle size with size determined by laser diffraction. The full factorial design proved to be unsuitable due to the non-linear influence of factors. The composite face-centered design improved the quality of the models and showed both linear and non-linear influence of the parameters on the outcomes. A model explaining the influence of the factors on all quality attributes showed similar results as the models optimized for a single response.

CONCLUSION: This study showed the applicability of DoE for the investigation of spray-dried powders. The knowledge of the interplay between process parameters and quality attributes will enable rational process design to achieve a desired outcome.