Quality by Design: Concept for the Proof-of-Principle Testing Regarding Automated Microdosing

More and more capsules have to be filled with a low volume of highly active pharmaceutical ingredients, which can cause difficulties in fulfilling the given release specifications, such as content uniformity. Quality by Design (QbD) was used in order to define a process window for dosing low quantities of a typical inhalation product in order to launch new high-speed microdosing equipment for the process of microdosing powders into capsules. QbD is a well-known tool used by the pharmaceutical industry for formulation or process optimization as a scientific, risk-based, holistic, systematic, and proactive approach to product testing. The test plan was created by statistical software. The described QbD trials were then tested and analyzed according to different parameters such as quality of lactose, fill volume, applied vacuum, different vacuum dosing wheels, and fill amounts. The results were examined by macroscopic evaluation, fill weight, particle size distribution, rheological powder properties and their statistical analysis. The analysis of variance investigated the main effects and interactions that influence the fill weight and particle size distribution. It was the aim of this paper to gain results on the influence of equipment and process parameters on fill weight and particle size distribution as insight for further similar projects.