The production of nanosuspensions via stirred‐media milling has proved to be an effective method to overcome bioavailability challenges of poorly water‐soluble active pharmaceutical ingredients (APIs). The fine‐grinding of the APIs cinnarizine and fenofibrate was investigated. Important process parameters were varied and the influence on product quality was studied. Different challenges were identified prior to and during milling: Foaming inside the milling equipment and agglomeration of fenofibrate occurred, and a long‐term grinding experiment for cinnarizine revealed an increase in particle size, caused by ripening of the drug crystals during milling. Thus, the stability against ripening during the process is a newly identified challenge for the fine‐grinding of APIs.
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