Active pharmaceutical ingredient (API) milling is a key step in many drug development processes. Traditional dry milling technologies (i.e. media mills, pin mills) used for this application have come under increased scrutiny due to yield losses, hygiene concerns, process train portability as well as physical property instability due to surface defects, amorphous phase generation, and more. Wet milling equipment such as high pressure homogenizers and media mills overcome many challenges associated with dry milling, but are still restricted by low capacities, high energy consumption and frequent maintenance requirements.
In search of traditional wet milling technology alternatives, the Quadro® HV has been tested with multiple compounds provided by end users. API’s ranging in particle sizes, morphologies and mechanical properties were all examined with the Quadro® HV. The HV is a viable option as it can operate at 70m/s and offers more than 55 times the high shear energy of a traditional rotor/stator wet mill. The high precision of the HV also allows for accurate process scaling abilities from lab formulation, to pilot and production processing.
Using the Quadro® HV, API size reduction achieved a mean volume (mV) particle size distribution (PSD) of 5 – 25µm for compounds starting between 50 – 400µm, in comparison to 20-50 µm with a conventional 25 m/s high shear mixer. Increased tip speeds achieved an additional 30 – 60% reduction of mV and PSD for a wide range of APIs. Similar PSD profiles were also observed for tests that used a lower percentage of APIs (i.e. 20mg/ml vs. 100 mg/ml slurries).
Overall it was determined the restricted capacity, high energy consumption, and frequent maintenance requirements of traditional API milling methods can be overcome with the Quadro® HV, thus maximizing productivity while cutting development and production costs.
Learn more about the single source for complete biopharmaceutical manufacturing solutions that gathers 12,000 industry professionals each year.