Engineering of acetaminophen particle attributes using a wet milling crystallisation platform

Area of Science:

• Chemical Engineering
• Crystallization Science
• Particle Technology

Background:

• Controlling particle attributes is crucial in pharmaceutical manufacturing.
• Wet milling and crystallization are key processes for particle engineering.
• Acetaminophen crystal properties influence its bioavailability and formulation.

Purpose of the Study:

• To investigate the impact of wet milling and crystallization conditions on acetaminophen particle characteristics.
• To achieve enhanced control over particle size, shape, and surface energy.
• To demonstrate the potential of an intensified, integrated process for particle attribute engineering.

Main Methods:

• Utilized a seeded cooling crystallization process integrated with a wet mill unit.
• Employed interchangeable rotor-tooth configurations for size control.
• Incorporated inline focused beam reflectance measurement (FBRM) and particle vision measurement (PVM).
• Applied a computational tool to convert chord length distribution (CLD) to particle size distribution (PSD).

Main Results:

• Demonstrated significant control over acetaminophen particle size and shape through optimized wet milling and crystallization.
• Observed consistent surface energies across a range of engineered particle sizes.
• Quantified the interplay between size reduction and growth mechanisms via FBRM and computational analysis.

Conclusions:

• The integrated wet milling crystallization platform enables precise engineering of acetaminophen particle attributes.
• Consistent surface energies achieved highlight the process's potential for tailored particle design.
• This intensified crystallization approach offers a pathway to desirable, reproducible particle properties.