Quantifying Dry Milling in Pharmaceutical Processing: A Review on Experimental and Modeling Approaches

Area of Science:

• Pharmaceutical Engineering
• Materials Science
• Chemical Engineering

Background:

• Particle size reduction is a key pharmaceutical unit operation for enhancing drug properties like solubility and flow.
• Milling processes are complex due to numerous interacting material and process variables, leading to limited understanding.
• Regulatory initiatives, such as the US FDA's focus on quality by design, necessitate better process comprehension.

Purpose of the Study:

• To review process analytical tools for characterizing particle size distribution.
• To examine process modeling tools for simulating particle size reduction.
• To provide an overview of fundamental aspects and experimental/modeling approaches in dry milling.

Main Methods:

• Literature review of process analytical technology (PAT) for particle size analysis.
• Review of computational modeling techniques for milling simulation.
• Synthesis of experimental approaches to quantify milling phenomena.

Main Results:

• Identified key analytical tools for real-time particle size characterization.
• Highlighted the utility of process modeling in predicting and optimizing particle size reduction.
• Summarized fundamental principles governing dry milling physics.

Conclusions:

• Improved understanding of milling requires integrated experimental and modeling strategies.
• Process analytical tools and modeling are essential for quality by design in pharmaceutical manufacturing.
• Further research into the physics of particle fracturing during milling is warranted.