Increasing the Batch Size of a QESD Crystallization by Using a MSMPR Crystallizer

Area of Science:

• Pharmaceutical Sciences
• Chemical Engineering
• Materials Science

Background:

• Quasi-emulsion solvent diffusion (QESD) crystallization improves drug and excipient micromeritic properties by forming spherical, hollow particles.
• Batch QESD crystallization faces challenges with decreasing particle size as solvent fraction increases, necessitating multiple runs.
• Scaling up batch QESD processes is time- and material-intensive due to repeated operations.

Purpose of the Study:

• To adapt a lab-scale batch QESD crystallizer into a continuous mixed-suspension, mixed-product removal (MSMPR) system.
• To investigate the feasibility of increasing batch size in QESD crystallization by extending system run time.
• To evaluate the impact of mean residence time (MRT) on particle size distribution and flowability in continuous QESD.

Main Methods:

• Conversion of a lab-scale batch crystallizer to an MSMPR configuration.
• Prediction and experimental verification of mean residence time (MRT) and solvent fraction.
• Crystallization of metformin hydrochloride using the modified QESD process.

Main Results:

• Successful crystallization of over 50 g of metformin hydrochloride in a single continuous run.
• Maintained good flowability of the crystallized product without significant particle size variation.
• Validated the effect of MRT on particle size distribution at a larger scale than previously reported.

Conclusions:

• The MSMPR system effectively scales up QESD crystallization for improved process efficiency.
• Continuous QESD crystallization offers a viable method for producing metformin hydrochloride with desirable particle characteristics.
• The study demonstrates the successful application of continuous crystallization principles to enhance QESD processes.