Continuous Microfluidic Antisolvent Crystallization as a Bottom-Up Solution for the Development of Long-Acting...

Area of Science:

• Pharmaceutical Technology
• Materials Science
• Chemical Engineering

Background:

• Traditional top-down manufacturing methods for long-acting injectables (LAI) face limitations in cost-efficiency and sustainability.
• Tailoring drug characteristics and optimizing manufacturing processes are crucial for developing advanced LAI formulations.

Purpose of the Study:

• To investigate a bottom-up approach using Secoya microfluidic crystallization technology (SCT-CLASC) for producing LAI microsuspensions.
• To compare the SCT-CLASC process with a microchannel reactor-based continuous liquid antisolvent crystallization (MCR-CLASC) setup.
• To optimize the SCT-CLASC process for enhanced drug loading and reduced excipient use in itraconazole (ITZ) microsuspensions.

Main Methods:

• Continuous liquid antisolvent crystallization using SCT-CLASC technology with itraconazole (ITZ) as a model drug.
• Optimization of operating parameters and downstream processing for microsuspension concentration.
• Monitoring of particle size distribution (PSD), solid-state form, and particle morphology for quality control.

Main Results:

• Stable ITZ microsuspensions with a final solid loading of 300 mg ITZ/g suspension were achieved using SCT-CLASC.
• The optimized SCT-CLASC process yielded a post-precipitation feed suspension with 40 mg ITZ/g and a drug-to-excipient ratio of 53:1.
• This represents a significant improvement over the MCR-CLASC setup, which achieved 10 mg ITZ/g and a 2:1 ratio, demonstrating higher drug concentration and lower excipient use.
• Particle characteristics, including PSD (1-10 µm), elongated plate-shaped morphology, and the stable Form I solid-state of ITZ, were maintained.

Conclusions:

• The SCT-CLASC process is a robust, reproducible, and energy-efficient bottom-up approach for manufacturing LAI microsuspensions.
• This technology enables higher drug concentrations and reduced excipient requirements, paving the way for industrial-scale production of ITZ LAI formulations.
• The optimized process ensures the stability and desired solid-state form of the drug within the microsuspensions.