Continuous Manufacturing of Cocrystals Using 3D-Printed Microfluidic Chips Coupled with Spray Coating
Aytug Kara1, Dinesh Kumar2, Anne Marie Healy3
1Departament of Pharmaceutics and Food Science, School of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain.
Pharmaceuticals (Basel, Switzerland)
|August 26, 2023
Summary
3D-printed microfluidic chips enable precise control over cocrystal formation, yielding high-purity sulfadimidine:4-aminosalicylic acid cocrystals with desirable morphology. This technology facilitates continuous manufacturing for improved pharmaceutical formulations.
Area of Science:
- Pharmaceutical Science
- Materials Science
- Chemical Engineering
Background:
- Cocrystals offer a strategy to enhance the physicochemical properties of active pharmaceutical ingredients (APIs).
- Controlling particle size and morphology is crucial for cocrystal medicinal products, as needle-shaped crystals pose manufacturing challenges.
- Advanced methods are needed for high-purity cocrystal engineering with improved solubility, bioavailability, and optimal crystal habits.
Purpose of the Study:
- To utilize 3D-printed microfluidic chips for controlling the habit and polymorphism of sulfadimidine (SDM): 4-aminosalicylic acid (4ASA) cocrystals.
- To investigate the role of polyvinylpyrrolidone (PVP) in cocrystal formation and morphology control.
- To establish a continuous manufacturing process for SDM:4ASA cocrystals.
Main Methods:
- Fabrication of 3D-printed microfluidic chips for cocrystal synthesis.
- Mixing of SDM and 4ASA in the presence of PVP within microfluidic channels.
- Comparison of microscale mixing in microfluidic devices versus macroscale mixing.
- Integration of the microfluidic chip with a fluidized bed for continuous manufacturing.
Main Results:
- Microfluidic mixing with PVP yielded high-purity SDM:4ASA cocrystals, inhibiting needle-shaped crystal growth.
- Macroscale mixing with PVP failed to control crystal habit and resulted in impurities.
- Microfluidic devices enabled homogenous and rapid mixing due to high surface-to-volume ratios and controlled flow rates.
- Continuous manufacturing of SDM:4ASA cocrystals coated on beads was achieved in a single step.
Conclusions:
- 3D-printed microfluidic technology provides effective control over cocrystal habit and polymorphism.
- Microfluidic systems offer superior mixing efficiency compared to macroscale methods for cocrystal preparation.
- Continuous manufacturing integration enables efficient, single-step cocrystal formulation generation.
Keywords:
3D printing4-aminosalicylic acidSLAchipscocrystalcontinuous manufacturingcrystal habitfluidized bedmicrofluidicsspray coatingsulfadimidine
