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Published on: June 20, 2019
Agglomerative crystallization of ABT-510 in a partially miscible solvent system
Ahmad Y Sheikh1, Agnes Pal, Shekhar Viswanath
1Global Pharmaceutical R&D, Abbott Labs, North Chicago, IL, USA. ahmad.sheikh@abbott.com
Journal of Pharmaceutical Sciences
|August 9, 2007
Summary
This study introduces a novel agglomerative crystallization method for nonapeptide (ABT-510) processing. The technique uses partial solvent miscibility to create an in-situ wetting agent, improving needle-like crystal handling and promoting rapid crystal form conversion.
Area of Science:
- Chemical Engineering
- Crystallization Science
- Pharmaceutical Manufacturing
Background:
- Needle-like crystals, such as those of nonapeptide ABT-510, present processing challenges.
- Traditional crystallization methods may not adequately address particle morphology issues.
- Improving crystal habit is crucial for efficient downstream processing and formulation.
Purpose of the Study:
- To develop and demonstrate a modified wet agglomeration technique for improved processing of needle-like crystals.
- To utilize partial miscibility in solvent systems for in-situ wetting agent generation.
- To optimize particle shape and crystal form conversion during crystallization.
Main Methods:
- Developed an agglomerative crystallization process leveraging partial miscibility of solvent systems.
- Generated an in-situ wetting agent by exploiting phase separation (1-5%) within the solvent system.
- Investigated solid-liquid and liquid-liquid equilibria to establish optimal process trajectories and wetting agent properties.
- Optimized antisolvent addition profiles and scaled up the process using Process Analytical Technology (PAT).
Main Results:
- Achieved effective agglomeration of needle-like crystals using the in-situ generated wetting agent.
- Demonstrated control over agglomerative particle shape by modifying process trajectories.
- Observed extremely rapid crystal form conversion to the desired form near the biphasic solvent region.
- Successfully scaled up the optimized agglomerative crystallization process with consistent performance.
Conclusions:
- The developed agglomerative crystallization process effectively improves the handling of challenging crystal morphologies.
- In-situ wetting agent generation via controlled phase separation offers a versatile approach to particle engineering.
- The process facilitates rapid and efficient conversion to the desired crystalline form, crucial for pharmaceutical applications.
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