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Expanding Beyond Water-Based Percrystallization: Assessment of Active Pharmaceutical Ingredients Processing and
Catarina B Sequeira1,2, João C Diniz da Costa1,3, António Henriques2
1LAQV-REQUIMTE, Department of Chemistry, NOVA School of Science and Technology, NOVA University Lisbon, 2829-516 Caparica, Portugal.
ACS Omega
|June 22, 2026
Summary
Percrystallization (PerX) offers a continuous, single-step alternative for manufacturing Active Pharmaceutical Ingredients (APIs) using solvents. This membrane technology achieves high yields and purity while producing crystals with superior properties.
Area of Science:
- Chemical Engineering
- Materials Science
- Pharmaceutical Manufacturing
Background:
- Traditional Active Pharmaceutical Ingredient (API) manufacturing involves energy-intensive, multi-step batch processes like crystallization, filtration, and drying.
- These conventional methods often result in solvent inefficiency, product loss, contamination risks, and inconsistent particle characteristics.
Purpose of the Study:
- To investigate the feasibility of Percrystallization (PerX), a membrane crystallization technology, for solvent-based API production.
- To evaluate the performance of different membranes and solvents relevant to pharmaceutical manufacturing.
Main Methods:
- Utilized α-alumina and modified carbon-coated membranes for PerX experiments with various organic solvents.
- Analyzed membrane wettability, solvent flux, and crystallization performance for ibuprofen in ethanol, methanol, acetone, and acetonitrile.
- Assessed crystal purity, yield, morphology, and residual solvent levels.
Main Results:
- The α-alumina membrane demonstrated superior performance due to better wettability in solvent systems.
- PerX successfully crystallized ibuprofen in multiple solvents, achieving high yields (>95%) and purity (>99.9%).
- PerX-produced crystals exhibited a plate-like morphology with enhanced mechanical properties compared to commercial ibuprofen.
Conclusions:
- Percrystallization is a viable single-step technology for solvent-based API crystallization, offering integrated drying and solvent recovery.
- This method reduces process complexity and downstream processing demands for continuous pharmaceutical manufacturing.
- PerX technology holds significant potential for improving API production efficiency and product quality.
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