Integrated crystallization, drying, and particle engineering of ibuprofen microcrystals with enhanced flowability...

Area of Science:

• Chemical Engineering
• Crystallization Science
• Pharmaceutical Manufacturing

Background:

• Traditional Active Pharmaceutical Ingredient (API) manufacturing involves sequential crystallization, filtration, and drying steps, which are often bottlenecks.
• Membrane crystallization (PerX) offers an intensified approach by combining solvent removal and crystallization into a single unit operation.

Purpose of the Study:

• To evaluate the efficacy of membrane crystallization (PerX) for ibuprofen crystallization.
• To assess the impact of feed concentration and temperature on PerX performance.
• To characterize the solid-state quality and particle attributes of PerX-produced ibuprofen crystals.

Main Methods:

• Ibuprofen crystallization using membrane percrystallization (PerX) under varying feed concentrations and temperatures.
• Assessment of crystallization yield, flux, solid-state form, purity, and residual solvent content.
• Analysis of particle size distribution, morphology, and powder flowability of the obtained crystals.

Main Results:

• PerX achieved high crystallization yields (>95%) and significant fluxes (up to 5.13 kg API m⁻² memb h⁻¹).
• Ibuprofen was consistently crystallized as the stable Form I with >99.9% purity and low residual solvents and moisture.
• PerX-derived crystals exhibited plate-like morphology, smaller particle sizes (dv50: 3.9–10.2 µm), and enhanced powder flowability compared to commercial ibuprofen.

Conclusions:

• Membrane percrystallization (PerX) effectively integrates crystallization and drying into a single, intensified step for API manufacturing.
• PerX provides precise control over crystal attributes, including solid-state form, purity, and particle characteristics.
• This technology offers a promising alternative to conventional methods, enhancing efficiency and product quality in pharmaceutical production.