Process scale crystallization is important in the production of nearly 90% of all active pharmaceutical ingredients. Continuous plug flow crystallization is an alternative to batch techniques and gives benefits including a profoundly reduced footprint and superior generation of 1-100 µm crystals in a narrow size distribution. Continuous flow antisolvent crystallization generates high supersaturation ratios to initiate crystal nucleation, which can result in system instabilities that affect crystal size properties. DeNovX’s approach is to systematically alter surface energies to facilitate predictable crystal nucleation. Replicate studies using flufenamic acid in ethanol with H<sub>2</sub>O as antisolvent gave 80% of the crystalline material in size ranges that are 55% and 36% narrower at one and four antisolvent injection points, respectively, than the materials obtained from control studies. As a challenge to both continuous flow crystallization and the use of engineered nucleation features, this approach was successfully extended to the synthesis of a cocrystalline material.

Continuous plug flow antisolvent crystallization using surface-energy modified substrates

2019 Spring National Meeting

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