Leveraging Reactive Crystal Spherical Agglomeration to Enable a Scalable and Gelation-Free Manufacturing Process for Medium-Length Fatty Acid Sodium Salts

Reactive crystal spherical agglomeration (CSA) was implemented in a novel process for the manufacture of sodium salts of medium-chain fatty acids (MCFAs). Compounds of this variety are notoriously difficult to isolate using conventional manufacturing methods because of their natural fiber-like crystal morphology, which entrains the solvent matrix and leads to colloidal gelling. The approach described relies on the generation of the MCFA salts via reactive crystallization, while simultaneously confining the developing solids into irregular spheroids using CSA, thus mitigating the colloidal gelation behavior. The resulting process sequence is scalable and transferable, as it can be completed in a single reactor, using readily available commodity reagents and standard manufacturing equipment. The process operates with modest cycle times (3 days, including drying) and with high yields (>90%). Product particle size can be tuned by adjusting the CSA process parameters, enabling control over the output physical characteristics depending on the desired downstream use. Herein, we introduce the challenges surrounding the crystallization of sodium salts of MCFAs, discuss the design of the reactive CSA process─including solvent system selection, reactive crystallization design, and overall parameter optimization─and present examples demonstrating successful implementation at varying scales, including data for the first reported large manufacturing-scale implementation of a CSA process.