Volatile Organic Solvents as Osmotic Agents of Organic Solvent Forward Osmosis for Pharmaceutical Concentration

ABSTRACT In the pharmaceutical industry, a preconcentration can reduce the total production cost of active pharmaceutical ingredients (APIs) or their intermediates. For preconcentration, organic solvent forward osmosis (OSFO) is suitable because of its nonthermal nature, low capital cost, and capability for high‐degree concentration. However, OSFO has a drawback where the osmotic agent (OA) can contaminate the concentrated process solution by reverse diffusion. In this study, it was attempted for the first time to use a pure volatile organic solvent as an OA in the OSFO for overcoming the drawback. Because even if the process solution is contaminated, the OA can be removed in the subsequent process (e.g., dry process) of pharmaceutical production. Hydrophobic volatile organic solvents were examined as OAs with a thin film composite membrane with a hydrophilic polyamide selective layer. As a result, it was found that isooctane had the least reverse diffused behavior because of the poorest affinity with the selective layer. Using isooctane in the OSFO experiment, the tocopherol (model API intermediate) concentration increased to 48 wt% with only 0.13 wt% of isooctane contamination. This study clearly reveals the feasibility of the above OA and would open the opportunity for social implementation of OSFO preconcentration in the pharmaceutical industry.