Removal of API's (Active Pharmaceutical Ingredients) from Organic Solvents by Nanofiltration

Abstract

The removal of 5 specific active pharmaceutical ingredients (API's) with molecular weight of 189, 313, 435, 531, and 721, respectively, from toluene, methylene chloride, and methanol was studied by using solvent resistant nanofiltration. Three membranes of the StarMem series (120, 122, and 228), with cut-off values of 200, 220, and 280 respectively, were used in the experiments. Although the rejections expected from the size difference between solutes and membrane pores are high, the results largely depended on the solvent used. For toluene, rejections were rather small, due to the low molecular weight of the solutes of interest (all API's except for the largest compound). Modelling of the rejection curve showed that the minimum molecular weight of a solute to obtain a rejection of 90% in toluene with the membranes used, is ca. 600. The application in methylene chloride was unsuccessful due to partial dissolution of the membrane top layer; other polymeric membranes such as the Solsep series might be more successful. The rejections in methanol were sufficiently high (.90%) to allow implementation: the rejection can be significantly increased by using a module design with double membrane passage and recirculation of the retentate, as was calculated from mass balances. A comparison of a (single pass) nanofiltration system with a throughput distillation unit, currently in use, showed that the energy consumption is 200 times lower in the nanofiltration system.

Recent Advances in Polymeric Solvent‐Resistant Nanofiltration Membranes

“…A distillation process that recovers 451 tons of methanol annually consumes 162 MWh, which is over 200 times higher than that the energy consumption of the SRNF separation process. 169 A similar conclusion was made by Rundquist et al, 170 which indicated that SRNF showed significant potentials for recovering used solvents in the API crystallization process because of its lower energy consumption compared with that of the conventional distillation. Other reports have focused on pharmaceutical purification processes by combining SRNF with other separation techniques, such as counter-current chromatography.…”

“…175 the same authors detailed the design of a two-stage membrane process to completely recover API from methanol. 169 In this system, the actual rejection is 91% with an 80% of recovery rate and 83% observed rejection. The continuous separation process yields only 1.7 ppm of API in the permeate solution.…”

“…Sheth et al 165 claimed that precompacting commercial MPF-50 or MPF-60 with used solvents at operational pressures and temperatures is necessary to remove erythromycin because precompaction increased the rejection of erythromycin by SRNF membranes, which reduced the loss of erythromycin and increased the purification efficiency. Shi et al 166 fabricated a type of PI membrane to concentrate spiramycin 220 (n-alkanes in toluene) [168][169][170][171][173][174][175]180,182,184,[190][191][192]195,197 Starmem TM 228 280 (n-alkanes in toluene) 169,179,184,196 Starmem TM 240 400 (n-alkanes in toluene) [171][172][173][174][175]180,182,184,185,189,196,197 Puramem TM extracts and recover the used solvent (butyl acetate). They indicated that the permeability of the spiramycin solution was significantly affected by the operating conditions, although the rejection of spiramycin (higher than 99%) was not influenced.…”

Separation of a high-value pharmaceutical compound from waste ethanol by nanofiltration

“…Separation processes are extremely important in the chemical and pharmaceutical industry since about 50-90% of capital investments in the chemical industry are related to separation processes [1]. In addition, synthesis of active pharmaceutical ingredients (APIs) in the pharmaceutical industry is often carried out in organic solvents and involves the separation of products with high added value from the solvent.…”

Preparation and characterization of a positively charged nanofiltration membrane based on poly(arylene ether sulfone) with tertiary amine groups

“…All the advantages of nanofiltration are due to the nanometersized pores and electrical charges on the selective layer. Nanofiltration membranes have wide applications such as water softening, removal of dyes, pesticides and natural organic matter from drinking water, recovery of valuable pharmaceutical products, and removal heavy metal ion from industrial wastewater [2][3][4][5][6][7].…”