iBB

Lupanine is used as a building block in the synthesis of sparteine, a chiral selector in drug synthesis. This alkaloid is found in wastewaters derived from the debittering process that makes lupin beans edible. In a recently published work, carried out by researchers of the Faculty of Sciences and Faculty of Pharmacy from the University of Lisbon, and Teresa Esteves, Frederico Ferreira, Flávio Ferreira and Ana Mota from BERG-iBB, a computational chemistry approach was taken to design molecularly imprinted polymers (MIPs) selecting itaconic acid, a biobased building block, as a functional monomer that can provide higher affinities for lupanine. In this work, lupanine was concentrated from lupin bean wastewater by nanofiltration, extracted with ethyl acetate, and purified using the synthesized MIP, which was able to selectively recognize lupanine and improve its purity to 88%, with 82% recovery of the alkaloid, showing the potential application of this strategy to render the industrial process more sustainable.

A detailed investigation on the assessment of commercial resins for genotoxins removal in organic solvent solutions has just been published by Teresa Esteves, Flávio Ferreira and Frederico Ferreira from BERG-iBB, in collaboration with Hovione. The study addresses mitigation of active pharmaceutical ingredient (API) loss during purification in recrystallization mother liquors by including a resin adsorption step to remove potential genotoxin impurities (PGTIs). Two resins were identified, AG 50W-X2 and IRA68, to efficiently remove an aromatic amine (4-dimethylaminopyridine) and a sulfonate ester (methyl p-toluenesulfonate) from methanol solutions, respectively, with adsorptions higher than 98% and an API loss lower than 10% using these resins combined in a single adsorption step. The potential for improving the API recrystallization economics, through mitigation of API losses is also suggested. Mometasone furoate (Meta) was used as model active pharmaceutical ingredient (API) in the presence of 4-dimethylaminopyridine (DMAP) and methyl p-toluenesulfonate (MPTS) as two model PGTIs. The work was published in the journal Separation Science and Technology.

Removal of genotoxic impurities (GTI) from active pharmaceutical ingredients (API) is mandatory to deliver safe medicines, but to achieve GTI at ultra-low limit (<1.5 µg/day) implies significative API loss. A recent paper published in the journal Membranes by Flávio Ferreira, Leonor Resina, Teresa Esteves and Frederico Ferreira from BERG-iBB, propose the use of a mathematical model to predict whether adsorption or membrane process is suitable for API purification. Moreover, in cases where none of them have an acceptable API loss, a hybrid process combining both processes was developed, reducing API loss from 24.76% to 9.76%. Furthermore, economic and environmental analyses were also performed.