Scaling up Metal Scavenging Operations for Pharmaceutical Pilot Plant Manufactures

Abstract

Functionalised silicas, used for selectively removing metal impurities in process streams, are packed in cartridges and inserted into multicartridge filters. The scavenging step that follows a catalytic reaction involves the single pass of the process stream through the multicartridge filter setup at a predetermined linear velocity and temperature. Efficiency in metal reduction as high as 98% has been so far achieved at tens of kilograms scale. Furthermore, the precious metal anchored onto the scavenger’s functionalities can be recovered and refined. Our chronological development of a versatile, general, and easily scalable format for metal scavenging at process scales is described, illustrated by application in real time to a range of projects passing through our Pharmaceutical Pilot Plant, employing a variety of metals (palladium, rhodium, iridium). Benefits of the cartridge format in terms of economics and environmental impact are also initially assessed.

Towards a quantitative understanding of palladium metal scavenger performance: an electronic structure calculation approach

“…2). These metal sets represent Pd(II) in different ligand environments (6 and 7) and Pd(0) in a model chelated bis-phosphine environment (8). Ligand 9 is the simplest thiol ligand relevant to the fuller ligand set (vide infra).…”

“…3. The Pd(II) system has d 8 electronic configuration which favours a square planar geometry with an empty d orbital. This empty d orbital (conventionally designated the d x 2 −y 2) offers a path (along x and y axes) for each of four ligands to approach the metal and avoid electron-electron repulsions.…”

“…PhosphonicS has developed and applied a range of successful multifunctionalised materials based on mesoporous silica, which possess siloxane (Si-O-Si) bonds linking organic functionality to the silica framework, for the removal of palladium residues from product streams; 7 some of these have been deployed at scale. 8 Materials based on polystyrene matrices are also available commercially. Sulfur-based organic functional groups which offer potential strong metalligand interactions, and which can be exploited in metal sequestration are privileged in the design of these materials.…”

Palladiumkatalyse im industriellen Einsatz

“…auf Aktivkohlen oder modifizierten Harzen z.B. mit Schwefelfunktionalisierung, die dann zur Aufarbeitung des Edelmetalls verwendet werden können [11].…”

Effective Method To Remove Metal Elements from Pharmaceutical Intermediates with Polychelated Resin Scavenger

“…5 Astra Zeneca group has conducted the operations for pharmaceutical pilot plant manufactures to remove a variety of metals including palladium, rhodium and iridium using silica based adsorbent. 6 Notable advantage of these methodologies is that the separation of scavenger is a straightforward by filtration or can be used in the fixed-bed adsorbent. These scavenging operations are more efficient in a volumetric productivity and can avoid the product loss as low as possible in comparison with the recrystallization.…”