Synthesis and optimization of wide pore superficially porous particles by a one-step coating process for separation of proteins and monoclonal antibodies

Superficially porous particles (SPPs) with pore size ranging from 90A to 120A have been a great success for the fast separation of small molecules over totally porous particles in recent years. However, for the separation of large biomolecules such as proteins, particles with large pore size (e.g. >= 300 angstrom) are needed to allow unrestricted diffusion inside the pores. One early example is the commercial wide pore (300 angstrom) SPPs in 5 mu m size introduced in 2001. More recently, wide pore SPPs (200 angstrom and 400 angstrom) in smaller particle sizes (3.5-3.6 mu m) have been developed to meet the need of increasing interest in doing faster analysis of larger therapeutic molecules by biopharmaceutical companies. Those SSPs in the market are mostly synthesized by the laborious layer-by-layer (LBL) method. A one step coating approach would be highly advantageous, offering potential benefits on process time, easier quality control, materials cost, and process simplicity for facile scale-up. A unique one-step coating process for the synthesis of SPPs called the "coacervation method" was developed by Chen and Wei as an improved and optimized process, and has been successfully applied to synthesis of a commercial product, Poroshell 120 particles, for small molecule separation. In this report, we would like to report on the most recent development of the one step coating coac ervation method for the synthesis of a series of wide pore SPPs of different particle size, pore size, and shell thickness. The one step coating coacervation method was proven to be a universal method to synthesize SPPs of any particle size and pore size. The effects of pore size (300 angstrom vs. 450 angstrom), shell thickness (0.25 mu m vs. 0.50 mu m), and particle size (2.7 mu m and 3.5 mu m) on the separation of large proteins, intact and fragmented monoclonal antibodies (mAbs) were studied. Van Deemter studies using proteins were also conducted to compare the mass transfer properties of these particles. It was found that the larger pore size actually had more impact on the performance of mAbs than particle size and shell thickness. The SPPs with larger 3.5 pin particle size and larger 450 angstrom pore size showed the best resolution of mAbs and the lowest back pressure. To the best of our knowledge, this is the largest pore size made on SPPs. These results led to the optimal particle design with a particle size of 3.5 mu m, a thin shell of 0.25 mu m and a larger pore size of 450 angstrom. (C) 2015 Elsevier B.V. All rights reserved.