Continuous Membrane-Assisted Crystallization To Increase the Attainable Product Quality of Pharmaceuticals and Design Space for Operation

Continuous manufacturing is an important paradigm shift in pharmaceutical industries and has renewed the interest in continuous crystallization. The combination of crystallization and membranes is a promising hybrid technology for separation and purification of pharmaceuticals. The impact of membranes as an extension to conventional continuous crystallization processes on attainable product quality and design space is investigated systematically using model-based optimization. The proposed model is based on a full population balance such that all relevant crystallization phenomena can be included and is solved using a first-order discretization scheme with a hybrid grid. A case study involving continuous crystallization of paracetamol using a series of mixed suspension, mixed product removal (MSMPR) crystallizers is presented to illustrate the approach. The results show that the attainable size and design space can be enlarged significantly by extending conventional crystallization with membranes. In particular, larger crystals or shorter residence times can be achieved. Furthermore, to obtain a crystal size within a desired range, a broader range of temperatures can be applied, which increases operational flexibility

Additional file 1: Figure S1. of Synthesis of ZnO/Si Hierarchical Nanowire Arrays for Photocatalyst Application

High resolution XPS spectra of ZnO/Si nanowire arrays before and after photocatalysis. (a1–a3) Deconvolution of C (1s), O (1s), and Zn (2p) core levels in sample ALD before photocatalysis. (b1–b3) Deconvolution of C (1s), O (1s), and Zn (2p) core levels in sample ALD after photocatalysis. (c1–c3) Deconvolution of C (1s), O (1s), and Zn (2p) core levels in sample MS before photocatalysis. (d1–d3) Deconvolution of C (1s), O (1s), and Zn (2p) core levels in sample MS after photocatalysis. Figure S2. Spectral intensity of different bonds after photocatalysis (I) in contrast to that of before photocatalysis (I0) for sample ALD and sample MS as calculated from the deconvoluted spectra in Figure S1. (i) C-C bond, (ii) C-O-Zn bond, (iii) O-Zn bond, (iv) O-H bond or oxygen vacancies, (v) Zn 2p3/2, and (vi) Zn 2p1/2. (DOC 307 kb