From discovery to scale-up: alpha-lipoic acid : nicotinamide co-crystals in a continuous oscillatory baffled crystalliser

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Zhao, Lihua and Raval, Vishal and Briggs, Naomi E. B. and Bhardwaj, Rajni M. and McGlone, Thomas and Oswald, Iain D. H. and Florence, Alastair J. (2014) From discovery to scale-up: alpha-lipoic acid : nicotinamide co-crystals in a continuous oscillatory baffled crystalliser. CrystEngComm, 16 (26). pp. 5769-5780. ISSN 1466-8033 (https://doi.org/10.1039/c4ce00154k)

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Abstract

The crystalline nutritional supplement alpha-lipoic acid degrades rapidly on exposure to temperatures above its melting point 65 degrees C and to light. A small-scale experimental co-crystal screen has produced three novel co-crystals of alpha-lipoic acid that each display enhanced thermal stability and differences in aqueous solubilities compared to alpha-lipoic acid. In each case, the initial screening procedure produced tens of milligrams of material enabling initial identification, characterisation and crystal structure determination. The structure of the alpha-lipoic acid : nicotinamide co-crystal was determined by single crystal X-ray diffraction and used for subsequent phase identification. Scale-up of the co-crystallisation process of alpha-lipoic acid with nicotinamide was then investigated in a continuous oscillatory baffled crystalliser. Over 1 kg of solid co-crystals was produced using a continuous crystallisation process in a continuous oscillatory baffled crystalliser at a throughput of 350 g h-1 yielding a purity of 99% demonstrating this as an effective route to rapid scale-up of a novel co-crystal system.

ORCID iDs

Zhao, Lihua, Raval, Vishal ORCID logoORCID: https://orcid.org/0000-0002-0620-3525, Briggs, Naomi E. B., Bhardwaj, Rajni M., McGlone, Thomas ORCID logoORCID: https://orcid.org/0000-0002-9897-1790, Oswald, Iain D. H. ORCID logoORCID: https://orcid.org/0000-0003-4339-9392 and Florence, Alastair J. ORCID logoORCID: https://orcid.org/0000-0002-9706-8364;
CORE (COnnecting REpositories)