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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

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