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

Lihua Zhao, Vishal Raval, Naomi E. B. Briggs, Rajni M. Bhardwaj, Thomas McGlone, Iain D. H. Oswald, Alastair J. Florence

Research output: Contribution to journalArticle

38 Citations (Scopus)

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.
LanguageEnglish
Pages5769-5780
Number of pages12
JournalCrystEngComm
Volume16
Issue number26
Early online date4 Mar 2014
DOIs
Publication statusPublished - 14 Jul 2014

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lipoic acid
Thioctic Acid
nicotinamide
Niacinamide
Crystals
Acids
crystals
Crystallization
crystallization
supplements
melting points
Melting point
Screening
purity
Thermodynamic stability
thermal stability
screening
solubility
Solubility
Crystal structure

Keywords

  • crystal X-ray diffraction
  • co-crystallisation process
  • crystal structure determination

Cite this

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title = "From discovery to scale-up: alpha-lipoic acid: nicotinamide co-crystals in a continuous oscillatory baffled crystalliser",
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.",
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From discovery to scale-up: alpha-lipoic acid : nicotinamide co-crystals in a continuous oscillatory baffled crystalliser. / Zhao, Lihua; Raval, Vishal; Briggs, Naomi E. B.; Bhardwaj, Rajni M.; McGlone, Thomas; Oswald, Iain D. H.; Florence, Alastair J.

In: CrystEngComm, Vol. 16, No. 26, 14.07.2014, p. 5769-5780.

Research output: Contribution to journalArticle

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