Controlled production of the elusive metastable form II of acetaminophen (paracetamol): a fully scalable templating approach in a cooling environment

Lauren R Agnew; Dyanne L Cruickshank; Thomas McGlone; Chick C Wilson

doi:10.1039/c6cc01032f

Controlled production of the elusive metastable form II of acetaminophen (paracetamol): a fully scalable templating approach in a cooling environment

Chem Commun (Camb). 2016 May 31;52(46):7368-71. doi: 10.1039/c6cc01032f.

Authors

Lauren R Agnew¹, Dyanne L Cruickshank², Thomas McGlone³, Chick C Wilson¹

Affiliations

¹ EPSRC Centre for Innovative Manufacturing in Continuous Manufacturing and Crystallisation, University of Bath, Bath, BA2 7AY, UK. C.C.Wilson@bath.ac.uk and Department of Chemistry, University of Bath, Bath, BA2 7AY, UK.
² Department of Chemistry, University of Cape Town, Rondebosch, 7701, South Africa.
³ EPSRC Centre for Innovative Manufacturing in Continuous Manufacturing and Crystallisation, c/o Strathclyde Institute for Pharmacy and Biomedical Sciences, Technology and Innovation Centre, 99 George Street, Glasgow, G1 1RD, UK.

PMID: 26926388
DOI: 10.1039/c6cc01032f

Abstract

A scalable, transferable, cooling crystallisation route to the elusive, metastable, form II of the API acetaminophen (paracetamol) has been developed using a multicomponent "templating" approach, delivering 100% polymorphic phase pure form II at scales up to 120 g. Favourable solubility and stability properties are found for the form II samples.