title: Synthesis of Caffeine/Maleic Acid Co-crystal by Ultrasound-assisted Slurry Co-crystallization.
abstract: A green approach has been used for co-crystallization of noncongruent co-crystal pair of caffeine/maleic acid using water. Ultrasound is known to affect crystallization; hence, the effect of high power ultrasound on the ternary phase diagram has been investigated in detail using a slurry co-crystallization approach. A systematic investigation was performed to understand how the accelerated conditions during ultrasound-assisted co-crystallization will affect different regions of the ternary phase diagram. Application of ultrasound showed considerable effect on the ternary phase diagram, principally on caffeine/maleic acid 2:1 (disappeared) and 1:1 co-crystal (narrowed) regions. Also, the stability regions for pure caffeine and maleic acid in water were narrowed in the presence of ultrasound, expanding the solution region. The observed effect of ultrasound on the phase diagram was correlated with solubility of caffeine and maleic acid and stability of co-crystal forms in water.
authors.affiliation: Centre for Pharmaceutical Engineering Science, University of Bradford, Bradford, West Yorkshire, UK.
authors.forename: Prafulla P
authors.initials: PP
authors.lastname: Apshingekar
authors.affiliation: Centre for Pharmaceutical Engineering Science, University of Bradford, Bradford, West Yorkshire, UK.
authors.forename: Suyog
authors.initials: S
authors.lastname: Aher
authors.affiliation: Centre for Pharmaceutical Engineering Science, University of Bradford, Bradford, West Yorkshire, UK; IRC in Polymer Science and Technology, University of Bradford, Bradford, West Yorkshire, UK.
authors.forename: Adrian L
authors.initials: AL
authors.lastname: Kelly
authors.affiliation: IRC in Polymer Science and Technology, University of Bradford, Bradford, West Yorkshire, UK.
authors.forename: Elaine C
authors.initials: EC
authors.lastname: Brown
authors.affiliation: Centre for Pharmaceutical Engineering Science, University of Bradford, Bradford, West Yorkshire, UK. Electronic address: A.Paradkar1@bradford.ac.uk.
authors.forename: Anant
authors.initials: A
authors.lastname: Paradkar
mesh_terms: D002110:Caffeine / Q000138:chemical synthesis / Q000737:chemistry*; D003460:Crystallization / Q000379:methods*; D055772:Green Chemistry Technology / Q000379:methods; D008298:Maleates / Q000138:chemical synthesis / Q000737:chemistry*; D044367:Phase Transition; D012995:Solubility; D013010:Sonication / Q000379:methods*; D014867:Water / Q000737:chemistry
chemical_list: D008298:Maleates; D014867:Water; D002110:Caffeine; C030272:maleic acid
keywords: co-crystals; crystallization; phase diagram; solubility; stability; supersaturation; ultrasound