TY - JOUR
T1 - Continuous Crystallization of Paracetamol (Acetaminophen) Form II
T2 - Selective Access to a Metastable Solid Form
AU - Agnew, Lauren R.
AU - McGlone, Thomas
AU - Wheatcroft, Helen P.
AU - Robertson, Amy
AU - Parsons, Anna R.
AU - Wilson, Chick C.
PY - 2017/5/3
Y1 - 2017/5/3
N2 - The first continuous crystallization of a metastable polymorphic form of an active pharmaceutical ingredient is reported. Paracetamol form II, which displays enhanced solubility and compressibility in comparison to the stable form I, has been successfully crystallized in two continuous platforms: a continuous oscillatory baffled crystallizer and a mixed suspension mixed product removal (MSMPR) system, in the presence of the structurally similar molecule metacetamol as a template molecule. Samples from both crystallizers display high polymorphic purity and high solid phase purity, with the samples from the MSMPR in particular showing no evidence of the presence of a residual template molecule. The crystallization was found to be rapidly transferrable between the two continuous platforms. Samples produced display good stability with respect to the known form II to form I transition, reflecting the polymorphic selectivity achieved.
AB - The first continuous crystallization of a metastable polymorphic form of an active pharmaceutical ingredient is reported. Paracetamol form II, which displays enhanced solubility and compressibility in comparison to the stable form I, has been successfully crystallized in two continuous platforms: a continuous oscillatory baffled crystallizer and a mixed suspension mixed product removal (MSMPR) system, in the presence of the structurally similar molecule metacetamol as a template molecule. Samples from both crystallizers display high polymorphic purity and high solid phase purity, with the samples from the MSMPR in particular showing no evidence of the presence of a residual template molecule. The crystallization was found to be rapidly transferrable between the two continuous platforms. Samples produced display good stability with respect to the known form II to form I transition, reflecting the polymorphic selectivity achieved.
UR - http://www.scopus.com/inward/record.url?scp=85018976683&partnerID=8YFLogxK
UR - http://dx.doi.org/10.1021/acs.cgd.6b01831
U2 - 10.1021/acs.cgd.6b01831
DO - 10.1021/acs.cgd.6b01831
M3 - Article
AN - SCOPUS:85018976683
VL - 17
SP - 2418
EP - 2427
JO - Crystal Growth and Design
JF - Crystal Growth and Design
SN - 1528-7483
IS - 5
ER -