Projects per year
Abstract
Investigating crystal nucleation at the nanoscale is of significant interest, in particular as more complex, non-classical routes have roused questions about the classical view of homo- and hetero-nucleation processes. Here, we report the direct observation of a two-step nucleation mechanism during the transformation of anhydrous olanzapine to olanzapine dihydrate. Atomic force microscopy studies of the dominant (100)OZPNI face of olanzapine form I single crystals in contact with water show the formation and growth of dense nanodroplets concentrated around ledge sites. In unstirred solution, apparent ordering and crystallisation from these droplets occurs with olanzapine dihydrate D produced by the templating effect of the underlying olanzapine I lattice. In contrast, under stirred conditions a kinetic dihydrate polymorph, dihydrate B, nucleates probably due to the detachment of nanodroplets from the surface during stirring and a consequent loss of template effect. Computational modelling of the binding of olanzapine growth units on crystal ledges reveals many strongly bound dimer positions unrelated to either crystal structure. This impedes surface integration and contributes to the growth of disordered clusters at the ledge site. Nanocrystal modelling shows that the (100)OZPNI surface favours the nucleation of dihydrate D over the kinetic form. This work gives an important insight into heterogeneous two step nucleation where the first step, the formation of a prenucleation droplet, can in the second step, bifurcate, either to produce the stable form by templating, or the kinetic form on detachment of the nanodroplets.
Original language | English |
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Pages (from-to) | 6382-6393 |
Number of pages | 12 |
Journal | Crystal Growth and Design |
Volume | 17 |
Issue number | 12 |
DOIs | |
Publication status | Published - 23 Oct 2017 |
Keywords
- olanzapine
- hydrates
- two-step nucleation
- templating
- nanocrystals
- ORIENT modelling
- atomic force microscopy
Fingerprint
Dive into the research topics of 'Direct observation of templated two-step nucleation mechanism during olanzapine hydrate formation'. Together they form a unique fingerprint.Profiles
Projects
- 1 Finished
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Computationally Designed Templates for Exquisite Control of Polymorphic Form
Florence, A. (Principal Investigator) & Lamprou, D. (Co-investigator)
EPSRC (Engineering and Physical Sciences Research Council)
1/10/13 → 30/06/18
Project: Research
Research output
- 47 Citations
- 1 Doctoral Thesis
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Nucleation and Growth of Pharmaceutical Crystals
Warzecha, M., 1 Apr 2019, Glasgow: University of Strathclyde. 197 p.Research output: Thesis › Doctoral Thesis
Open AccessFile
Prizes
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Best poster prize at CMAC Summer School on Crystal Nucleation
Warzecha, M. (Recipient), 20 Jun 2016
Prize: Prize (including medals and awards)
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Gold Poster Winner, Scanning Probe Microscopy Conference & User Meeting,
Warzecha, M. (Recipient), 22 Apr 2015
Prize: Prize (including medals and awards)