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Surface Mediated Structures: Stabilization of Metastable Polymorphs on the Example of Paracetamol.

Ehmann HM, Werzer O - Cryst Growth Des (2014)

Bottom Line: The preparation of typically thermodynamically unstable polymorphic structures is a challenge.Such a preparation technique allows the use of atomic force microscopy and grazing incidence X-ray diffraction measurements revealing detailed information on the morphology and structure of the polymorph.These findings demonstrate a novel approach to provide thermodynamic stability when applied to similar molecules with specific applications.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pharmaceutical Science, Department of Pharmaceutical Technology, Karl-Franzens University of Graz , Universitätsplatz 1, 8010 Graz, Austria.

ABSTRACT
The preparation of typically thermodynamically unstable polymorphic structures is a challenge. However, solid surfaces are well established aids for the formation and stabilization of polymorphic structures within, for instance, organic electronics. In this study, we report the stabilization of a pharmaceutically relevant substance via a solid surface at ambient conditions. Form III of paracetamol, which is typically unstable in the bulk at standard conditions, can be stabilized with a model silica surface by a standard spin coating procedure followed by rapid heat treatment. Such a preparation technique allows the use of atomic force microscopy and grazing incidence X-ray diffraction measurements revealing detailed information on the morphology and structure of the polymorph. Furthermore, the results exhibit that this polymorph is stable over a long period of time revealing surface mediated stabilization. These findings demonstrate a novel approach to provide thermodynamic stability when applied to similar molecules with specific applications.

No MeSH data available.


Related in: MedlinePlus

Atomic force microscopy height images of paracetamolform I, II,and III and the corresponding horizontal texture cuts taken in themiddle of each image (lower right corner).
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fig3: Atomic force microscopy height images of paracetamolform I, II,and III and the corresponding horizontal texture cuts taken in themiddle of each image (lower right corner).

Mentions: In Figure 3 themorphologies of the threesamples containing each polymorph of paracetamol at room temperatureare shown with their corresponding height profiles. The AFM imageof form I reveals the typical shape of monoclinic crystals with prismaticto plate-like morphology, whereby the crystallites are randomly rotatedwith respect to each other. Form II shows a distinct growth morphology,and plate-like structures are present. While the crystal morphologiesare distinct, the height and consequently the coverage are very similarto form I and II, showing that diffusion in the upward direction fromthe surface is negligible. These two observed morphologies fit verywell to previously observed experiments on paracetamol, where morphologicaldifferences are explained by different growth faces being dominant.22 The morphology of form III is distinct fromthe previous two forms, and needle-like structures are present. Thecoverage of the surface is strongly reduced, and consequently theheights of the needle-islands are higher compared to those of formI and II even though the nominal film thickness of the spin coatedsample was very similar. The height of the needles is around 450 nm,which is about three times larger compared to the previous observedheights of form I and II.


Surface Mediated Structures: Stabilization of Metastable Polymorphs on the Example of Paracetamol.

Ehmann HM, Werzer O - Cryst Growth Des (2014)

Atomic force microscopy height images of paracetamolform I, II,and III and the corresponding horizontal texture cuts taken in themiddle of each image (lower right corner).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4125415&req=5

fig3: Atomic force microscopy height images of paracetamolform I, II,and III and the corresponding horizontal texture cuts taken in themiddle of each image (lower right corner).
Mentions: In Figure 3 themorphologies of the threesamples containing each polymorph of paracetamol at room temperatureare shown with their corresponding height profiles. The AFM imageof form I reveals the typical shape of monoclinic crystals with prismaticto plate-like morphology, whereby the crystallites are randomly rotatedwith respect to each other. Form II shows a distinct growth morphology,and plate-like structures are present. While the crystal morphologiesare distinct, the height and consequently the coverage are very similarto form I and II, showing that diffusion in the upward direction fromthe surface is negligible. These two observed morphologies fit verywell to previously observed experiments on paracetamol, where morphologicaldifferences are explained by different growth faces being dominant.22 The morphology of form III is distinct fromthe previous two forms, and needle-like structures are present. Thecoverage of the surface is strongly reduced, and consequently theheights of the needle-islands are higher compared to those of formI and II even though the nominal film thickness of the spin coatedsample was very similar. The height of the needles is around 450 nm,which is about three times larger compared to the previous observedheights of form I and II.

Bottom Line: The preparation of typically thermodynamically unstable polymorphic structures is a challenge.Such a preparation technique allows the use of atomic force microscopy and grazing incidence X-ray diffraction measurements revealing detailed information on the morphology and structure of the polymorph.These findings demonstrate a novel approach to provide thermodynamic stability when applied to similar molecules with specific applications.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pharmaceutical Science, Department of Pharmaceutical Technology, Karl-Franzens University of Graz , Universitätsplatz 1, 8010 Graz, Austria.

ABSTRACT
The preparation of typically thermodynamically unstable polymorphic structures is a challenge. However, solid surfaces are well established aids for the formation and stabilization of polymorphic structures within, for instance, organic electronics. In this study, we report the stabilization of a pharmaceutically relevant substance via a solid surface at ambient conditions. Form III of paracetamol, which is typically unstable in the bulk at standard conditions, can be stabilized with a model silica surface by a standard spin coating procedure followed by rapid heat treatment. Such a preparation technique allows the use of atomic force microscopy and grazing incidence X-ray diffraction measurements revealing detailed information on the morphology and structure of the polymorph. Furthermore, the results exhibit that this polymorph is stable over a long period of time revealing surface mediated stabilization. These findings demonstrate a novel approach to provide thermodynamic stability when applied to similar molecules with specific applications.

No MeSH data available.


Related in: MedlinePlus