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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

Visualization of the molecular arrangement withinthe crystal structuresof paracetamol form I,21 II,21 and III11 togetherwith the contact plane with respect of the SiOx surface. The table below summarizes the used crystal latticeparameters with their corresponding CSD code, space group, and correspondingtemperature at which the experiments were performed.
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fig2: Visualization of the molecular arrangement withinthe crystal structuresof paracetamol form I,21 II,21 and III11 togetherwith the contact plane with respect of the SiOx surface. The table below summarizes the used crystal latticeparameters with their corresponding CSD code, space group, and correspondingtemperature at which the experiments were performed.

Mentions: GIXD measurementsof the three samples are shown in Figure 1.The GIXD measurement in general allows netplaneswhich are close to the surface-normal to be detected within thickfilms19 (up to hundreds of nanometers fororganic layers) as well as within thin films consisting of a monolayer.20 High intensity spots correspond to Bragg reflectionswhich can be used to index the pattern and thus to identify theircrystal structures. The measurements of the sample containing formI reveal ring-like Bragg reflections showing that the crystallitesarrange like a random oriented powder; i.e., no preferred orientationis observed. The indexation shows that all rings are a result of paracetamolbeing in the thermodynamic stable polymorph form I with a monoclinicunit cell (Figure 2). The GIXD pattern of formII shows defined spots at qz = 0.0, 0.8, 1.7 nm–1 and various qxy. The indexation revealsthat these spots are a result of paracetamol being in form II conformationwith an orthorhombic unit cell. In addition, the crystallites of formII show a preferred orientation with respect to the surface, wherebythe 001 plane is in contact with the surface. However, rings are alsopresent within the pattern indicating random oriented form I domains.This shows that the sample contains two polymorphs simultaneously,even if the amount of form I is very low compared to form II. Theform III sample reveals a GIXD pattern with spots being distinct fromthe previously observed ones. The indexation of the spots can be achievedby introducing a 021 contact plane with respect to the surface withan orthorhombic unit cell (compare Figure 2). The smearing of the Bragg spots shows that the mosaicity of thecrystalline needles is relatively high. This means that the moleculeshave a certain degree of freedom to assemble at the silica surfacewhich is different compared to form II with a nearly perfect alignment.


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

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

Visualization of the molecular arrangement withinthe crystal structuresof paracetamol form I,21 II,21 and III11 togetherwith the contact plane with respect of the SiOx surface. The table below summarizes the used crystal latticeparameters with their corresponding CSD code, space group, and correspondingtemperature at which the experiments were performed.
© Copyright Policy
Related In: Results  -  Collection

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

fig2: Visualization of the molecular arrangement withinthe crystal structuresof paracetamol form I,21 II,21 and III11 togetherwith the contact plane with respect of the SiOx surface. The table below summarizes the used crystal latticeparameters with their corresponding CSD code, space group, and correspondingtemperature at which the experiments were performed.
Mentions: GIXD measurementsof the three samples are shown in Figure 1.The GIXD measurement in general allows netplaneswhich are close to the surface-normal to be detected within thickfilms19 (up to hundreds of nanometers fororganic layers) as well as within thin films consisting of a monolayer.20 High intensity spots correspond to Bragg reflectionswhich can be used to index the pattern and thus to identify theircrystal structures. The measurements of the sample containing formI reveal ring-like Bragg reflections showing that the crystallitesarrange like a random oriented powder; i.e., no preferred orientationis observed. The indexation shows that all rings are a result of paracetamolbeing in the thermodynamic stable polymorph form I with a monoclinicunit cell (Figure 2). The GIXD pattern of formII shows defined spots at qz = 0.0, 0.8, 1.7 nm–1 and various qxy. The indexation revealsthat these spots are a result of paracetamol being in form II conformationwith an orthorhombic unit cell. In addition, the crystallites of formII show a preferred orientation with respect to the surface, wherebythe 001 plane is in contact with the surface. However, rings are alsopresent within the pattern indicating random oriented form I domains.This shows that the sample contains two polymorphs simultaneously,even if the amount of form I is very low compared to form II. Theform III sample reveals a GIXD pattern with spots being distinct fromthe previously observed ones. The indexation of the spots can be achievedby introducing a 021 contact plane with respect to the surface withan orthorhombic unit cell (compare Figure 2). The smearing of the Bragg spots shows that the mosaicity of thecrystalline needles is relatively high. This means that the moleculeshave a certain degree of freedom to assemble at the silica surfacewhich is different compared to form II with a nearly perfect alignment.

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