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

Ehmann, Heike; Werzer, Oliver

doi:10.1021/cg500573e

Cited by 43 publications

(72 citation statements)

References 30 publications

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“…Delmas et al Have reported selective crystallization of the orthorhombic form II of PCM using mesoporous silica particles (Delmas et al, ). Similar experiments were also conducted by Ehmann et al with a spin coating of PCM followed by rapid heat treatment in presence of colloidal silica particles (Ehmann & Werzer, ). They have reported crystallization of the polymorphic form III of the PCM which is unstable at ambient conditions.…”

Section: Pharmaceutical Applicationssupporting

confidence: 59%

“…As per general convention, the metastable form should be stable enough to provide biopharmaceutical advantage upto the shelf life of the product (Singhal & Curatolo, 2004 (Delmas et al, 2013). Similar experiments were also conducted by Ehmann et al with a spin coating of PCM followed by rapid heat treatment in presence of colloidal silica particles (Ehmann & Werzer, 2014). They have reported crystallization of the polymorphic form III of the PCM which is unstable at ambient conditions.…”

Section: Metastable Polymorphsmentioning

confidence: 58%

“…Hydrophobic interactions Generation of glycine nanocrystals (Yang & Myerson, 2015) • Oxidized silicon wafers Paracetamol -Crystallization of metastable polymorph III (Ehmann & Werzer, 2014) • Functionalized glass vials Carbamazepine Surface functionality Crystallization of stable and metastable polymorph (Parambil et al, 2014) F I G U R E 4 Application of heteronuclear crystallization process intensification was investigated for different APIs. PCM is one of the most widely consumed medicine which exists in five polymorphic forms (Smith, Bishop, Montgomery, Hamilton, & Vohra, 2014).…”

Section: Glycinementioning

confidence: 99%

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Emerging role of primary heterogeneous nucleation in pharmaceutical crystallization

Thakore

Sood

Bansal

2019

Drug Development Research

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Crystallization is an important and difficult to control unit operation in the pharmaceutical industry. Crystallization can control molecular (i.e., polymorphism) and particulate (i.e., particle size and crystal habit) properties of active pharmaceutical ingredient (API). Moreover, these molecular and particulate properties govern the manufacturability, stability, and biopharmaceutical performance of the API and drug product. Nucleation is a key step and primary heterogeneous nucleation is a common mode of nucleation during crystallization. Hence, it is important to understand the parameters affecting primary heterogeneous nucleation, to achieve desirable properties in crystalline APIs. Primary heterogeneous crystallization has usually been linked to the surface characteristics like topography and functionality of the heteronucleant. The review outlines recent findings in the primary heterogeneous crystallization with specific emphasis on its pharmaceutical applications including regulatory considerations. Molecular‐level mechanisms governing heteronucleation and subsequent outcome in terms of molecular as well as particulate‐level properties of API have also been discussed. Moreover, general guidance for the selection of heteronucleant has also been included. Heterogeneous crystallization is a promising tool for efficient crystallization of API having properties for optimal pharmaceutical performance.

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Section: Pharmaceutical Applicationssupporting

confidence: 59%

Section: Metastable Polymorphsmentioning

confidence: 58%

Section: Glycinementioning

confidence: 99%

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Emerging role of primary heterogeneous nucleation in pharmaceutical crystallization

Thakore

Sood

Bansal

2019

Drug Development Research

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“…The appearance of new polymorphs of a material, if crystallized at a solid substrate surface, can have a significant impact on the physical properties of the material and, therefore, on any potential applications . Such polymorphs, termed as thin‐film, surface‐mediated, or substrate‐induced phases (SIPs), have mostly been observed for organic semiconductors, but could also be of importance for other classes of molecules, such as pharmaceuticals . These crystal forms are of particular interest because they often show an enhancement of certain properties compared with those of their bulk counterparts.…”

Section: Introductionmentioning

confidence: 99%

“…[1,2] Such polymorphs, termeda st hinfilm, surface-mediated, or substrate-induced phases (SIPs), [3] have mostly been observed for organic semiconductors, but could also be of importance for other classes of molecules, such as pharmaceuticals. [4,5] These crystal forms are of particular interest because they often showa nenhancement of certain properties compared with those of their bulk counterparts. For example, the well-known thin-film phase of the organic semiconductor pentacene has better charge-carrier mobility properties than those of the two known bulk polymorphs.…”

Section: Introductionmentioning

confidence: 99%

Substrate‐Induced Phase of a Benzothiophene Derivative Detected by Mid‐Infrared and Lattice Phonon Raman Spectroscopy

et al. 2018

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The presence of a substrate-induced polymorph of 2,7-dioctyloxy[1]benzothieno[3,2-b]benzothiophene is probed in microscopic crystals and in thin films. Two experimental techniques are used: lattice phonon Raman and IR spectroscopy. The bulk crystal and substrate-induced phase have an entirely different molecular packing, and therefore, their Raman spectra are characteristic fingerprints of the respective polymorphs. These spectra can be unambiguously assigned to the individual polymorphs. Drop-cast and spin-coated thin films on solid substrates are investigated in the as-prepared state and after solvent-vapor annealing. Because Raman spectroscopy is less sensitive with decreasing film thickness, IR spectroscopy is shown to be a more feasible tool for phase detection. The surface-induced phase is mainly present in the as-prepared thin films, whereas the bulk phase is present after solvent-vapor annealing. This result suggests that the surface-induced phase is a metastable polymorph.

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Substrate‐Induced and Thin‐Film Phases: Polymorphism of Organic Materials on Surfaces

Jones

Chattopadhyay

Geerts

et al. 2016

Adv Funct Materials

231

280

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2233wileyonlinelibrary.com to that of the bulk liquid; [ 7 ] order typically exists over a few molecular layers before rapidly decaying to bulk behavior as the distance from the wall increases. [ 8 ] Similar ordering effects can also be observed in the quasiliquids which form on the surface of many solids due to surface melting (also known as premelting): [ 9,10 ] the existence of a liquid-like layer a few molecules thick on the surface of a solid below the melting point of the bulk material. [ 11 ] The structure within this layer is also found to be different to that of the bulk isotropic liquid, [ 12 ] highlighting the ordering occurring at the interface. A converse effect, surface freezing, is also observed in some liquids (primarily n -alkanes with 16 ≤ n ≤ 50), where a solid monolayer may exist at an interface up to ≈30 °C above the bulk melting point while the rest of the compound is molten. [13][14][15] Such phase behavior is strongly dependent on molecular shape and has only been observed for chain molecules, which then form layers similar to self-assembled monolayers (SAMs) at the interface with the liquid bulk. [ 16 ] Further examples of molecular ordering at interfaces can be seen in materials which display liquid crystal (LC) phases, a phase behavior also dependent on molecular shape and generally observed for molecules with a highly anisotropic shape (e.g., rod-like, disc-like or bowl-like molecules). [ 17 ] LCs have properties of both solids and liquids and display long range order which may be orientational and/or positional; various types of LC phases (mesophases) are possible and normally exist only over a certain temperature range (i.e., they are thermotropic); a further property of LCs is that they generally reach thermodynamic equilibrium in the bulk and at interfaces as a result of their short relaxation time. Nematic (N) phases of calamitic LCs (rod-like molecules with cylindrical symmetry) have no positional order but an orientational order which can be described by a unit vector, n , known as the director, which represents the preferred molecular orientation ( Figure 1 , left). A scalar order parameter can also be defi ned which is related to the average angle the long molecular axes make to the director, n .Increased order is seen in smetic phases (Sm) which have both orientational and positional order; for example in a smetic A phase (SmA) molecules form layers (positional ordering of the molecular mass centers) which are oriented normal to the plane of the layers (orientational order), while smetic C phases (SmC) form layers where molecules are oriented with the long molecular axes tilted at an angle to the molecular layer normal However, the factors that drive such a process are not clearly understood or studied in depth. In this feature article, we review the current state of understanding concerning SIPs, giving examples of systems where SIPs have been observed, discussing their origins, and which questions remain to be answered. The role of the substrate in controlling the growth a...

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

Cited by 43 publications

References 30 publications

Emerging role of primary heterogeneous nucleation in pharmaceutical crystallization

Emerging role of primary heterogeneous nucleation in pharmaceutical crystallization

Substrate‐Induced Phase of a Benzothiophene Derivative Detected by Mid‐Infrared and Lattice Phonon Raman Spectroscopy

Substrate‐Induced and Thin‐Film Phases: Polymorphism of Organic Materials on Surfaces

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