Surface-Induced Polymorphism as a Tool for Enhanced Dissolution: The Example of Phenytoin

Reischl, Daniela; Röthel, Christian; Christian, Paul; Roblegg, Eva; Ehmann, Heike; Salzmann, Ingo; Werzer, Oliver

doi:10.1021/acs.cgd.5b01002

Cited by 29 publications

(47 citation statements)

References 36 publications

(80 reference statements)

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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%

“…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 . More recently, a new polymorph of the drug molecule phenytoin was found in thin films that showed improved dissolution properties relative to those of the bulk polymorphs …”

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%

“…[6,7] More recently,anew polymorph of the drug molecule phenytoin was found in thin films that showedi mproved dissolution properties relative to those of the bulk polymorphs. [5] Because SIPs are typically found only in thin films, their study and characterization is not straightforward.F irst, these polymorphs can be difficult to observe. To characterize thin films, specular XRD is ac ommonly used technique that can be easily performed with laboratory-based instrumentation.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2018

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“…[4,5] On the other hand, a surfaceinduced polymorph with enhanced dissolution and orthorhombic system (cell dimensions a = 6.10, b = 12.20, c = 13.95 Å) was obtained. [6] Phenytoin also forms binary crystal compounds with copper complexes, [7] polyethylene glycol, [8] pyridone and pyridyl. [9,10] Being highly lipophilic it can be solubilized in alkali and many organic solvents, but, as the free acid, it is poorly soluble in water.…”

Section: Introductionmentioning

confidence: 99%

Molecular Structure of Phenytoin: NMR, UV-Vis and Quantum Chemical Calculations

Luchian¹,

Vinţeler²,

Chiş³

et al. 2015

Croat. Chem. Acta

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Due to the presence of the carbonyl and imide groups in the structure of 5,5-diphenylhydantoin (DPH), the possibility for this compound to be involved in hydrogen bonding intermolecular interactions is obvious. Even though such interactions are presumably responsible for the mechanism of action of this drug, however, to the best of our knowledge, the self-hydrogen bonding interactions between the DPH monomers have not been addressed till now. Furthermore, studies reporting on the spectroscopic characteristics of this molecule are scarcely reported in the literature.Here we report on the possible dimers of DPH, investigated by quantum chemical calculations at B3LYP/6-31+G(2d,2p) level of theory. Twelve unique DPH dimers were structurally optimized in gas-phase, as well as in ethanol and DMSO and then were used to compute the population-averaged UV-Vis and NMR spectra using Boltzmann statistics. UV-Vis and NMR techniques were employed to assess experimentally the spectroscopical response of this compound. DFT calculations are also used to investigate the structural transformations between the solid and liquid phase, as well as for describing the electronic transitions and for the assignment of NMR spectra of DPH.

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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

228

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-Induced Polymorphism as a Tool for Enhanced Dissolution: The Example of Phenytoin

Cited by 29 publications

References 36 publications

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

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

Molecular Structure of Phenytoin: NMR, UV-Vis and Quantum Chemical Calculations

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

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