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Crystal polymorphs of barbital: news about a classic polymorphic system.

Zencirci N, Griesser UJ, Gelbrich T, Apperley DC, Harris RK - Mol. Pharm. (2013)

Bottom Line: The metastable modification III is present in commercial samples and has a high kinetic stability.The solid-state NMR spectra provide information on aspects of crystallography (viz., the asymmetric units and the nature of hydrogen bonding).The known correlation between specific N-H···O═C hydrogen bonding motifs of barbiturates and certain IR characteristics was used to predict the H-bonded pattern of polymorph IV.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pharmacy, University of Innsbruck , Innrain 52, 6020 Innsbruck, Austria.

ABSTRACT
Barbital is a hypnotic agent that has been intensely studied for many decades. The aim of this work was to establish a clear and comprehensible picture of its polymorphic system. Four of the six known solid forms of barbital (denoted I(0), III, IV, and V) were characterized by various analytical techniques, and the thermodynamic relationships between the polymorph phases were established. The obtained data permitted the construction of the first semischematic energy/temperature diagram for the barbital system. The modifications I(0), III, and V are enantiotropically related to one another. Polymorph IV is enantiotropically related to V and monotropically related to the other two forms. The transition points for the pairs I(0)/III, I(0)/V, and III/IV lie below 20 °C, and the transition point for IV/V is above 20 °C. At room temperature, the order of thermodynamic stability is I(0) > III > V > IV. The metastable modification III is present in commercial samples and has a high kinetic stability. The solid-state NMR spectra provide information on aspects of crystallography (viz., the asymmetric units and the nature of hydrogen bonding). The known correlation between specific N-H···O═C hydrogen bonding motifs of barbiturates and certain IR characteristics was used to predict the H-bonded pattern of polymorph IV.

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Polarized light microphotographs of melt filmpreparations illustratingthe transformations of Btl polymorphs IV→III→I0.
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fig3: Polarized light microphotographs of melt filmpreparations illustratingthe transformations of Btl polymorphs IV→III→I0.

Mentions: A supercooledmelt film of Btl crystallizes to either polymorph IV (afterquench cooling) or polymorph I0 (after slowcooling). These two modifications are easily distinguishable fromone another by their different appearance in polarized light (Figure 2) and different transformation behavior on heating.Both crystallize as aggregates with an internal broad beam structure,but only the crystals of form IV contained characteristiccross-cracks. Polymorph I0 does not transformon heating, but with IV as the initial phase, there aretwo solid–solid transformations (Figure 3). The transition IV→III (100–120°C) started first at cracks and resulted in randomly orientedsmall crystals, which produce an irregular multicolor pattern underpolarized light. The transformation III→I0 occurred at 140–150 °C and producedlarger sections of uniform low-order interference colors (brown, gray,and black) in the sample.


Crystal polymorphs of barbital: news about a classic polymorphic system.

Zencirci N, Griesser UJ, Gelbrich T, Apperley DC, Harris RK - Mol. Pharm. (2013)

Polarized light microphotographs of melt filmpreparations illustratingthe transformations of Btl polymorphs IV→III→I0.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4066893&req=5

fig3: Polarized light microphotographs of melt filmpreparations illustratingthe transformations of Btl polymorphs IV→III→I0.
Mentions: A supercooledmelt film of Btl crystallizes to either polymorph IV (afterquench cooling) or polymorph I0 (after slowcooling). These two modifications are easily distinguishable fromone another by their different appearance in polarized light (Figure 2) and different transformation behavior on heating.Both crystallize as aggregates with an internal broad beam structure,but only the crystals of form IV contained characteristiccross-cracks. Polymorph I0 does not transformon heating, but with IV as the initial phase, there aretwo solid–solid transformations (Figure 3). The transition IV→III (100–120°C) started first at cracks and resulted in randomly orientedsmall crystals, which produce an irregular multicolor pattern underpolarized light. The transformation III→I0 occurred at 140–150 °C and producedlarger sections of uniform low-order interference colors (brown, gray,and black) in the sample.

Bottom Line: The metastable modification III is present in commercial samples and has a high kinetic stability.The solid-state NMR spectra provide information on aspects of crystallography (viz., the asymmetric units and the nature of hydrogen bonding).The known correlation between specific N-H···O═C hydrogen bonding motifs of barbiturates and certain IR characteristics was used to predict the H-bonded pattern of polymorph IV.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pharmacy, University of Innsbruck , Innrain 52, 6020 Innsbruck, Austria.

ABSTRACT
Barbital is a hypnotic agent that has been intensely studied for many decades. The aim of this work was to establish a clear and comprehensible picture of its polymorphic system. Four of the six known solid forms of barbital (denoted I(0), III, IV, and V) were characterized by various analytical techniques, and the thermodynamic relationships between the polymorph phases were established. The obtained data permitted the construction of the first semischematic energy/temperature diagram for the barbital system. The modifications I(0), III, and V are enantiotropically related to one another. Polymorph IV is enantiotropically related to V and monotropically related to the other two forms. The transition points for the pairs I(0)/III, I(0)/V, and III/IV lie below 20 °C, and the transition point for IV/V is above 20 °C. At room temperature, the order of thermodynamic stability is I(0) > III > V > IV. The metastable modification III is present in commercial samples and has a high kinetic stability. The solid-state NMR spectra provide information on aspects of crystallography (viz., the asymmetric units and the nature of hydrogen bonding). The known correlation between specific N-H···O═C hydrogen bonding motifs of barbiturates and certain IR characteristics was used to predict the H-bonded pattern of polymorph IV.

Show MeSH
Related in: MedlinePlus