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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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PXRD patternsof Btl forms (experimental, solid lines; simulatedon the basis of single-crystal data from ref (11), dotted lines).
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fig6: PXRD patternsof Btl forms (experimental, solid lines; simulatedon the basis of single-crystal data from ref (11), dotted lines).

Mentions: The forms I0, III, IV, and V arereadily distinguishable from one another by their PXRD patterns (Figure 6), and the experimental patterns of I0, III, and V were consistentwith the relevant literature data.6,7,11 A special preparation method was required for form IV, which transforms readily to III upon mechanicaltreatment. Representative diffractograms of form IV couldbe finally recorded from film preparations prepared on a coverslip,which then was mounted on a silicon holder. Only a rather poor qualitydiffraction pattern affected by preferred orientation was obtainedwith this design. Better diffractograms were obtained with melt preparationsthat were directly produced in a capillary. However, the quality ofthe obtained PXRD data for IV was not sufficient forthe determination of unit cell parameters, but these data matchedvery well with reflections reported by Huang6a (“form III”; no indices; PDF 00-005-0111, ICDD 2005).


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

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

PXRD patternsof Btl forms (experimental, solid lines; simulatedon the basis of single-crystal data from ref (11), dotted lines).
© Copyright Policy
Related In: Results  -  Collection

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

fig6: PXRD patternsof Btl forms (experimental, solid lines; simulatedon the basis of single-crystal data from ref (11), dotted lines).
Mentions: The forms I0, III, IV, and V arereadily distinguishable from one another by their PXRD patterns (Figure 6), and the experimental patterns of I0, III, and V were consistentwith the relevant literature data.6,7,11 A special preparation method was required for form IV, which transforms readily to III upon mechanicaltreatment. Representative diffractograms of form IV couldbe finally recorded from film preparations prepared on a coverslip,which then was mounted on a silicon holder. Only a rather poor qualitydiffraction pattern affected by preferred orientation was obtainedwith this design. Better diffractograms were obtained with melt preparationsthat were directly produced in a capillary. However, the quality ofthe obtained PXRD data for IV was not sufficient forthe determination of unit cell parameters, but these data matchedvery well with reflections reported by Huang6a (“form III”; no indices; PDF 00-005-0111, ICDD 2005).

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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