Infrared identification of barbiturates with particular reference to the occurrence of polymorphism

Abstract

Infrared spectra of twelve substituted barbituric acids, in a total of 34 polymorphic forms, have been compared. Comparison of a sample spectrum with that of an authentic specimen provides a reliable means of identification, provided that both are in the same crystalline form. To ensure consistent production of a single form a specific treatment is recommended for each substance exhibiting polymorphism.

Structural Features, Phase Relationships and Transformation Behavior of the Polymorphs I−VI of Phenobarbital

“…Forms I, II, III, IV, VI, H1, and H0.5 have been investigated in a number of studies, [9][10][11][12]14,7 by thermal analytical methods, 15,2,3,16,7 powder and single-crystal X-ray diffraction, 4,[17][18][19][20][21] and IR spectroscopy. 18,[22][23][24] Additionally, dissolution, 25,5,26 solubility, [27][28][29][30] and bioavailability 31 studies have been carried out. Finally, a number of formulation studies deal with individual forms of Pbtl.…”

Nonamorphism in Flufenamic Acid and a New Record for a Polymorphic Compound with Solved Structures

“…Although this sentiment resonates with the experience of many researchers in the field, there are compounds and molecular classes more prone to give rise to polymorphism. Moreover, there are legendary compounds purported to give rise to more than 10 or even more than 50 polymorphs at atmospheric pressure. It is therefore sobering that when it comes to the most reliable standard for polymorph characterization, single-crystal X-ray diffraction (XRD), only one molecule in the Cambridge Structural Database (CSD) is recognized as the most polymorphic compound and has, since 2005, been considered the molecule with the most structurally characterized polymorphs: 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile (ROY), a pharmaceutical intermediate, has seven structurally characterized forms (Figure ).…”

Polymorphism in phenobarbital: discovery of a new polymorph and crystal structure of elusive form V

“…The polymorphic propensity of PB has intrigued researchers over the last six decades. [28][29][30][31][32][33][34][35][36][37] In total, eleven polymorphs (I-XI), a hydrate (form XII), a hemihydrate (form XIII) and an amorphous phase (form XIV) are reported in the literature, making it one of the benchmark pharmaceuticals for studying polymorphism and crystal structure prediction. 38,39 However, thus far only three polymorphs were amenable to structure elucidation, hinting at a molecule resistant to forming single crystals suitable for structure determination.…”