Conformational polymorphism of the antidiabetic drug chlorpropamide

Abstract

In this paper, the main features of Raman spectroscopy, one of the first choice methods in the study of polymorphism in pharmaceuticals, are presented taking chlorpropamide as a case of study. The antidiabetic drug chlorpropamide (1-[4-chlorobenzenesulphonyl]-3-propyl urea), which belongs to the sulfonylurea class, is known to exhibit, at least, six polymorphic phases. These forms are characterized not only by variations in their molecular packing but also in their molecular conformation. In this study, the polymorphism of chlorpropamide is discussed on the basis of Raman scattering measurements and quantum mechanical calculations. The main spectroscopic features that fingerprint the crystalline forms are correlated with the corresponding crystalline structures. Using a theoretical approach on the energy dependence of the conformers, simulated molecular torsion angles are plotted versus the formation energy, which provides a satisfactory agreement between the torsion angles at the energy minima and the experimental values observed in the different solid forms of chlorpropamide. Copyright

Unusual seeding effect in the liquid-assisted high-pressure polymorphism of chlorpropamide

“…As a result of the kinetic control of nucleation and nuclei growth [28] , different phases can form, depending on the choice of the starting polymorph [29][30][31] , the hydrostatic medium [32][33][34][35][36][37] , or the compression/decompression protocol [26,[38][39][40][41][42] . An antidiabetic drug, chlorpropamide (4-chloro-N-(propylamino-carbonyl)benzenesulfonamide, C 10 H 13 ClN 2 O 3 S), is particularly prone to polymorphism [43,44] . In addition to the commercially available α-polymorph, which is the thermodynamically stable form under ambient conditions [45] , four other polymorphs (β-, γ-, δ-, ε-) can be preserved indefinitely long under ambient conditions.…”

Raman and terahertz spectroscopical investigation of cocrystal formation process of piracetam and 3-hydroxybenzoic acid

“…During the last 20 years the use of Raman and THz spectroscopical techniques in the study of solid-state pharmaceutical compounds has been growing rapidity. A detailed analysis of the literature in this filed reveals that the increased interest in vibrational spectroscopy including to monitor and investigate the solid-state polymorphism [19,20], crystallinity [21][22][23], mechanochemical solid-state reactions [24][25][26], and so on. The most frequent application of vibrational techniques in pharmaceuticals is based on the high sensitivity and selectivity in producing fingerprints of the crystalline structure related modifications in a molecular compound [13,18,19].…”

“…A detailed analysis of the literature in this filed reveals that the increased interest in vibrational spectroscopy including to monitor and investigate the solid-state polymorphism [19,20], crystallinity [21][22][23], mechanochemical solid-state reactions [24][25][26], and so on. The most frequent application of vibrational techniques in pharmaceuticals is based on the high sensitivity and selectivity in producing fingerprints of the crystalline structure related modifications in a molecular compound [13,18,19]. Vibrational spectroscopy methods have been demonstrated to be a high potential alternative to analytical tools such as X-ray power diffractometry (XRPD) and differential scanning calorimetry (DSC) in solid-state identification and quantification [14,15,18,19], especially in-line reaction process monitoring involving two or more molecular crystals [14,15] to obtain more useful information in pharmaceutics-related research fields.…”

Solid State in the Pharmaceutical Industry: A Brief Review

“…Assim, observa-se um grande número de publicações nesta área por parte do meio acadêmico. [1][2][3][4][5][6] Muitas publicações têm sido realizadas por grupos brasileiros ou com participação de seus pesquisadores, [7][8][9][10][11][12] sendo a contribuição nacional para o tema razoavelmente relevante. Recentemente, um artigo de revisão foi publicado, 13 com a perspectiva de divulgar um texto que p opo io asseà ate ialà deà estudoà i t odut ioàaosài i ia tesà oàte a .àMes oà sendo um material de excelente qualidade, algumas considerações também interessantes e que podem nortear o trabalho de quem começa a caminhar nas alvoradas da cristalinidade de fármacos não foram abordadas em tal artigo.…”