Plasticity in zwitterionic drugs: the bending properties of Pregabalin and Gabapentin and their hydrates

Abstract

The investigation of mechanical properties in molecular crystals is emerging as a novel area of interest in crystal engineering. Indeed, good mechanical properties are required to manufacture pharmaceutical and technologically relevant substances into usable products. In such endeavour, bendable single crystals help to correlate microscopic structure to macroscopic properties for potential design. The hydrate forms of two anticonvulsant zwitterionic drugs, Pregabalin and Gabapentin, are two examples of crystalline materials that show macroscopic plasticity. The direct comparison of these structures with those of their anhydrous counterparts, which are brittle, suggests that the presence of water is critical for plasticity. In contrast, structural features such as molecular packing and anisotropic distribution of strong and weak interactions seem less important.

Plasticity enhancement in pharmaceutical drugs by water of crystallization: unusual slip planes

“…Recently, a few reports have been published on the role of water molecules in obtaining twistable twodimensional plastic crystals (Saha et al, 2018;Hu et al, 2019). The report by Khandavilli et al (2019) contrasts with this work as the interactions involved in the case of water are strong compared with the weak interactions found in other known plastic crystals. Hence, this work raises some interesting questions related to the dynamics of water molecules and their hydrogen bonds in crystal structures (Panda et al, 2017).…”

“…The water of crystallization in the zwitterionic drugs, pregabalin and gabapentin, facilitates high plasticity in their hydrate forms compared with the anhydrous forms, which are brittle. Reproduced from Khandavilli et al (2019).…”

“…Reporting in IUCrJ, Khandavilli et al (2019) have shown a rare plastic bending behaviour in hydrate forms of two anticonvulsant zwitterionic drugs, pregabalin and gabapentin. Interestingly, the anhydrous forms of both drugs, despite close structural similarity, do not bend plastically.…”

“…The solutions sought currently using empirical methods are tedious and expensive. Hence, further development of a scientific basis in this regard by systematic studies, such as Khandavilli et al (2019), will reduce dependency on the inefficient empirical methods currently used in industry.…”

Plastically Bendable Crystals of Flufenamic Acid Form III

“…[1][2][3][4][5] From the perspective of applications, the plastic and elastic crystals are attractive since they have both mechanical exibility and crystallinity. 6,7 Combined with other functions, these exible organic single crystals have potential applications in various elds, such as pharmaceuticals, [8][9][10][11] optical devices, [12][13][14][15][16][17] arti cial mechanosensors, 18 bioinspired materials 19,20 and molecular machinery 21 . Thus, the investigation of organic crystals with unique mechanical properties is gradually becoming a hot topic in crystal engineering.…”