Exploring Solid State Diversity and Solution Characteristics in a Fluorine-Containing Drug Riluzole

Abstract

Solvent drop grinding experiments on riluzole, an organofluorine drug, with different carboxylic acids (mono and di) and pyridine derivatives, resulted in the formation of 10 different co-crystals, one polymorph of a co-crystal, and a salt. The crystal packing is primarily stabilized via strong N−H•••O, O−H•••N, O−H•••O, and N−H•••N hydrogen bonds, in addition to secondary interactions of the type C− H•••F/O and S•••F intermolecular contacts. The melting point of the new crystalline phases was observed to be present in the range of 90−140 °C which is closely related to the melting point (118 °C) of the original API. It was observed that the cocrystals depicted enhanced the solubility and dissolution rate in comparison to that of the free drug.

Role of halogen-involved intermolecular interactions and existence of isostructurality in the crystal packing of —CF3 and halogen (Cl or Br or I) substituted benzamides

“…The importance of interactions involving halogens in the absence of strong hydrogen bonds has been well established in the crystal engineering community (O'Hagan, 2008;Mondal et al, 2018). The evaluation of weak interactions involving halogens in the presence of strong hydrogen bonds has generated extensive interest in recent literature, particularly in the areas of isostructurality (Dey & Chopra, 2017), polymorphism (Prohens et al, 2012;Cruz Cabeza & Bernstein, 2014), cocrystals (Chattoraj et al, 2014;Mondal, Rao et al, 2017;Eccles et al, 2012), crystal structure prediction (Hulme et al, 2005), host-guest chemistry (Noa et al, 2016), nanoindentation (Mondal, Kiran et al, 2017;Rupasinghe et al, 2015) and supramolecular chemistry (Mondal, Yadav et al, 2017;Nagarajan et al, 2014).…”

Crystal structure analysis of the biologically active drug molecule riluzole and riluzolium chloride

“…The conformations of riluzole and of the riluzolium cation in the crystal packing are preserved except for the conformational changes that occur in the -OCF 3 group. The main difference between the two molecular structures can be seen from the magnitude of the torsion angles Ci-Cj-Ok-Cl, Table 1 (Mondal, Rao et al, 2017;Mondal et al, 2018;Thomas et al, 2019;Yadav et al, 2018). Both the structures in the current study crystallized in a centrosymmetric space group.…”

“…Riluzole (RZ) is the only available drug used for the treatment of amyotrophic lateral sclerosis (ALS) and diseases like Parkinson's disease, Huntington's disease and other mood ISSN 2056-9890 and anxiety disorders (Nakane et al, 2016). Even though riluzole is a most important pharmaceutical drug (Doble, 1996), no crystal structure of pure riluzole has been obtained to date, although several methods have been tried in the past (Mondal, Rao, et al, 2017;Mondal et al, 2018;Thomas et al, 2019;Yadav et al, 2018).…”

Insight into the Formation of Heteromolecular Hydrogen Bonds between Dasatinib and GRAS Molecules

“…Co-crystals, − salts, eutectic mixtures, and co-amorphous solids , of Biopharmaceutics Classification System (BCS) class II and class IV drugs with the Food and Drug Administration (FDA) approval generally recognized as safe (GRAS) substances have received attention as one of the promising methods to enhance the solubility, dissolution rate, and stability of solid active pharmaceutical ingredient (API). − The design approach for multicomponent crystal formation is often based on the concept of crystal engineering. − Noncovalent interactions , (namely, hydrogen-bonding, halogen-bonding, and van der Waals interactions) between an API molecule and a coformer facilitate the crystallization as a co-crystal or salt with a specific stoichiometric ratio. Multicomponent crystals of two components (API and coformer) can be achieved using mechanochemical grinding in a mortar and pestle or a ball mill. − Co-amorphous and eutectic mixtures are the byproducts of such co-crystallization events, which can also enhance the dissolution and bioavailability of an API in the aqueous medium …”