Access to Several Polymorphic Forms of (±)-Modafinil by Using Various Solvation–Desolvation Processes

Abstract

The solid state landscape of (±)-modafinil presents several polymorphic forms and solvates. Some of these polymorphic forms ((±)-Forms V and VI) can only be obtained by means of desolvation of solvates ((±)-modafinil chloroform solvate and acetonitrile solvate). Moreover, a new hydrate ((±)-modafinil monohydrate) is obtained from an original protocol which uses a physical mixture of both enantiomers rather than the racemic compound. All these solvates present an efflorescent behavior, and this study highlights the formation of various polymorphic forms from the same solvate according to the temperature of desolvation. Indeed, when the desolvation process is performed below or above the glass transition temperature (T g) of the anhydrous modafinil, the resulting nonsolvated phases differ.

Time-Resolved Cooperative Motions in the Solid-State Dehydration of Thymine Hydrate

“…Subsequent cooling to room temperature and exposure to RH ∼ 70% yielded a final powder pattern that was majority Td 2 with some minor TH impurity. We cannot discount the possibility of a simultaneous transformation from Td 1 to Td 2 under high RH conditions, as the Td 1 structure has been shown to be metastable relative to other anhydrous forms in humid environments . The sPXRD data indexed to a C2 cell and was subjected to Pawley refinement, with simulated annealing used for structure solution.…”

“…We cannot discount the possibility of a simultaneous transformation from Td 1 to Td 2 under high RH conditions, as the Td 1 structure has been shown to be metastable relative to other anhydrous forms in humid environments. 8 The sPXRD data indexed to a C2 cell and was subjected to Pawley refinement, with simulated annealing used for structure solution. The final refinement yielded a structure with unit cell parameters a = 6.7729(7) Å, b = 6.8409(8) Å, c = 12.843(2) Å, ß = 104.958(11)°, and Vol = 574.90(13) Å 3 and an R wp = 13.38% and GOF = 5.46.…”

“…Since hydrated and anhydrous forms exhibit different physical properties (e.g., solubility and bioavailability), it is important ensure that the external conditions under which they are maintained do not allow for transformations between these different solid-state forms. On the other hand, the intentional dehydration of hydrates can be used as a means to create novel anhydrous crystalline forms that may not be accessible directly from solution crystallization. − Regardless of whether the goal is to prevent or encourage solid state dehydration reactions, our ability to predict them is limited by an incomplete understanding of the molecular-level mechanisms by which these processes occur.…”

Polymorphism and Particle Formation Pathway of Carbamazepine during Sonoprecipitation from Ionic Liquid Solutions

“…Desolvation of the solvates or hydrates remains an area of research that is actively pursued with the aim of obtaining the anhydrous polymorphs under some controlled conditions. − If properly controlled, the desolvation method can be successfully used to obtain the desired polymorphs of a compound from its respective solvates or hydrates. In this work also, we observed that the desolvation of the DH form of CBZ under a vacuum resulted in the formation of the anhydrous CBZ polymorphs.…”

Observation of Rapid Desolvation of Hexafluorobenzene Involving Single-Crystal-to-Single-Crystal Phase Transition in a Nonporous Organic Host

“…In such a scenario, the solvent molecules can incorporate into the lattice through potential host–guest interactions which provides additional stability to the framework structure . The loss of the guest molecule from such a molecular host in the absence of intrinsic porosity does not allow quick solid state rearrangement to maintain the three-dimensional (3D) periodicity and leads to disruption of single crystallinity,which makes the event of desolvation involving single-crystal-to-single-crystal (SCSC) phase transition extremely rare. ,− Moreover, the structural transformation with the removal of guest molecules from crystal lattice often needs potential stimuli such as elevated temperature, light, or mechanical forces which often destroy the crystalline nature of the material with reduced properties. In this regard, spontaneous solvent elimination at room temperature (RT, 20–25 °C) from a nonporous organic host lattice with quick reorganization to another polymorphic form in SCSC fashion demands significant attention in both fundamental and application based research.…”