Crystallization of (±)-Modafinil in Gel:  Access to Form I, Form III, and Twins

Abstract

Single crystals of (()-modafinil have been grown in gel medium obtained from the hydrolysis and condensation of tetramethoxysilane (TMOS). Three different crystal morphologies have been highlighted, corresponding to two modifications and a twin. The first polymorphic form was found to match with the known monoclinic form I (P2 1 /a, Z′ ) 2, a ) 14.502 Å, b ) 9.678 Å, c ) 20.844 Å, and β ) 110.17°). The determination of the second form allowed us to validate the previously predicted form III (orthorhombic Pna2 1 , Z′ ) 2, a ) 14.510 Å, b ) 9.710 Å, c ) 19.569 Å). The analysis of the twinned bodies and the structural similarities between form I and form III allowed us to identify the twin law: a stacking fault of (001) form I leading to a form III like interface. The analysis of the structures also suggested possible multitwinning.

Absorbing a Little Water: The Structural, Thermodynamic, and Kinetic Relationship between Pyrogallol and Its Tetarto-Hydrate

“…Since types A and B structures are alternative packing modes of the same stack of O–H···O C 1 1 (6) chains, this might result in the occurrence of type B stacking faults in the AH. Having energetically competitive modes of combining 2D sheets has accounted for polymorphism and/or stacking disorder in aspirin, 89 phloroglucinol dihydrate, 59 or modafinil 90 and may account for the occurrence of concomitant polymorphism 91 (e.g., aprepitant 92 and progesterone 93 ). Since the alternate type A packings (Figure S10 of the Supporting Information) could rearrange easily to the more stable experimental packing, this significantly reduces the possibility that these could be found as long-lived metastable anhydrate polymorphs.…”

Cavity-containing supramolecular gels as a crystallization tool for hydrophobic pharmaceuticals

“…13 One emerging potential application of such reversible and synthetically versatile gels is in the area of pharmaceutical crystallization. [21][22][23][24][25] Control of polymorphic or solvate form is of key industrial importance. [26][27][28][29] Gels based on LMWGs represent a highly tuneable medium adaptable to a range of solvents including those commonly used in pharmaceutical manufacture and they offer the possibility of specific gelator-solute interactions which may influence the solid form outcome and hence make LMWGs a useful part of a pharmaceutical solid form screening strategy.…”

Polymorphism and Solvatomorphism 2006

“…Single crystals of racemic modafinil have been grown in gels, which yielded two polymorphs and a twinned crystal depending on the exact details of the crystallization. 28 The process was able to yield a crystallographic grade Form-III product that had previously only been obtained in a powdered state, thus enabling solution of the crystal structure and a comparison of the structural differences between the two polymorphs.…”