Inversion of the Relative Stability between Two Polymorphic Forms of (±) Modafinil under Dry High-Energy Milling: Comparisons with Results Obtained under Wet High-Energy Milling

Among the seven different forms of (±) modafinil, form I is the most stable variety (at whatever the temperature, T ), and form III is very close to form I in terms of lattice energy. Under high-energy milling (HEM), every modification converts into a defective form III. The inversion of “stability” between form I and form III is then evidenced when a high-powered mechanical flux of energy is applied. When 3% mass/mass of water a very poor solvent for this racemic compound is introduced in the vials, the same types of experiments lead to defective form I. This study tends to show that whatever the number of polymorphic forms in the temperature, pressure ( T, P ) space, a single variety exists as a steady state for a given set of HEM parameters.