Structural and energetic aspects of a new bupropion hydrochloride polymorph

Crystalline bupropion hydrochloride [(±)1-(3-chlorophenyl)-2-[(1,1-dimethylethyl)amino]-1-propanone hydrochloride], recently characterized as form 1, was found to undergo, upon storage at RT within months, a solid–solid conversion to a new polymorphic form, hereafter named form 2, containing a markedly different molecular conformer in the solid state. This new form, available only as a polycrystalline material, has been fully characterized using structural X-ray powder diffraction methods, coupled to thermoanalytical analyses. The relative stability of the two crystalline phases (forms 1 and 2) was compared by quantum mechanics calculations including density functional methods specific for solid state molecular systems. Bupropion hydrochloride form 2 crystallizes in the orthorhombic space group Pbca with Z = 8, a = 27.2853(5) Å, b = 8.7184(3) Å, c = 12.0422(3) Å, V = 2864.7(1) Å3, as centrosymmetric dimers, thanks to the presence of N–H…Cl interactions, and μ2-bridging chloride ions, each connected to two protonated amine moieties.

► A new polymorphic form of bupropion hydrochloride has been found. ► The new polymorph (named form 2) was fully characterized by X-ray powder diffraction. ► Interconversion between the two crystalline phases was assessed by thermal analyses. ► Quantum mechanics calculations were carried out in the gas and in the solid state.