Polymorphism of Purpurin and Low-level Detection of the Noncentrosymmetric form by Second Harmonic Generation...

Nonlinear optical imaging based on second harmonic generation (SHG) provides rapid and highly selective detection of polar crystals. Purpurin (PUR) is a natural product with multiple pharmacological activities. Two polymorphs of PUR show distinct crystal packing and structural symmetry, where form I crystallizes in a polar space group and form II crystallizes in a centrosymmetric crystal structure. The two polymorphs are monotropically related, with form I being the thermodynamically stable form, as suggested by slurry experiments, in-situ Raman spectroscopy and crystal structure prediction (CSP). The specificity of SHG to the polar crystals of form I allows rapid polymorphism detection at the limit of individual crystals. SHG is also able to detect low levels of form I in a tablet matrix dominated by amorphous excipients. This study shows that SHG microscopy can achieve the rapid and sensitive detection of noncentrosymmetric crystals in solid dosage forms, which is especially helpful for the early detection of unwanted polymorphic conversion or crystallization of amorphous drugs in formulations and final products.