Structural description of the marketed form of valsartan: A crystalline mesophase characterized by nanocrystals and conformational disorder

Valsartan is an antihypertensive drug, recognized to be marketed in an amorphous state, different from that obtained by quenching the liquid state below Tg. This is an unusual and very original situation, given that the amorphous state is unstable. Low-wavenumber Raman spectroscopy and X-ray diffraction investigations were carried out on the various solid-state forms of valsartan. It was found that the marketed form is not amorphous and can be described in terms of mesophase in which the long-range order of the stable crystal is limited on the lengthscale of tens nanometers, inducing a melting temperature lower than that of the stable crystalline state, inherent to the crystallite size. This unusual physical state of a marketed drug was correlated to the relative population of cis–trans conformers, preventing the development of the hydrogen-bond network distinctive of the long-range order in the crystalline state.