Valsartan
(VAL) is an antihypertensive drug marketed in an amorphous
form. Amorphous materials can have different physicochemical properties
depending on preparation method, thermal history, etc., but the nature
of such materials is difficult to study by diffraction techniques.
This study characterizes two different amorphous forms of valsartan
(AR and AM) using solid-state NMR (SSNMR) as a primary investigation
tool, supported by solution-state NMR, FT-IR, TMDSC, and dissolution
tests. The two forms are found to be clearly distinct, with a significantly
higher level of structural arrangement in the AR form, as observed
in 13C, 15N, and 1H SSNMR. 13C and 15N NMR indicates that the fully amorphous material
(AM) contains an approximately equal ratio of cis–trans conformers about the amide bond, whereas
the AR form exists mainly as one conformer, with minor conformational
“defects”. 1H ultrafast MAS NMR shows significant
differences in the hydrogen bonding involving the tetrazole and acid
hydrogens between the two materials, while 15N NMR shows
that both forms exist as a 1,2,3,4-tetrazole tautomer. NMR relaxation
times show subtle differences in local and bulk molecular mobility,
which can be connected with the glass transition, the stability of
the glassy material, and its response to aging. Counterintuitively
the fully amorphous material is found to have a significantly lower
dissolution rate than the apparently more ordered AR material.