Quantification and modeling of nanomechanical properties of chlorpropamide α β and γ conformational polymorphs

Biljana Janković, Tatjana Joksimović, Jernej Stare, Evgeniy Losev, Viktoriya Zemtsova, Stane Srčič, Elena Boldyreva

Результат исследования: Научные публикации в периодических изданияхстатьярецензирование

5 Цитирования (Scopus)


The nanomechanical properties of the α-, β-, and γ- conformational polymorphs of chlorpropamide were determined by the dynamic contact module continuous stiffness measurement at nanoindenter. The mechanical anisotropy of the α-polymorph was confirmed by indenting different faces, and its deformational behavior was assigned as ductile. Based on the nanoindentation results, the β and γ forms are moderately hard with plastic flow at contact points. The results revealed a correlation between Young's modulus and inter-planar interaction energy with regard to crystal orientation. Interpretation of the measurements was assisted by two- and three-dimensional periodic density functional theory (DFT) calculations, yielding inter-planar energies of polymorphs along the cell vectors and exhibiting a very good match with the experimental observations. The results suggest that the inter-planar interaction energy could serve as a first-order indicator for ranking the mechanical propensity of crystalline active ingredients. The study confirms the practical aspect of using the α- form for preparing chlorpropamide tablets with a direct compression procedure due to its substantial level of ductility.

Язык оригиналаанглийский
Страницы (с-по)109-116
Число страниц8
ЖурналEuropean Journal of Pharmaceutical Sciences
СостояниеОпубликовано - 15 дек. 2017


Подробные сведения о темах исследования «Quantification and modeling of nanomechanical properties of chlorpropamide α β and γ conformational polymorphs». Вместе они формируют уникальный семантический отпечаток (fingerprint).