TY - JOUR

T1 - Quantification and modeling of nanomechanical properties of chlorpropamide α β and γ conformational polymorphs

AU - Janković, Biljana

AU - Joksimović, Tatjana

AU - Stare, Jernej

AU - Losev, Evgeniy

AU - Zemtsova, Viktoriya

AU - Srčič, Stane

AU - Boldyreva, Elena

N1 - Publisher Copyright: © 2017 Elsevier B.V.

PY - 2017/12/15

Y1 - 2017/12/15

N2 - 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.

AB - 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.

KW - Chlorpropamide

KW - Density functional theory

KW - Indentation hardness

KW - Inter-planar interaction energy

KW - Nanoindentation

KW - Young's modulus

KW - COMPACTION

KW - FORM

KW - BEHAVIOR

KW - INDENTATION

KW - TOTAL-ENERGY CALCULATIONS

KW - MECHANICAL-PROPERTIES

KW - INITIO MOLECULAR-DYNAMICS

KW - HIGH-PRESSURE POLYMORPHISM

KW - HARDNESS

KW - PHARMACEUTICAL CRYSTALS

KW - Chlorpropamide/chemistry

KW - Models, Chemical

KW - Tablets

KW - Molecular Conformation

KW - Crystallization

KW - Solubility

KW - Anisotropy

KW - Mechanical Phenomena

UR - http://www.scopus.com/inward/record.url?scp=85020922715&partnerID=8YFLogxK

U2 - 10.1016/j.ejps.2017.06.013

DO - 10.1016/j.ejps.2017.06.013

M3 - Article

C2 - 28606802

AN - SCOPUS:85020922715

VL - 110

SP - 109

EP - 116

JO - European Journal of Pharmaceutical Sciences

JF - European Journal of Pharmaceutical Sciences

SN - 0928-0987

ER -