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

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)109-116
Number of pages8
JournalEuropean Journal of Pharmaceutical Sciences
Volume110
DOIs
Publication statusPublished - 15 Dec 2017

Keywords

  • Chlorpropamide
  • Density functional theory
  • Indentation hardness
  • Inter-planar interaction energy
  • Nanoindentation
  • Young's modulus
  • COMPACTION
  • FORM
  • BEHAVIOR
  • INDENTATION
  • TOTAL-ENERGY CALCULATIONS
  • MECHANICAL-PROPERTIES
  • INITIO MOLECULAR-DYNAMICS
  • HIGH-PRESSURE POLYMORPHISM
  • HARDNESS
  • PHARMACEUTICAL CRYSTALS
  • Chlorpropamide/chemistry
  • Models, Chemical
  • Tablets
  • Molecular Conformation
  • Crystallization
  • Solubility
  • Anisotropy
  • Mechanical Phenomena

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