Molecular Origin of the Distinct Tabletability of Loratadine and Desloratadine: Role of the Bonding Area – Bonding Strength Interplay

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: To explain the different tabletability of two structurally similar H1-receptor antihistamine drugs, loratadine (LOR) and desloratadine (DES), based on the molecular basis of bonding area and bonding strength. Methods: LOR and DES were characterized by powder X-ray diffractometry, thermal analysis, and dynamic water sorption. The compressibility, tabletability, compactibility, and Heckel analysis of their bulk powders and formulations were evaluated. A combined energy framework and topological analysis was used to characterize the crystal structure – mechanical property relationship. Surface energy of bulk powder was assessed by contact angle measurement using the Owens/Wendt theory. Results: Both LOR and DES bulk powders are phase pure and stable under compaction. The superior tabletability of LOR is attributed to both larger bonding area (BA) and higher interparticle bonding strength (BS). The larger BA of LOR results from its experimentally established higher plasticity, which is explained by the presence of more densely packed molecular layers with smooth surface topology. The higher BS of LOR corresponded to its significantly higher dispersive component of the surface energy. Conclusions: This work provides new insights into the molecular origins of BA and BS, which can be applied to improve mechanical properties and tableting performance of drugs through appropriate crystal engineering.

Original languageEnglish (US)
Article number133
JournalPharmaceutical research
Volume37
Issue number7
DOIs
StatePublished - Jul 1 2020

Bibliographical note

Funding Information:
We thank the Minnesota Supercomputing Institute (MSI) at the University of Minnesota for providing the resources that contributed to the research results reported within this paper (http://www.msi.umn.edu).

Publisher Copyright:
© 2020, Springer Science+Business Media, LLC, part of Springer Nature.

Keywords

  • bonding area
  • bonding strength
  • desloratadine
  • loratadine
  • plasticity
  • surface energy
  • tabletability

PubMed: MeSH publication types

  • Comparative Study
  • Journal Article

Fingerprint

Dive into the research topics of 'Molecular Origin of the Distinct Tabletability of Loratadine and Desloratadine: Role of the Bonding Area – Bonding Strength Interplay'. Together they form a unique fingerprint.

Cite this