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



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.


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.


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.


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.

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Bonding area


Bonding strength




Differential scanning calorimetry




Microcrystalline cellulose




Powder X-ray diffractometry


Relative humidity


Thermogravimetric analysis

P y :

Mean yield pressure


Tablet porosity


Tablet density

ρt :

Powder true density

σ0 :

Tensile strength of the tablet at zero porosity


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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 (

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Correspondence to Changquan Calvin Sun.

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Shi, Z., Wang, C. & Sun, C.C. Molecular Origin of the Distinct Tabletability of Loratadine and Desloratadine: Role of the Bonding Area – Bonding Strength Interplay. Pharm Res 37, 133 (2020).

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Key Words

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