Improving Tabletability of Excipients by Metal-Organic Framework-Based Cocrystallization: a Study of Mannitol and CaCl2



To improve tabletability of pharmaceutical excipient mannitol by forming cocrystal with metal-organic framework (MOF) structure.


Mannitol was cocrystallized with CaCl2 by slurry method and solvent evaporation method. The obtained cocrystal was characterized by SCXRD, PXRD, and thermal analysis. Comparative study on tabletability between cocrystal and β-mannitol were then conducted. Differences in tabletability were subsequently analyzed using the bonding area-bonding strength (BA-BS) model and correlated with their crystal structures.


The prepared cocrystal contains mannitol, CaCl2 and water in molar ratio of 1:1:2 (i.e. mannitol·CaCl2·2H2O) and all the Ca2+ in the cocrystal are linked together by mannitol molecules through an infinite coordination network, demonstrating a typical MOF structure. Compared with β-mannitol, such MOF-based cocrystal showed improved tabletability (~2-fold increased tensile strength) and reduced lamination tendency (~3-fold increased minimum compaction pressure to occur lamination). The tabletability improvement of cocrystal was dominated by its higher BS, which is attributed to stronger intermolecular interactions. The reduced lamination tendency was attributed to its lower in-die elastic recovery than β-mannitol.


MOF-based cocrystallization will be a promising and valuable approach to tailor mechanical properties of pharmaceutical materials in order to achieve better pharmaceutical performance.

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Bonding area


Bonding strength


Cambridge Crystallographic Data Centre


Cambridge Structural Database


Density function theory


Differential scanning calorimetry


Dynamic vapor sorption


Inorganic Crystal Structure Database


Metal-organic framework


Powder X-ray diffraction


Single crystal X-ray diffraction


Thermal gravimetric analysis


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Correspondence to Jianjun Zhang or Yuan Gao or Shuai Qian.

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Cheng, H., Wei, Y., Wang, S. et al. Improving Tabletability of Excipients by Metal-Organic Framework-Based Cocrystallization: a Study of Mannitol and CaCl2. Pharm Res 37, 130 (2020).

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Key Words

  • bonding strength
  • cocrystal
  • Mannitol
  • MOF
  • tabletability