Modulation of the powder properties of lamotrigine by crystal forms

Oisín N. Kavanagh, Chenguang Wang, Gavin M. Walker, Changquan Calvin Sun

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


The mechanical properties of powders determine the ease of manufacture and ultimately the quality of the oral solid dosage forms. Although poor mechanical properties of an active pharmaceutical ingredient (API) can be mitigated by using suitable excipients in a formulation, the effectiveness of that approach is limited for high dose drugs or multidrug tablets. In this context, improving the mechanical properties of the APIs through solid form optimisation is a good strategy to address such a challenge. This work explores the powder and tableting properties of various lamotrigine (LAM) solid forms with the aim to facilitate direct compression by overcoming the poor tabletability of LAM. The two drug-drug crystals of LAM with nicotinamide and valproic acid demonstrate superior flowability and tabletability over LAM. The improved powder properties are rationalised by structure analysis using energy framework, scanning electron microscopy, and Heckel analysis.

Original languageEnglish (US)
Article number120274
JournalInternational journal of pharmaceutics
StatePublished - Feb 15 2021

Bibliographical note

Funding Information:
OK wishes to thank the Irish Fulbright Commission for their support to facilitate this collaboration and Fiona Hogan and Caoimhe Murphy for their help in obtaining preliminary data and for stimulating discussions. This publication was also supported by a research grant from Science Foundation Ireland (12/RC/2275/2). 12/RC/2275/2 is co-funded under the European Regional Development Fund. We acknowledge the Minnesota Supercomputing Institute (MSI) at the University of Minnesota for providing resources that contributed to the research results reported within this paper. URL:

Funding Information:
O.K. was responsible for the conceptualisation, methodology, investigation, visualisation. C.W. and C.C. Sun preformed the energy framework analysis. G.W. acquired financial support to enable the work and supervised the project. All authors discussed the results and contributed to the writing, reviewing and editing of the data within the manuscript.

Publisher Copyright:
© 2021 The Author(s)


  • Cocrystal
  • Crystal engineering
  • Direct compaction
  • High drug load
  • Multidrug
  • Solid form optimisation
  • Tableting


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