Feasibility of thermal methods on screening, characterization and physicochemical evaluation of pharmaceutical cocrystals

Hongji Liu, Henry H.Y. Tong, Zhengzheng Zhou

Research output: Contribution to journalReview articlepeer-review

6 Citations (Scopus)


Pharmaceutical cocrystals, an important multi-component complex compressing at least two molecules linked by noncovalent bonds within the same crystal lattice, have shown a great promise in development of new drugs by improving their physicochemical properties of active pharmaceutical ingredients, such as solubility, dissolution rate, stability, permeability, tabletability and bioavailability. Consequently, they have substantially benefited the pharmaceutical industry, since many APIs in preclinical stage exhibit poor solubility or permeability, with 90% of all new drugs classified as Biopharmaceutics Classification System II/IV classes. At present, various instrumental-based methods, such as X-ray diffraction, thermal methods, nuclear magnetic resonance, Fourier transform infrared spectroscopy and Raman spectroscopy, have been developed to identify and characterize pharmaceutical cocrystals. Among them, the thermal method is a fast, economical and solvent-free technique for cocrystals’ study. In the present work, the authors review various thermal analyses used in the characterization of pharmaceutical cocrystals including differential thermal analysis, differential scanning calorimetry, temperature-modulated differential scanning calorimetry, thermogravimetric analysis, dynamic vapor sorption, hot-stage microscopy, thermal micro-Raman spectroscopy, hot-melt extrusion and thermal hyphenated technologies. The advantages of thermal analysis used in solid-state pharmaceuticals were highlighted. The future trend of thermal analysis application in pharmaceutical cocrystals was summarized. Graphical abstract: [Figure not available: see fulltext.]

Original languageEnglish
Pages (from-to)12947-12963
Number of pages17
JournalJournal of Thermal Analysis and Calorimetry
Issue number23
Publication statusPublished - Dec 2022


  • Cocrystal
  • Crystal engineering
  • Solid-sate forms
  • Solubility
  • Thermal analysis


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