New Lidocaine-Based Pharmaceutical Cocrystals: Preparation, Characterization, and Influence of the Racemic vs. Enantiopure Coformer on the Physico-Chemical Properties

Panpan Ma, Balthazar Toussaint, Enrica Angela Roberti, Noémie Scornet, Axel Santos Silva, Luis Castillo Henríquez, Monique Cadasse, Philippe Négrier, Stéphane Massip, Hanh Dufat, Karim Hammad, Cecilia Baraldi, Maria Cristina Gamberini, Cyrille Richard, Stéphane Veesler, Philippe Espeau, Tu Lee, Yohann Corvis

Research output: Contribution to journalArticlepeer-review

Abstract

This study describes the preparation, characterization, and influence of the enantiopure vs. racemic coformer on the physico-chemical properties of a pharmaceutical cocrystal. For that purpose, two new 1:1 cocrystals, namely lidocaine:dl-menthol and lidocaine:d-menthol, were prepared. The menthol racemate-based cocrystal was evaluated by means of X-ray diffraction, infrared spectroscopy, Raman, thermal analysis, and solubility experiments. The results were exhaustively compared with the first menthol-based pharmaceutical cocrystal, i.e., lidocaine:l-menthol, discovered in our group 12 years ago. Furthermore, the stable lidocaine/dl-menthol phase diagram has been screened, thoroughly evaluated, and compared to the enantiopure phase diagram. Thus, it has been proven that the racemic vs. enantiopure coformer leads to increased solubility and improved dissolution of lidocaine due to the low stable form induced by menthol molecular disorder in the lidocaine:dl-menthol cocrystal. To date, the 1:1 lidocaine:dl-menthol cocrystal is the third menthol-based pharmaceutical cocrystal, after the 1:1 lidocaine:l-menthol and the 1:2 lopinavir:l-menthol cocrystals reported in 2010 and 2022, respectively. Overall, this study shows promising potential for designing new materials with both improved characteristics and functional properties in the fields of pharmaceutical sciences and crystal engineering.

Original languageEnglish
Article number1102
JournalPharmaceutics
Volume15
Issue number4
DOIs
StatePublished - Apr 2023

Keywords

  • cocrystallization
  • crystal engineering
  • dissolution kinetics
  • dl-menthol
  • lidocaine
  • physico-chemical compatibility
  • solid state
  • solubility enhancement
  • thermodynamic stability

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