Thermodynamics of the Enantiotropic Pharmaceutical Compound Benzocaine and Solubility in Pure Organic Solvents

Dominic Cheuk, Michael Svärd, Åke C. Rasmuson

Research output: Contribution to journalArticlepeer-review

Abstract

The thermodynamic relationship between FI and FII of ethyl 4-aminobenzoate (benzocaine) has been investigated. Slurry conversion experiments show that the transition temperature below which FI is stable is located between 302 K–303 K (29 °C–30 °C). The polymorphs FI and FII have been characterised by infrared spectroscopy (IR), Raman spectroscopy, transmission powder X-ray diffraction (XRPD) and differential scanning calorimetry (DSC). The isobaric solid state heat capacities have been measured by DSC. The quantitative thermodynamic stability relationship has been determined in a comprehensive thermodynamic analysis of the calorimetric data. The solubility of both polymorphs has been determined in eight pure organic solvents over the temperature range 278 K–323 K by a gravimetric method. The mole fraction solubility of benzocaine decreases in the order: 1,4-dioxane, acetone, ethyl acetate, chloroform, acetonitrile, methanol, n-butanol and toluene. Comparison with the determined activity of solid benzocaine forms shows that negative deviation from Raoult's law ideality is found in dioxane, acetone and ethyl acetate solutions, and positive deviation in solutions of the other investigated solvents.

Original languageEnglish
Pages (from-to)3370-3377
Number of pages8
JournalJournal of Pharmaceutical Sciences
Volume109
Issue number11
DOIs
Publication statusPublished - Nov 2020

Keywords

  • Activity coefficient
  • Crystallization
  • Heat capacity
  • Ideality
  • Polymorphism
  • Solubility
  • Thermodynamics

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