TY - JOUR
T1 - Thermodynamics of the Enantiotropic Pharmaceutical Compound Benzocaine and Solubility in Pure Organic Solvents
AU - Cheuk, Dominic
AU - Svärd, Michael
AU - Rasmuson, Åke C.
N1 - Publisher Copyright:
© 2020 The Authors
PY - 2020/11
Y1 - 2020/11
N2 - 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.
AB - 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.
KW - Activity coefficient
KW - Crystallization
KW - Heat capacity
KW - Ideality
KW - Polymorphism
KW - Solubility
KW - Thermodynamics
UR - http://www.scopus.com/inward/record.url?scp=85089752710&partnerID=8YFLogxK
U2 - 10.1016/j.xphs.2020.07.022
DO - 10.1016/j.xphs.2020.07.022
M3 - Article
C2 - 32777220
AN - SCOPUS:85089752710
SN - 0022-3549
VL - 109
SP - 3370
EP - 3377
JO - Journal of Pharmaceutical Sciences
JF - Journal of Pharmaceutical Sciences
IS - 11
ER -