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

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 Ke303 K (29 Ce30 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 Ke323 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.

Assessment of Binary Agarose–Carbopol Buccal Gels for Mucoadhesive Drug Delivery: Ex Vivo and In Vivo Characterization

“…The melting point of pure BZN was identified by a sharp endothermic peak at approximately 92.1 °C ( Figure 5 ), which corresponds to the value reported in the literature [ 47 ]. For TIB, melting of the pure drug was confirmed as an endothermic peak depression at 161.3 °C [ 42 ].…”

Cyclic Ether–Water Hybrid Electrolyte-Guided Dendrite-Free Lamellar Zinc Deposition by Tuning the Solvation Structure for High-Performance Aqueous Zinc-Ion Batteries

“…The C−O−C stretching vibration (∼834, ∼1109 cm −1 ) (Figure 1d) and the O−H stretching vibration (∼3230, ∼3420 cm −1 ) (Figure 1e) shift to lower frequencies, while the C−H stretching vibration (∼2857, ∼2967 cm −1 ) (Figure 1f) shifts to higher frequencies with the increase in the concentrations of DX, which further validates the interaction between DX and water. 48,49 As shown in Figure S2, the binding energy between DX and the water molecule is higher than that between water molecules, further proving the inclined formation of H−O hydrogen bonding between DX and H 2 O in the bulk solution. As a result, in the presence of DX, the DX molecules can break the solvation sheath of Zn 2+ and promote the water molecules to dissociate from the Zn− H 2 O aquo complex, leading to the increase in nucleation energy and nucleation overpotential (NOP) and benefiting even Zn deposition during the plating process.…”

Thermodynamics and Intermolecular Interactions of Nicotinamide in Neat and Binary Solutions: Experimental Measurements and COSMO-RS Concentration Dependent Reactions Investigations

“…The modulation period was 1 K, while the modulation amplitude was set to 120 s. In order to evaluate the reliability of the C p measurements, a validation using sodium chloride was performed for the temperature range 300–500 K. The deviations from the reference values [ 60 ] did not exceed 2.4%. The relationship between the heat capacity and temperature for nicotinamide supercooled liquid was determined based on the approach described in works of Rasmuson et al [ 61 , 62 , 63 , 64 , 65 ]. First, the sample was heated above the melting peak to 411 K, to ensure that all substance was melted.…”