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Insights into how carbon chain length and branch position of alcohol solvents affect solid–liquid thermodynamic behavior of form I of probucol

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Abstract

To address the problem that how straight-chain and branched solvent affect the solubility of active pharmaceutical ingredient, in this work, the molar fraction solubility of form I of probucol in five alcohols with straight and branched alcohols was determined by gravimetric method ranging from 278.15 to 323.15 K. The results showed that the equilibrium solubility of probucol is temperature-dependent and increased monotonically with temperature. More importantly, our findings show that the solubility of probucol rose as the number of straight-chain carbons grew and that it is more soluble in straight-chain alcohols than in branched alcohols with an equivalent carbon count. Furthermore, we conclude that the solubility of probucol in various solvents in straight-chain alcohols is co-dominated by solvent polarity and cohesive energy density, while in branched alcohols, the solubility of PBL is co-dominated by steric hindrance and temperature. Then, three thermodynamic models were employed to correlate the experimental solubility data and derive the dissolution thermodynamic properties of PBL. Our results indicated that except for ethanol, the dissolution process of PBL in other alcohols is enthalpy-driven and spontaneous, while in the case of ethanol, the dissolution of PBL transforms from entropy-driven to enthalpy-driven.

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Abbreviations

a 1, a 2 :

The activities of the solute and solvent, respectively

A, B, C :

The parameters of the Apelblat model

H E :

The excess enthalpy (kJ mol−1)

m 1 :

The mass of form I of PBL (g)

m 2 :

The mass of solvent (g)

M 1 :

The molecular mass of form I of PBL (g mol−1)

M 2 :

The molecular mass of solvent (g mol−1)

R :

The gas constant (J K−1 mol−1)

T :

The absolute temperature (K)

T m :

The absolute melting temperature of form I of PBL (K)

T mean :

The average absolute temperature (K)

u r :

The relative standard uncertainty

U :

The standard uncertainty

x i :

The mole fraction solubility of form I of PBL (mol mol−1)

x i exp :

The experimental solubility of form I of PBL (mol mol−1)

x i exp :

The calculated solubility by thermodynamic models (mol mol−1)

ζ H :

The relative contribution of enthalpy

ζ TS :

The relative contribution of entropy

∆fus H :

The fusion enthalpy of form I of PBL (kJ mol−1)

∆fus S :

The fusion entropy of form I of PBL (kJ mol−1)

∆diss G° :

The dissolution Gibbs free energy of real solution (kJ mol−1)

∆diss H° :

The dissolution enthalpy of solution (kJ mol−1)

∆diss S° :

The dissolution entropy of solution (J mol−1 K−1)

λ, h :

The parameters of the λh equation

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Acknowledgements

The authors are grateful to the financial support of the National Natural Science Foundation of China (Grant Nos. NNSFC 22178272 and NNSFC 22108204); National Key Research and Development Program of China (No. 2022YFC2904000); Training Program for Changjiang Scholars and Innovative Research Team in University ([2013] 373); Innovative Research Team of Tianjin Municipal Education Commission (TD13-5008) and Yangtze Scholars and Innovative Research Team in Chinese University (IRT-17R81).

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  1. Tianjin Key Laboratory of Brine Chemical Engineering and Ecological Utilization of Resources, Tianjin Engineering Center of Marine Chemical Engineering & Technology, Tianjin Key Laboratory of Multiplexed Identification for Port Hazardous Chemicals, College of Chemical Engineering and Materials Science, Tianjin University of Science and Technology, Tianjin, 300457, China

    Rong Zhang, Wei Wang, Jiaqi Li, Shijie Xu & Yanfei Wang

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Zhang, R., Wang, W., Li, J. et al. Insights into how carbon chain length and branch position of alcohol solvents affect solid–liquid thermodynamic behavior of form I of probucol. J Therm Anal Calorim 149, 2941–2952 (2024). https://doi.org/10.1007/s10973-024-12883-5

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