Apparent thermodynamic analysis and the dissolution behavior of levamisole hydrochloride in three binary solvent mixtures

doi:10.1016/j.tca.2019.178375

Thermochimica Acta

Volume 681, November 2019, 178375

https://doi.org/10.1016/j.tca.2019.178375 Get rights and content

Highlights

•
The solubility of levamisole hydrochloride in three binary solvents was determined.
•
Five thermodynamic models were used to correlate the experimental solubility data.
•
The apparent thermodynamic properties of levamisole hydrochloride were discussed.

Abstract

The solubility of levamisole hydrochloride (LH) in binary {methanol (MT) + ethanol (EA), methanol (MT) + 2-propanol (IPA)} solvent mixtures from 283.15 K to 323.15 K and dimethyl sulfoxide (DMSO) + ethanol (EA) from 293.15 K to 333.15 K were obtained under the pressure of 0.1MPa by using a dynamic method. Moreover, the experimental solubility results of LH in this work were correlated well with five thermodynamic models namely “Yaws model, van’t Hoff model, Universal Quasi-Chemical (UNIQUAC) model, non-random two liquid (NRTL) model and general single (GSM) model”. The minimum RMSD and ARD are 0.0064 and 0.17 respectively and they are both calculated with the GSM model. Besides, the apparent thermodynamic properties of LH in the selected binary solvent mixtures were discussed. Analysis results showed that enthalpy-favored mechanism plays a major role in the dissolution process of LH.

Graphical abstract

Introduction

Levamisole hydrochloride (molecular formula: C₁₁H₁₂N₂S·HCl; CAS registry number: 16595-80-5; molar mass: 240.75 g·mol⁻¹; the chemical structure is shown in Fig.1) is an important active pharmaceutical ingredient (API). Levamisole hydrochloride has been widely used as the anti-ascarid and anti-hookworm drugs, it also can be used as a feed additive to improve the efficiency of poultry farming. Crystal form, residual solvents, purify and grain size distribution (GSD) have a vital impact on the storage and transportation (prevent the occurrence of agglomeration) and the efficacy of drugs.

Some pharmaceutical enterprises of levamisole hydrochloride also have to solve such problems. Solubility of drug is an important fundamental data and plays a major role in developing the method of its crystallization and purification, especially for researchers engaged in pharmaceutical enterprises and scientific research institutes. Although the solubility of drugs in various of solvents can be predicted by theoretical and thermodynamic models, the experimental solubility are still important and needed in most cases. In this work, the experimental mole fraction solubility of levamisole hydrochloride in binary mixtures (methanol + ethanol and methanol + 2-propanol) from 283.15 K to 323.15 K, (dimethyl sulfoxide + ethanol) from 293.15 K to 333.15 K were obtained by using a dynamic method. The experimental results were correlated by the Yaws model, van’t Hoff model, UNIQUAC model, NRTL model and GSM model. Furthermore, the apparent dissolution thermodynamic properties, including enthalpy, entropy and Gibbs energy change were calculated.

Section snippets

Materials

Levamisole hydrochloride, IUPAC name: (6S)-6-phenyl-2H,3H,5H,6H-imidazo [2,1-b][1,3] thiazole hydrochloride, was purchased from “Aladdin biochemical co., LTD (Shanghai, China)”. The solvents: MT (IUPAC name: Methanol; CAS registry number: 67-56-1) and EA (IUPAC name: Ethanol; CAS registry number: 64-17-5); IPA (IUPAC name: 2-Propanol; CAS registry number: 67-63-0) and DMSO (IUPAC name: Dimethyl sulfoxide; CAS registry number: 67-68-5) were also obtained from “Aladdin biochemical co., LTD

Yaws model

The Yaws model is usually used to correlate the experimental solubility and the corresponding temperature, which is a semi-empirical model, the Yaws model equation is described as [4,5]: $\ln x^{Yaws} = A + \frac{B}{T / K} + \frac{C}{{(T / K)}^{2}}$ where A, B and C are the “Yaws model” model parameters which can be obtained from correlating a nonlinear relationship analysis of the x₁ values of LH and the absolute temperature T.

van’t Hoff model

The temperature dependence of the mole fraction solubility of levamisole hydrochloride in the three selected

Characterization of LH

The DSC curve of raw levamisole hydrochloride and the excess solid (excess raw levamisole hydrochloride was put into the saturated solutions) collected from the selected solutions, and the DSC curves are shown in Fig. 2. It is obviously to find that there is only one endothermic peak and the onset temperature (generally considered as the fusion point T_m) is 227.0 ℃ (the absolute melting temperature is 500.15 K) according to the DSC curve for the raw LH, and the fusion enthalpy (Δ_fusH) of raw

Conclusion

The solubility of levamisole hydrochloride in binary (MT + EA, MT + IPA) solvents from 283.15 K to 323.15 K and (DMSO + EA) solvents from 293.15 K to 333.15 K were determined under the pressure of 0.1 MPa by using a dynamic method in present work. It is observed that the x₁ of LH reached its maximum value when the mass fraction of EA (δ₂) was 0.400 (temperature from 293.15 K to 298.15 K) in binary (DMSO + EA) solvents; the x₁ of LH reached its maximum value when δ₂ was 0.600 (temperature from

Acknowledgment

This project was financially supported by National Natural Science Foundation of China (Grant No. 21506197, Grant No.21646011).

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Apparent thermodynamic analysis and the dissolution behavior of levamisole hydrochloride in three binary solvent mixtures

Highlights

Abstract

Graphical abstract

Introduction

Section snippets

Materials

Yaws model

van’t Hoff model

Characterization of LH

Conclusion

Acknowledgment

Fluid Phase Equilib.

Fluid Phase Equilib.

Fluid Phase Equilib.

Int. J. Pharm.

J. Mol. Liq.

Int. J. Pharm.

Thermochim. Acta

Thermochim. Acta

Fluid Phase Equilib.

Fluid Phase Equilib.

Fluid Phase Equilib.

J. Mol. Liq.

Eur. J. Pharm. Biopharm.