Measurement and modeling of solubility of gliclazide (hypoglycemic drug) and captopril (antihypertension drug) in supercritical carbon dioxide

doi:10.1016/j.supflu.2021.105244

The Journal of Supercritical Fluids

Volume 174, August 2021, 105244

https://doi.org/10.1016/j.supflu.2021.105244 Get rights and content

Highlights

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Solubility of gliclazide and captopril in ScCO₂ was measured.
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Experiments were conducted at 308.2–328.2 K in a pressure range of 10–18.6 MPa.
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Experimental data self-consistency was confirmed by semi-empirical models.
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Two approaches based on Peng-Robinson EOS provide good correlation results.
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PR+MHV1+COSMOSAC predictions are within a factor of three of experiment.

Abstract

The solubility of drugs in supercritical carbon dioxide (ScCO₂) is crucial information for crystal engineering designs and pharmaceutical applications. A semi-flow apparatus was used to measure the solubility of gliclazide and captopril in ScCO₂ at 308.2 K, 318.2 K, and 328.2 K within the pressure range of 10.0–18.6 MPa. The newly measured solubility data were correlated and confirmed to be self-consistency with four semi-empirical correlation models: Chrastil, Méndez-Santiago & Teja (MST), Bartle, and Kumar & Johnston (K-J). The newly measured data were then used to evaluate the accuracy of three approaches based on the Peng-Robinson equation of state (PR EOS). PR EOS combining with the Wilson model through the Wong-Sandler mixing rule with two adjustable parameters shown excellent fit with experimental data, while PR EOS combining with the COSMO-SAC model through the MHV1 mixing rule provided reasonable solubility prediction without adjustable parameters.

Graphical Abstract

Introduction

Supercritical fluids have outstanding characteristics of high density, high dissolving power, high diffusivity, low surface tension, and low viscosity. Besides, its solvent power can be easily manipulated by controlling the fluid density via adjusting system temperature and pressure [1]. Due to these advantages, supercritical fluid technology is highly valued in several fields, such as replacing the organic solvents in traditional extraction processes to resolve the issue of residual toxic organic solvents or replacing water in the traditional textile dyeing process to resolve the issue of wastewater treatment. Among all potential supercritical fluids, carbon dioxide has the advantage of a critical temperature (T_c = 304.1 K) close to room temperature and a relatively low critical pressure (P_c = 7.38 MPa), in addition to being easily available, non-flammable, and non-toxic. Therefore, supercritical carbon dioxide (ScCO₂) is considered a green solvent and has been demonstrated for use in several important applications, including fiber dyeing in the textile industry [2], [3], [4], natural compound extraction in the food industry [5], [6], battery electrode manufacturing in the energy industry [7], and crystal morphology and size control in the pharmaceutical industry [8], [9]. Among all these applications, the solubility of the target substances in ScCO₂ is crucial for the design and optimization of relevant processes.

Gliclazide (GLZ) is an oral hypoglycemic drug used for treating type 2 diabetes by promoting insulin secretion from pancreatic β cells to reduce blood glucose. Gliclazide is classified as the second category in the biopharmaceutical classification system (BCS) with low solubility and high permeability. Gliclazide has low water solubility (1.5 μg/ml in distilled water at room temperature [10]), limiting the bioavailability in medical treatment. The application of supercritical fluid technology for recrystallization and micronization of APIs has been a viable way to reduce the crystal size or form a cocrystal with the other coformer or API to enhance its solubility.

Captopril (CAP) is an inhibitor for the angiotensin-converting enzyme; therefore, it can cause vasodilation to lower blood pressure for treating hypertension or congestive heart failure [11]. In addition to the treatment of hypertension, captopril had demonstrated the capability of postponing the development of diabetic nephropathy [12] and has recently been found to enhance the hypoglycemic effect in rat experiments when it was administrated with gliclazide [13]. Contrary to gliclazide, captopril has good solubility in water (160 mg/ml) [14]. Previous studies have demonstrated that the solubility of API can be improved by cocrystallization with a coformer or another API with higher solubility. The dissolution rate and bioavailability of the API may be improved as well [8]. Therefore, gliclazide and captopril might be potential cocrystal candidates for developing a new type of oral drug to treat diabetes and hypertension simultaneously, which are major public health problems and often occur together. However, the feasibility of the cocrystallization of these two APIs and its effectiveness in the human body require further investigation [15]. Nonetheless, the solubility of these two solutes in ScCO₂ is essential information for designing processes containing them using supercritical fluid technology.

In this study, the solubility of gliclazide and captopril in ScCO₂ at 308.2 K, 318.2 K, and 328.2 K in a pressure range of 10.0–18.6 MPa was measured using a semi-flow type apparatus. The newly measured solubility data were then correlated by four semi-empirical models and confirmed to pass the simple consistency test originally proposed by Méndez-Santiago and Teja [16]. Furthermore, thermodynamic models based on the Peng-Robinson equation of state (PR EOS) [17] were employed to correlate the experimental data and the accuracy of a predictive approach of combining PR EOS with the COSMO-SAC model [18], [19] in estimating the solubility of these two solutes in ScCO₂ was examined.

Section snippets

Materials

Gliclazide (C₁₅H₂₁N₃O₃S) and captopril (C₉H₁₅NO₃S) were purchased from Tokyo Chemical Industry (TCI), and the purity of both solid compounds was confirmed to be higher than 99.8% by high-performance liquid chromatography (HPLC), according to the certificate of analysis report (CoA) from TCI. The molecular structure and other information of these two compounds are summarized in Table 1. Carbon dioxide, with a minimum purity of 99.99%, was purchased from Jian Fang Gases Co. Ltd., Taiwan. The

Experimental data

For measuring solid solute solubility in ScCO₂ using a semi-flow apparatus, it is crucial to ensure that the ScCO₂ has sufficient residence time in the equilibrium cells so that the solid solute has sufficient time to dissolve in ScCO₂ to achieve a solute-saturated fluid. A constant solubility under different ScCO₂ flow rates indicates that the supercritical fluid phase was saturated with the solid solute before leaving the equilibrium cell [23]. As shown in Fig. 2, the experimental results for

Conclusion

The solubility of gliclazide and captopril in ScCO₂ was measured with a semi-flow apparatus at 308.2 K, 318.2 K, and 328.2 K in the pressure range of 10–18.6 MPa. Four semi-empirical models were used to correlate the newly measured solubility data and satisfactory correlation results are achieved, indicating self-consistency of newly measured experimental data. Besides, model parameters of the Chrastil and Bartle models were used to estimate the total reaction enthalpy, vaporization enthalpy,

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgment

The authors are grateful to the Ministry of Science and Technology of Taiwan for supporting this study (MOST 106-2221-E-008-088-MY3). The computational resources from the National Center for High-Performance Computing of Taiwan are acknowledged.

References (44)

Ž. Knez et al.
Are supercritical fluids solvents for the future?
Chem. Eng. Process. - Process Intensif.
(2019)
M.T. Abate et al.
Colouration and bio-activation of polyester fabric with curcumin in supercritical CO₂: part II – Effect of dye concentration on the colour and functional properties
J. Supercrit. Fluids
(2020)
H. Zheng et al.
An industrial scale multiple supercritical carbon dioxide apparatus and its eco-friendly dyeing production
J. CO2 Util.
(2016)
J.-J. Long et al.
Investigations on the level dyeing of fabrics in supercritical carbon dioxide
J. Supercrit. Fluids
(2011)
R.H.H. Pinto et al.
Supercritical CO₂ extraction of uxi (Endopleura uchi) oil: Global yield isotherms, fatty acid profile, functional quality and thermal stability
J. Supercrit. Fluids
(2020)
L.C. dos Santos et al.
Solubility of passion fruit (Passiflora edulis Sims) seed oil in supercritical CO₂
Fluid Phase Equilib.
(2019)
I.A. Cuadra et al.
Cocrystallization of the anticancer drug 5-fluorouracil and coformers urea, thiourea or pyrazinamide using supercritical CO₂ as an antisolvent (SAS) and as a solvent (CSS)
J. Supercrit. Fluids
(2020)
B.-C. Wang et al.
Solid solubility measurement of ipriflavone in supercritical carbon dioxide and microparticle production through the rapid expansion of supercritical solutions process
J. CO2 Util.
(2020)
H. Kadin
Captopril
R. Shaikh et al.
Pharmaceutical cocrystal drug products: an outlook on product development
Trends Pharmacol. Sci.
(2018)

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¹: ORCID: 0000-0002-3063-2135

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Measurement and modeling of solubility of gliclazide (hypoglycemic drug) and captopril (antihypertension drug) in supercritical carbon dioxide

Highlights

Abstract

Graphical Abstract

Introduction

Section snippets

Materials

Experimental data

Conclusion

Declaration of Competing Interest

Acknowledgment

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