Solubility study of carvedilol in the aqueous mixtures of a choline chloride/propylene glycol deep eutectic solvent

Highlights

• Solubility of carvedilol in choline chloride/propylene glycol deep eutectic solvent + water.

• Correlation/back-calculation of the solubility data by some cosolvency models.

• Calculation of thermodynamic parameters by using the van’t Hoff and Gibbs equations.

Abstract

Solubility behavior of a poorly soluble drug (carvedilol) has been studied in the aqueous mixtures of a deep eutectic solvent composed of choline chloride and propylene glycol at different temperatures (293.15–313.15) K. The obtained solubility data are correlated using some of the well-known cosolvency models such as the van’t Hoff, the mixture response surface, the Yalkowsky, the Jouyban-Acree, the Jouyban-Acree-van’t Hoff, and the modified Wilson models. The accuracy of these mathematical models is investigated with the mean relative deviations of the back calculated solubility data. The apparent thermodynamic properties (i.e. Gibbs energy, enthalpy and entropy) of carvedilol in the investigated mixtures are also calculated with the van’t Hoff and Gibbs equations at T_hm.

Introduction

Carvedilol (CVD, 1-(9H-carbazol-4-yloxy)-3-[2-(2-methoxyphenoxy) ethylamino] propan-2-ol, C₂₄H₂₆N₂O₄, Fig. 1), is a beta blocker drug used for the treatment of mild and severe congestive heart failure [1]. CVD also possesses α₁-adrenoreceptor blocking, vasodilatory and antioxidant activities. This drug shows its action mechanism as a competitive beta blocker at lower concentrations, whereas it is also Ca²⁺ channel antagonist at higher concentrations [2]. This racemic lipophilic aryloxy-propanol amine drug belongs to BCS class II with poor aqueous solubility and low oral bioavailability (25%) [3]. The oral bioavailability of CVD can be improved by increasing its solubility in neat solvents and/or combinations of cosolvents with water. So far, many solubility enhancement techniques like self-emulsifying drug delivery systems [4], [5], [6], cosolvency [7], [8], carrier and complexation [9], [10], [11], [12], enzymes and surfactant [13], ionic liquid formation [14], drug nanoparticle formation [15], solid dispersions [16], [17], [18], nanocrystals [19], [20], and pH adjustment [21] have been developed to improve the solubility of CVD and reported in the literatures. Among them, cosolvency is a simple and the most commonly used technique in the pharmaceutical industry. In this technique, the great difference in polarity of the poorly soluble drug molecules and water being decreased by using water miscible organic solvents [22]. Deep eutectic solvents (DESs) are a new type of green solvents, which are formed between at least two organic compounds (hydrogen bond acceptor (HBA) and a hydrogen bond donor (HBD)). In DESs, quaternary ammonium salt is usually selected as a HBA and it is complexed with an HBD like alcohols, amines, amides or carboxylic acids [23]. DESs have considerable attention owing to their unique physicochemical properties such as thermal stability, low vapor pressure, non-flammability, ease of preparation, normally biodegradable and colorlessness of most of them. Compared to ionic liquids and common organic solvents, DESs are considerably less toxic [24]. Furthermore, DESs have a high solubilization capability especially for poorly water-soluble drugs [25]. Some of reports for using DESs as cosolvent are solubilzation of lamotrigine [26], mesalazine [27], naproxen [28], [29], acetaminophen [30], cefixime [31], and allopurinol [32]. Up to now, there are a few reports on the solubility of CVD in different pure solvent and co-solvency systems [7], [8]. In order to the extension of the database for CVD solubility, we investigated its solubility profile in the aqueous mixtures of a DES as a green solvent. As we know, there is no report for the solubility of CVD in the DES composed of choline chloride (ChCl) and propylene glycol (PG) at different temperatures. The main aim of this research is to determine the solubility of CVD in the ChCl/PG-DES and water at different temperatures (293.15–313.15) K, correlate the experimental solubility data with some mathematical models and calculate thermodynamic parameters for CVD dissolution in these mixtures.