Temperature Effect on the Adsorption and Volumetric Properties of Aqueous Solutions of Kolliphor® ELP

Density, viscosity and surface tension of Kolliphor^® ELP, the nonionic surfactant aqueous solutions were measured at temperature T = 293–318 K and at 5K interval. Steady-state fluorescence measurements have been also made using pyrene as a probe. On the basis of the obtained results, a number of thermodynamic, thermo-acoustic and anharmonic parameters of the studied surfactant have been evaluated and interpreted in terms of structural effects and solute–solvent interactions. The results suggest that the molecules of studied surfactant at concentrations higher than the critical micelle concentration act as structure makers of the water structure.

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Introduction

Considering the landscape of current drug development, it can be stated, that 40% of NCE (new chemical entities) are characterized by poor water solubility [1]. Therefore, there is a need for excipients to solubilize such candidates in both the early preclinical and clinical evaluation, as well as for the development of the marketed drug dosage forms. Solubilization is the process of drug uptake through complex formation into, e.g., oligomers of dextrose and fatty acids, through the cosolvent systems (such as ethanol, polyethyleneglycol and glycerol), or through the surfactant systems [2]. Contrary to the expectation that pharmaceutical excipients are pharmacologically inactive, there is abundant evidence that they can influence drug metabolism and efflux transport [3,4,5]. Some surfactants, particularly nonionic Kolliphors which were known earlier as Cremophors, find application in pharmaceutical formulations as the forms of solid dosage and delivery systems based on lipids aimed at improvement of poorly water-soluble drugs bioavailability [2,6]. The triricinoleate ester of ethoxylated glycerol is the main component of Kolliphors. The others are polyethylene glycol ricinolates, as well as the corresponding free glycols [7]. Kolliphor^® EL (EL), being the most often used Kolliphor, was applied as a vehicle in the case of solubilization of some hydrophobic drugs, including cyclosporin A, diazepam, propofol and paclitaxel [8]. However, some researchers stated that EL is not an inert vehicle but exerts a range of biological effects, some of which have important clinical implications. Its use was associated with severe anaphylactoid hypersensitivity reactions, hyperlipidemia, abnormal lipoprotein patterns, aggregation of erythrocytes and peripheral neuropathy. The pharmacokinetic behavior of EL is dose-independent, although its clearance is highly influenced by the duration of the infusion [9,10]. This is particularly important since EL can affect the disposition of various drugs by changing the unbound drug concentration through micellar encapsulation. From this point of view, a clear understanding of the biological and pharmacological role of surfactants is essential to help oncologists avoid side-effects associated with the use of paclitaxel or other agents. On the other hand to describe the behavior of surfactants in relation to two non-miscible phases and the range of temperatures at which they are active, some adsorption and volumetric properties of the solution of such surfactants are needed. Thus, the purpose of the presented studies was to determine some adsorption, volumetric, thermo-acoustic as well as anharmonic properties of aqueous solutions of Kolliphor^® ELP (ELP), a purified grade of EL, by surface tension, density and viscosity measurements at T = 293–318 K with 5 K interval. Moreover, the properties of the solutions were studied by means of steady-state fluorescence measurements. Based on the results, the analysis was applied to study different molecular interactions in the solutions taking into account the change of these properties depending on concentration and temperature.

Article information: Szymczyk, K.; Szaniawska, M.; Krawczyk, J. Temperature Effect on the Adsorption and Volumetric Properties of Aqueous Solutions of Kolliphor^®ELP. Molecules 2020, 25, 743. https://doi.org/10.3390/molecules25030743

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