Stability, disperse and rheological properties of oil-in-water emulsions prepared using poloxamer 188–xanthan gum mixtures

Abstract

Oil-in-water (o/w) emulsions are essential systems in pharmaceutical, cosmetic, and food industries, with an emerging role in tissue engineering and regenerative medicine. In this work, mixtures of poloxamer 188 (P188), a nonionic surfactant with a unique structure and biological properties, and xanthan gum (XG), a well-known natural thickener, were employed for the development of the stable 30% (w/w) sunflower o/w emulsions, with a rotor-stator homogenizer, during the storage period set at 21 days. To evaluate the potential of P188 and XG mixtures to prepare stable emulsions, surface tension properties of their aqueous solutions, creaming stability, disperse, and rheological properties of the emulsions were studied. The investigation of the surface-tension properties indicated that there are no attractive interactions between these compounds. The analysis of the creaming stability during the storage period showed that the addition of XG in concentrations below 0.10% increased gravitational separation, most probably due to the effect of depletion flocculation. The most stable emulsions had XG in concentrations of 0.20% and higher, well above the overlap concentration of the thickener. The droplet size and size distribution analysis, performed 1 and 21 days after the emulsion preparation, showed less significant change in the Sauter mean diameter and size distribution during the storage in emulsions with XG concentrations of 0.20% and higher. The rheological investigations indicated that XG in concentrations above 0.20% yields emulsions with a semi-structured viscoelastic matrix capable of resisting flow, deformation, and creaming. All possible mechanisms involved in the observed phenomena in this work were thoroughly discussed.

Introduction

Oil-in-water (o/w) emulsions are important systems for the pharmaceutical and cosmetic industries. They are easily applied to the skin, can be fine-tuned to provide the desired texture and spreadability, and can carry high amounts of both hydrophilic and lipophilic active compounds, thereby improving drug absorption with good patient acceptability.1–3 The emulsions also have an emerging role in tissue engineering and regenerative medicine.4,5 However, they are inherently unstable because of the immiscibility of the two phases, oil and water, and the density difference between them. To produce o/w emulsions with prolonged stability and optimize their rheological properties, mixtures of emulsifiers and stabilizers, i.e., surfactants and macromolecules, are frequently investigated.6,7

Poloxamer 188 (P188) is a hydrophilic nonionic surfactant with a distinctive structure compared to classic nonionic tensides. It is a triblock copolymer, composed of two hydrophilic polyoxyethylene (PEO) blocks, composed of ethylene oxide (EO) units, flanking a centrally positioned lipophilic polyoxypropylene (PPO) chain having propylene oxide (PO) units (Fig. 1). It has a high hydrophilic–lipophilic balance (HLB) value of 29, an average molar mass of around 8400 g mol−1,8,9 and a high value of critical micelle temperature (CMT) above 36 °C.10,11 P188 is a biocompatible compound, approved by the United States Food and Drug Administration (FDA) as a pharmaceutical and cosmetic excipient,8,9 and an ingredient in over-the-counter products.12 It is listed in both the US and the EU pharmacopoeia.13 In pharmaceutical and cosmetic products, such as micellar solutions, lotions, and creams, poloxamers are primarily used as solubilizers, emulsifiers, and cleansing agents.14–18 The triblock copolymer has been under the research spotlight lately due to its biological properties. Namely, P188 is a well-known membrane stabilizer. It can augment the sealing of cell membranes in various cell types, including muscle cells, fibroblasts, and endothelial cells.19–21 Furthermore, it promotes cell attachment and proliferation, indicating its applicability in tissue engineering, regenerative medicine, and other clinical fields.22

Fig. 1. Schematic structure of poloxamer 188 (P188). Letter x represents the number of repeating ethylene oxide units on both hydrophilic sides of the molecule, while letter y represents the number of repeating propylene oxide units in the central, hydrophobic part of the molecule.

Xanthan gum (XG) is an anionic, water-soluble, branched natural polysaccharide produced by the Xanthomonas bacteria genus, with a molar mass higher than 1 million g mol−1.23 XG is a polyelectrolyte in aqueous solutions, composed of a linear 1,4-linked β-d-glucose backbone, with a negatively charged trisaccharide side chain attached to every other glucose unit of the backbone,24 as shown in Fig. 2. It is a biocompatible compound approved by the FDA as both a food additive and a pharmaceutical excipient,25,26 and is frequently used in cosmetic products.27 In pharmaceutical and cosmetic formulations, such as lotions, creams, and toothpaste, XG is mainly used as a thickener and stabilizer.23,28 The polysaccharide belongs to a group of non-adsorbing macromolecules with high thickening, i.e., viscosity-enhancing, properties.25,29 Due to this, it is used as a stabilizer of various dispersed systems, frequently in mixtures with surface-active compounds.7,24,28 XG can also be used to fine-tune the rheological properties of o/w emulsions. Depending on the concentration, its aqueous solutions show pseudoplastic or even thixotropic behavior.30,31 Its applicability in tissue engineering and regenerative medicine is also investigated.32,33

Fig. 2. Schematic structure of xanthan gum (XG) in aqueous solution. Letter n represents the number of repeating units in the macromolecule.

Sunflower oil was chosen as a model oil since it is commonly used in topical formulations as a non-comedogenic emollient in the pharmaceutical and cosmetic industries.34,35 It contains various bioactive compounds, such as tocopherols, sterols, squalene, and carotenoids, which are beneficial to the skin.36,37 As a biocompatible oil, sunflower oil has shown applicability in tissue engineering.38

Despite the favorable safety profile of P188 and XG, their widespread usage and emerging roles in various industries, the possible interactions between P188 and XG, as well as the applicability of these mixtures in producing stable emulsions, disperse, and rheological properties of such systems, were not investigated, according to the authors’ knowledge. Therefore, the aim of this study was to gain insight into the possible interactions between P188 and XG in aqueous solutions and assess their ability to form o/w emulsions by investigating creaming stability, disperse characteristics, and rheological properties. It is envisioned that the results of this study could provide a better understanding of potential usage of hydrophilic triblock copolymers and XG mixtures in the development of emulsions and to gain more knowledge regarding mechanisms involved in their formation and stabilization, with a broader goal to speed up the development of novel pharmaceutical and cosmetic formulations as well as new matrices for tissue engineering and regenerative medicine applications.

The potential application of the present study and the investigated properties of P188/XG solutions and emulsions with sunflower oil are summarized in Table 1.

Table 1. Required and desirable properties of an emulsifier and a stabilizer system for pharmaceutical, cosmetic, and tissue engineering applications, together with known attributes of poloxamer 188 (P188) and xanthan gum (XG), and the investigated properties of their solutions and the emulsions.

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Materials

Poloxamer 188 (Kolliphor® P 188, LOT number: WPDH566B) with an average molar mass of 8369 g mol−1, according to the certificate of analysis supplied by the producer, was donated by BASF Chemtrade GmbH (Ludwigshafen, Germany). Xanthan gum (Xantural® 180 CP), food grade, with a viscosity of 1561 mPa s for a 1% solution in 1% KCl solution, based on the certificate of analysis provided by the manufacturer, was donated by CP Kelco (Atlanta, GA, USA). Sodium azide was purchased from Sigma-Aldrich (Taufkirchen, Germany, product number: 71290) and was used as an antimicrobial preservative in the aqueous solutions and the emulsions. Sunflower oil produced by Dijamant (Zrenjanin, Serbia), was obtained in the local market. Distilled water was used for the preparation of aqueous solutions and emulsions in the study. All reagents were used without further purification.

Ćirin D, Pavlović N, Nikolić I, Milutinov J, Zaklan D, Atanacković Krstonošić M, Krstonošić V. Stability, disperse and rheological properties of oil-in-water emulsions prepared using poloxamer 188-xanthan gum mixtures. RSC Adv. 2026 Jul 2. doi: 10.1039/d6ra01806h. Epub ahead of print. PMID: 42395713; PMCID: PMC13325336.