Screening of surfactant mixture ratio for preparation of oil-in-water nanoemulsion: A technical note
In the present work, nanoemulsions were fabricated utilizing the high-energy emulsifcation method. The selection of the ratio of surfactant (tween 80)/co-surfactant (lauroglycol 90) mixtures (Smix) used for the preparation of nanoemulsion was done on the basis of the area occupied by Smix molecules at the interface. Amin at the interface gives the information about the molecules that adsorb at the oil–water interface pack together. The small value of Amin indicates that strong adsorption has taken place at the oil–water interface. Moreover, it indicates a close contact between oil and water too. Molecular orientations of surfactant molecules at this ratio are nearly perpendicular to the interface, providing a more close packing thereby producing a more stable nanoemulsion. A composition that contains different ratios of surfactant (tween 80)/co-surfactant (lauroglycol 90) mixtures (Smix) was prepared to achieve a small Amin value. Surface tension value was used to estimate the area per molecule and surface excess concentration. The value of Amin for Smix ratios 1:0, 1:1, 2:1, 3:1, 4:1, 5:1, 1:2, and 1:3 were found to be 0.83, 0.82, 0.70, 0.62, 0.54, 0.60, 0.86, and 0.87, respectively. Among these Smix ratios, ratio 4:1 was selected for preparing the nanoemulsion as it exhibited the low Amin required for optimum emulsifcation conditions. It can be inferred that the determination of Amin for Smix serves as an effective technique in the screening of Smix ratio for producing a stable
nanoemulsion.
Introduction
Nanoemulsions, stabilized by nanoparticle-sized surfactant molecules, consist of transparent dispersions with oil and water [1,2]. These are kinetically stable systems in which stability is maintained for months [3–6]. Nanoemulsions’ kinetic stability, largely infuenced by droplet size, makes them insensitive to gravitational forces and reduces attractive forces between droplets [5–8]. Moreover, the formulation also does not get destabilized by droplet’s focculation [9].
Surfactants are generally used in the production of nanoemulsions as they lower the interfacial tension between two liquids by getting adsorbed at the interface of oil–water leading to the formation of droplets coated with surfactant; which if further sheared, become interconnected and lead to breaking of droplets into fne ones. As a result of the coating, the movement of oil molecules from the droplet to the bulk aqueous phase is inhibited thereby preventing coalescence or focculation of the droplets.
Surfactants are commonly small-chain fatty acids or alcohols that are soluble in both water and oil. A molecule’s hydrocarbon portion determines its solubility in oil. In contrast, the polar -COOH and -OH groups have an affnity for water that allows a long chain of nonpolar hydrocarbons to dissolve in it. When these molecules are located at an air/water or oil/water interface, the hydrophilic (water-loving) groups may be trapped in the aqueous phase, while the hydrophobic (water-hating) chains can be released. Surface activity is the adsorption, at an interface, of a monomolecular layer (or monolayer) of oriented surfactant. In other words, surface tension at the interface of air and liquid is the free energy essential for the enlargement of the surface per unit area of the solution. When surfactants are added to a liquid system, the surface tension is reduced owing to the adsorption of these molecules as monolayers. Surface excess concentration (Γ) is a quantity of surfactant adsorption at liquid surfaces. This is the excess total of surfactant per unit area of the surface over the amount that would be present if the surfactant concentration were uniform all the way to the surface. More adsorption of surfactant/co-surfactant mixture (Smix) at the interface leads to a reduction in surface tension. When surfactant alone fails to suffciently reduce interfacial tension for nanoemulsion, short-chain co-surfactants are added to achieve near-zero tension. Co-surfactants easily penetrate into the surfactant monolayer and get themselves occupied at empty areas between surfactant molecules resulting in more interfacial fuidity and lowering in bending force of oil– water interface. Therefore, the interfacial flm becomes more fexible, and various flm curvatures are formed, which are later required for nanoemulsion formation. One more objective of adding co-surfactant in formulation is to reduce the amount of surfactant required. The proper selection of co-surfactants and surfactants and the determination of their minimum concentration in a formulation is important.
The impact of surfactants on reducing interfacial tension is crucial for stabilizing oil/water nanoemulsions. As an example, a hydrophobic surfactant in the oil droplet increases the interfacial tension at the interface, while a hydrophilic one reduces it. In contrast, emulsifers with more than one molecule at the interface result in a greater reduction of interfacial tension in comparison to surfactants with only one molecule. Throughout the emulsion system, the temperature exaggerated the reduction of interfacial tension, even though the concept of hydrophilic– lipophilic balance (HLB) number focuses on the surfactant molecule itself, not its interactions with water and oil [10].
In one of the previous studies by Mehta et al.[11], water and diesel nanoemulsion have been prepared where a selection of Smix has been done based on surfactant thermodynamic properties such as minimum surface area per molecule (Amin) and surface excess concentration (Γmax). This approach has been used in other published works also where nanoemulsions have been prepared for a pesticide [12], for water-in-diesel fuel nanoemulsion [13].
For nanoemulsions of drugs, the assortment of cosurfactant and surfactant has been based on the miscibility studies, solubility studies, and HLB value and selection of Smix ratio has been done from the pseudoternary phase diagram in almost all the published works [14–17]. Other criteria that can be used for the selection of Smix ratio are based on surfactant thermodynamic properties such as Amin and Γmax [18]. The value of Amin implies the mean area engaged by each adsorbed molecule at the interface [11]. The smallest Amin and the largest Γ value of surfactant indicates that the surfactants are crammed more closely and adsorbed more powerfully at the interface thus increasing the strength of the interfacial flm and ensuring that the resultant nanoemulsion formed will exhibit greater physical stability.
The formulation of selegiline nanoemulsion has already been published whereby the criteria for the selectionof Smix ratio has been reported on the basis of the construction of a pseudoternary phase diagram [19]. The objective of this paper is to select a ratio of surfactant and co-surfactant for the preparation of nanoemulsion on the basis of Amin value. To the best of our knowledge, the calculation involved in determining the Amin used for selecting Smix ratio has not been reported in detail.
Experimental Section
Materials
A gift sample of selegiline was provided by Sun Pharmaceutical Industries Ltd., New Delhi, India, Lauroglycol 90 from Gattefosse, Saint Priest, Cedex, France and Sefsol 218® from Nikko Chemicals, Tokyo, Japan. Tween 80 was procured from Merck, Mumbai, India, and grape seed oil from Falcon, Bengaluru, India. All other solvents and chemicals used during the experiments were of analytical grade. Screening of Smix on the basis of minimum surface area per molecule (Amin) In the present study, Tween 80 was used as the surfactant and lauroglycol 90 as the co-surfactant. The chemical structures of Tween 80 and lauroglycol 90 are presented in Figure 1.
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Kumar S, Wadhwa K, Pahwa R, Ali J, Baboota S. Screening of surfactant mixture ratio for preparation of oil-in-water nanoemulsion: A technical note. J Appl Pharm Sci. 2024. Online First.
http://doi.org/10.7324/JAPS.2024.180648