The aim of this work was to investigate the phase behaviour and the structure of the n-hexane/water emulsions based on a nonionic, nontoxic and biocompatible surfactant, Tween 80. This system is of interest for new pharmaceutical techniques based on supercritical fluids to form nano- and encapsulated particles. However, it showed a lack of stability denoted by large areas of macroemulsion. For this reason, the effect of additives (alcohols and brine) and external variables (temperature) were explored. The replacement of water by brine caused negligible impact due to the nonionic character of Tween 80. On the contrary, the presence of an alcohol (ethanol or 1-butanol) enhanced the solubility of the surfactant in the oil phase and decreased the mixture viscosity, resulting in improved surface activity. Similar results were obtained by raising the temperature until the cloud point was reached (60°C). With these modifications, microemulsions at relatively low concentrations of surfactant (around 30%) and within a broad interval of compositions could be obtained, widening their possible use in pharmaceuticals manufacturing (such as controlled drug delivery, enzymatic reactions, or excipient processing). The understanding of the surfactant performance could be further used to substitute the n-hexane by a greener solvent, such as supercritical CO2. 1. Introduction Under the principles of sustainable development and being environmentally friendly, a new field, called green chemistry, has been developed based on waste minimisation, energy efficiency, nonhazardous raw materials, solvents or products, inherently safe chemicals processes, and on renewable feedstocks [1]. In this sense, the global pharmaceutical corporations have encouraged the integration of green chemistry and green engineering into the pharmaceutical industry [2]. Between the key research areas for sustainable manufacturing, emulsions have generated a lot of interest, due to the fact that many pharmaceutical processes include direct or indirect contact with some kinds of emulsions in some of their innumerable applications. The term emulsion designates a system composed of two immiscible liquids, one dispersed in the other, in a more or less stable way [3]. It is possible to make these two liquids compatible so that the mixture could be manipulated, administered, and used without breaking. The general structure of emulsions comprises one phase formed by water or a water solution and another phase formed by an organic solvent insoluble in water, which is known as oil. Such emulsions are usually of
References
[1]
M. Lancaster, “Principles of sustainable and green chemistry,” in Handbook of Green Chemistry and Technology, J. Clark and D. Macquarrie, Eds., pp. 10–27, Blackwell Science, Oxford, UK, 2002.
[2]
D. J. C. Constable, P. J. Dunn, J. D. Hayler et al., “Key green chemistry research areas—a perspective from pharmaceutical manufacturers,” Green Chemistry, vol. 9, no. 5, pp. 411–420, 2007.
[3]
G. Barnes and I. Gentle, Interfacial Science: An Introduction, Oxford University Press, 2005.
[4]
K. Shinoda and B. Lindman, “Organized surfactant systems: microemulsions,” Langmuir, vol. 3, no. 2, pp. 135–149, 1987.
[5]
Y.-Y. Luk and N. L. Abbott, “Applications of functional surfactants,” Current Opinion in Colloid and Interface Science, vol. 7, no. 5-6, pp. 267–275, 2002.
[6]
B. A. Kerwin, “Polysorbates 20 and 80 used in the formulation of protein biotherapeutics: structure and degradation pathways,” Journal of Pharmaceutical Sciences, vol. 97, no. 8, pp. 2924–2935, 2008.
[7]
B. K. Paul and S. P. Moulik, “Microemulsioins: an overview,” Journal of Dispersion Science and Technology, vol. 18, no. 4, pp. 301–367, 1997.
[8]
S. P. Moulik and B. K. Paul, “Structure, dynamics and transport properties of micro emulsions,” Advances in Colloid and Interface Science, vol. 78, no. 2, pp. 99–195, 1998.
[9]
S. P. Moulik and A. K. Rakshit, “Physicochemisty and applications of microemulsions,” Journal of Surface Science and Technology, vol. 22, no. 3-4, pp. 159–186, 2006.
[10]
C. T. Lee Jr., W. Ryoo, P. G. Smith Jr. et al., “Carbon dioxide-in-water microemulsions,” Journal of the American Chemical Society, vol. 125, no. 10, pp. 3181–3189, 2003.
[11]
M. Haruki, K. Matsuura, Y. Kaida, S.-I. Kihara, and S. Takishima, “Microscopic phase behavior of supercritical carbon dioxide + non-ionic surfactant + water systems at elevated pressures,” Fluid Phase Equilibria, vol. 289, no. 1, pp. 1–5, 2010.
[12]
W. Peter Wuelfing, K. Kosuda, A. C. Templeton, A. Harman, M. D. Mowery, and R. A. Reed, “Polysorbate 80 UV/vis spectral and chromatographic characteristics—defining boundary conditions for use of the surfactant in dissolution analysis,” Journal of Pharmaceutical and Biomedical Analysis, vol. 41, no. 3, pp. 774–782, 2006.
[13]
H. Kahl, K. Quitzsch, and E. H. Stenby, “Phase equilibria of microemulsion forming system n-decyl-β-D-glucopyranoside/water/n-octane/1-butanol,” Fluid Phase Equilibria, vol. 139, no. 1-2, pp. 295–309, 1997.
[14]
J. L. Salager, L. Márquez, I. Mira, A. Pe？a, E. Tyrode, and N. B. Zambrano, “Principles of emulsion formulation engineering,” in Adsorption and Aggregation of Surfactants in Solution, K. L. Mittal and D. O. Shah, Eds., vol. 109 of Surfactant Science Series, pp. 501–524, Marcel Dekker, New York, NY, USA, 2002.
[15]
D. G. Peck and K. P. Johnston, “Theory of the pressure effect on the curvature and phase behavior of AOT/propane/brine water-in-oil microemulsions,” Journal of Physical Chemistry, vol. 95, no. 23, pp. 9549–9556, 1991.
[16]
M. Kahlweit, R. Strey, and G. Busse, “Microemulsions: a qualitative thermodynamic approach,” Journal of Physical Chemistry, vol. 94, no. 10, pp. 3881–3894, 1990.
[17]
M. Porras, C. Solans, C. González, A. Martínez, A. Guinart, and J. M. Gutiérrez, “Studies of formation of W/O nano-emulsions,” Colloids and Surfaces A, vol. 249, pp. 115–118, 2004.
[18]
D. Attwood and A. T. Florence, Surfactant Systems. Their Chemistry, Pharmacy and Biology, Chapman and Hall, New York, NY, USA, 1983.
[19]
S. Reekmans, H. Luo, M. Van Der Auweraer, and F. C. De Schryver, “Influence of alcohols and alkanes on the aggregation behavior of ionic surfactants in water,” Langmuir, vol. 6, no. 3, pp. 628–637, 1990.
[20]
Y. Bayrak and M. Iscan, “Studies on the phase behavior of the system non-ionic surfactant/alcohol/ alkane/H2O,” Colloids and Surfaces A, vol. 268, no. 1–3, pp. 99–103, 2005.
[21]
A. Yaghmur, A. Aserin, and N. Garti, “Phase behavior of microemulsions based on food-grade nonionic surfactants: effect of polyols and short-chain alcohols,” Colloids and Surfaces A, vol. 209, no. 1, pp. 71–81, 2002.
[22]
J. Sj？blom, R. Lindberg, and S. E. Friberg, “Microemulsions—phase equilibria characterization, structures, applications and chemical reactions,” Advances in Colloid and Interface Science, vol. 65, pp. 125–287, 1996.
[23]
W. Warisnoicharoen, A. B. Lansley, and M. J. Lawrence, “Nonionic oil-in-water microemulsions: the effect of oil type on phase behaviour,” International Journal of Pharmaceutics, vol. 198, no. 1, pp. 7–27, 2000.
[24]
S. Ajith and A. K. Rakshit, “Effect of NaCl on a nonionic surfactant microemulsion system,” Langmuir, vol. 11, no. 4, pp. 1122–1126, 1995.
[25]
H. Coulombeau, F. Testard, T. Zemb, and C. Larpent, “Effect of recognized and unrecognized salt on the self-assembly of new thermosensitive metal-chelating surfactants,” Langmuir, vol. 20, no. 12, pp. 4840–4850, 2004.
[26]
H. Schott, “Salting in of nonionic surfactants by complexation with inorganic salts,” Journal of Colloid And Interface Science, vol. 43, no. 1, pp. 150–155, 1973.
[27]
P. Mukherjee, S. K. Padhan, S. Dash, S. Patel, P. K. Mohapatra, and B. K. Mishra, “Effect of temperature on pseudoternary system Tween-80-butanol-hexane-water,” Journal of Colloid and Interface Science, vol. 355, no. 1, pp. 157–163, 2011.
[28]
S. Y. Shiao, V. Chhabra, A. Patist et al., “Chain length compatibility effects in mixed surfactant systems for technological applications,” Advances in Colloid and Interface Science, vol. 74, no. 1–3, pp. 1–29, 1998.
[29]
J. L. Salager, “Phase transformation and emulsion inversion on the basis of catastrophe theory,” in Encyclopedia of Emulsion Technology, P. Becker, Ed., vol. 3 of Basic Theory Measurement Applications, pp. 79–134, Marcel Dekker, New York, NY, USA, 1988.
[30]
F. Podlogar, M. Ga？perlin, M. Tom？i？, A. Jamnik, and M. B. Roga？, “Structural characterisation of water-Tween 40/Imwitor 308-isopropyl myristate microemulsions using different experimental methods,” International Journal of Pharmaceutics, vol. 276, no. 1-2, pp. 115–128, 2004.
[31]
P.-C. Wu, Y.-H. Lin, J.-S. Chang, Y.-B. Huang, and Y.-H. Tsai, “The effect of component of microemulsion for transdermal delivery of nicardipine hydrochloride,” Drug Development and Industrial Pharmacy, vol. 36, no. 12, pp. 1398–1403, 2010.
[32]
S. Hoeller, A. Sperger, and C. Valenta, “Lecithin based nanoemulsions: a comparative study of the influence of non-ionic surfactants and the cationic phytosphingosine on physicochemical behaviour and skin permeation,” International Journal of Pharmaceutics, vol. 370, no. 1-2, pp. 181–186, 2009.
[33]
A. Azeem, Z. I. Khan, M. Aqil, F. J. Ahmad, R. K. Khar, and S. Talegaonkar, “Microemulsions as a surrogate carrier for dermal drug delivery,” Drug Development and Industrial Pharmacy, vol. 35, no. 5, pp. 525–547, 2009.
[34]
K. Holmberg, B. J？nsson, B. Kronberg, and B. Lindman, Surfactants and Polymers in Aqueous Solution, John Wiley & Sons, 2002.
[35]
H. P. Mishra, N. Jyotish, S. Panigrahi, and P. K. Misra, “Organization of amphiphiles, part IX: effect of molecular structure of cosurfactants and oils on the phase behavior of tween-80: alkanol-oil-water systems,” Journal of Dispersion Science and Technology, vol. 30, no. 4, pp. 564–574, 2009.
