Langmuir 1997, 13, 5249-5251
5249
Preparing Nontoxic Microemulsions. 2 M. Kahlweit,* G. Busse, and B. Faulhaber Max-Planck-Institut fu¨ r Biophysikalische Chemie, Postfach 2841, D-37018 Go¨ ttingen, Germany Received June 4, 1997. In Final Form: July 17, 1997X
In two Letters published earlier in this journal, we have presented recipes for preparing nontoxic microemulsions with unsaturated fatty acid alkyl esters, biological amphiphiles, and alkane-1,2-diols as cosolvents. In this paper we summarize the results and add some new ones, using a saturated fatty acid ester (isopropyl myristate), as well as an essential oil (orange oil).
Introduction The preparation of microemulsions with mineral oils, synthetic amphiphiles, either ionic or nonionic, andsif necessarysn-alkanols as cosolvents, has become a wellestablished practice.1 Because, however, mineral oils and synthetic amphiphiles, as well as alkanols are, in general, harmful, the problem arises how to prepare microemulsions with nontoxic oils, amphiphiles, and cosolvents for possible applications in pharmaceutical industry. As for nontoxic biological amphiphiles, we have found Epikuron 200 (L. Meyer, Hamburg),2 which is an inexpensive mixture of long-chain soy bean lecithins, (C16-18)2PC, with unsaturated carbon chains, and APG 600 (Henkel),3 which is an inexpensive β-D-alkyl polyglucoside, C12-14G1.3, being practically equivalent to the expensive monoglucoside C12G1, to be rather efficient emulsifiers for mineral oils. Because Epikuron is more soluble in oil than in water (2), one has to add a watersoluble alkanol such as propanol as cosolvent for enforcing a 2 f 3 f 2 inversion.4 APG 600, on the other hand, is more soluble in water than in oil (2), so that one has to add an oil-soluble alkanol such as pentanol as cosolvent for enforcing a 2 f 3 f 2 inversion.5 Searching for nontoxic cosolvents, we then found that alkanols can readily be replaced by the nontoxic alkane-1,2-diols, in particular, propanol by the water-soluble pentane-1,2diol, and pentanol by the oil-soluble octane-1,2-diol. We have, hence, used the two combinations, Epikuron 200/ pentane-1,2-diol (C5-diol) and APG 600/octane-1,2-diol (C8diol), as emulsifiers, with the latter being, in general, a little less efficient than the first one. Another disadvantage of the APG 600 lies in the fact that it is supplied as 50 wt % solution in water, which rules out the preparation of microemulsions with high oil/water ratios. We emphasize that one has to use 1,2-diols because the other diols are much less surface active. This can be readily demonstrated by comparing the reduction of the surface tension σ of the water/air interface by octane-1,2-diol with that by octane-1,8-diol. While with the 1,2-diol, σ drops steeply to 29 mJ m-2 at the solubility limit, with the 1,8diol it drops to only 49 mJ m-2. X Abstract published in Advance ACS Abstracts, September 1, 1997.
(1) See, e.g.: Kahlweit, M. J. Phys. Chem. 1995, 99, 1281. (2) Kahlweit, M.; Busse, G.; Faulhaber, B. Langmuir 1995, 11, 1576. (3) Kahlweit, M.; Busse, G.; Faulhaber, B. Langmuir 1995, 11, 3382. (4) Shinoda, K.; Kaneko, T. J. Dispersion Sci. Technol. 1988, 9, 555. (5) Kahlweit, M.; Busse, G.; Faulhaber, B.; Eibl, H. Langmuir 1995, 11, 4185.
S0743-7463(97)00583-0 CCC: $14.00
Figure 1. Sections through the phase tetrahedron of the quaternary mixture H2O-IPM-Epikuron-pentane-1,2-diol in rectangular coordinates: left, at 40 °C and various oil/water ratios R; right, dependence on temperature (top and bottom) and on brine concentration (center) at fixed R ) 50 wt %.
We, furthermore, note that Findenegg and co-workers6 have recently studied the applicability of the combination octy monoglucoside/geraniol (trans-3,7-dimethyl-2,6-octadien-1-ol) as emulsifier. However, when comparing the efficiency of this combination with that of APG 600/octane1,2-diol, we found the latter to be more efficient. Isopropyl Myristate. As for nontoxic biological oils, we have performed our earlier experiments with unsaturated fatty acid alkyl esters, in particular, oleic acid ethyl ester (OAEE), and the inexpensive rape oil methyl ester (RME, sold in Germany as “bio-diesel”). Because, however, these unsaturated oils are sensitive to both light and oxygen, we searched for more stable saturated esters as oils. As such we first studied the applicability of myristic (6) Stubenrauch, C.; Paeplow, B.; Findenegg, G. H. Langmuir 1997, 13, 3652.
© 1997 American Chemical Society
5250 Langmuir, Vol. 13, No. 20, 1997
Kahlweit et al.
Figure 2. As in Figure 1 with APG 600 and octane-1,2-diol as emulsifyers. Because APG 600 is supplied as 50 wt % solution in water, the upper left R ) 75 wt % diagram had to be omitted.
Figure 3. As in Figure 1 with orange oil (Rotihistol) as oil.
acid isopropyl ester (isopropyl myristate, IPM). Figure 1 shows sections through the phase tetrahedron of the mixture H2O-IPM-Epikuron-C5-diol at fixed temperatures in rectangular instead of triangular coordinates. The abcissa gives the mass fraction γ
γ≡ amphiphile/(water + oil + amphiphile)
in wt %
of the amphiphile in the ternary mixture, the ordinate, δ, is that of the diol in the quaternary mixture.
δ≡ diol/(water + oil + amphiphile + diol)
in wt %
The left column shows the “fish” at various ratios R between oil and water
R ≡ oil/(water + oil)
in wt %
at 40 °C, and the right column shows the dependence of the position of the R ) 50 wt % fish on temperature (top and bottom) and the mass fraction (in wt %) of NaCl in water (center). As one can see, the effect of both temperature and brine concentration is weak. As for the experimental procedure, the following has turned out to be the most convenient one: First dissolve the desired mass of Epikuron (γ) in the oil at about 60 °C. Then add the desired mass of water (R) and lower the temperature to the desired temperature. Finally, add the desired mass of the cosolvent (δ). The mixtures are, in general, of low viscosity, and separate rather rapidly into the various phases. With APG 600, first dissolve the amphiphile in water and then add the oil. In some cases, the ternary mixtures are rather viscous but become fluid upon adding the cosolvent, again separating rather rapidly. Figure 2 shows the corresponding results for the mixture H2O-IPM-APG 600-C8-diol. The upper left diagram is blank becausesas mentioned abovesAPG 600 is supplied as 50 wt % solution in water which does not permit
Figure 4. As in Figure 3 with APG 225 and octane-1,2-diol as emulsifyers. APG 225 is supplied as 65 wt % solution in water which permits preparing mixtures with R ) 75 wt % (upper left).
preparing water in oil emulsions at R ) 75 wt %, so that for preparing microemulsions at high oil/water ratios one would have to use the more expensive “dry” C12G1. As one can see, the combination APG 600/C8-diol is indeed less efficient than Epikuron/C5-diol (Figure 1). Orange Oil We then turned to essential oils. As first example we used a terpene-free orange oil (supplied as Rotihistol by Roth, Karlsruhe, as substitute for xylene for histological
Preparing Nontoxic Microemulsions
preparations). Figure 3 shows the results for the mixture H2O-Rotihistol-Epikuron-C5-diol. We note that if the experiments are performed with “terpene-poor” orange oil (also supplied by Roth), the results differ only little. An attempt to emulsify Rotihistol with APG 600 failed. We, therefore, substituted APG 600 by the more hydrophilic APG 225 (Henkel, C8-10G1.3, being practically equivalent to C8G1). Because APG 225 is supplied as 65% solution in water, it does permit preparing microemulsions with R ) 75 wt %. Figure 4 shows the results.
Langmuir, Vol. 13, No. 20, 1997 5251
Further experiments with other essential oils such as caraway, lavender, and pine oil are in progress. Since all these oils vary in structure and, hence, in polarity or, rather, nonpolarity, each oil requires a particular combination of amphiphile and cosolvent. With these experiments we hope to widen the selection of nontoxic microemulsions for possible applications in the chemical and pharmaceutical industry. LA970583Z
