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Notes Sedimentation Field-Flow Fractionation Studies of Composition Ripening in Emulsion Mixtures Rebecca A. Arlauskas and Jeffry G. Weers* Alliance Pharmaceutical Corp., 3040 Science Park Road, San Diego, California 92121 Received October 12, 1995. In Final Form: January 9, 1996
Introduction Diffusive mass transport (i.e., Ostwald ripening) has been shown to be the primary mechanism of coarsening in submicrometer fluorocarbon emulsions.1-3 Ostwald ripening occurs in spite of the fact that the solubilities of fluorocarbons in water are on the order of only 10-7 to 10-12 mL/mL.4 Kabalnov et al. have shown that the solubility of the diffusing oil in water is the key parameter in determining the rate of the mass transport process.4 The effect of surfactant micelles in promoting the Ostwald ripening process, although systematic with increasing surfactant concentration, has been shown to be minor.5-9 Perhaps the best experimental evidence for molecular diffusion in fluorocarbon emulsions comes from the socalled “reverse recondensation” experiments performed by Pertsov et al.10 These experiments involve the preparation of two emulsions which differ significantly both in their initial size and in their rate of molecular diffusion. Pertsov et al. were able to show that if the larger sized emulsion was composed of the faster diffusing oil, then molecular diffusion could occur in the “reverse” direction (i.e., from large to small drops).10 Such a disappearance of the large droplet fraction cannot occur by a coalescence process. The driving force for the “composition ripening” process is the free energy gain associated with oil mixing. McClements et al. also examined composition ripening in hexadecane/octadecane emulsion mixtures by monitoring changes in crystallization temperatures of the oils using differential scanning calorimetry (DSC).8,9 They observed increases in the rate of oil exchange by a factor of 5 with increasing micelle concentration. They conclude that the rate of oil exchange is directly proportional to the solubilization capacity of the surfactant. McClements et al. also observed a significant rate of oil exchange, in the absence of micelles. They discuss three possible mechanisms for the nonzero ripening rate in the absence of micelles: (a) not all of the surfactant is present at the oil/water interface, i.e., some remains in micelle form; (b) the oil has a small solubility in water even when no surfactant is present; (c) oil is exchanged during collisions (1) Davis, S. S.; Round, H. P.; Purewal, T. S. J. Colloid Interface Sci. 1981, 80, 508. (2) Kabalnov, A. S.; Shchukin, E. D. Adv. Colloid Interface Sci. 1992, 38, 69. (3) Weers, J. G.; Arlauskas R. A. Langmuir 1995, 11, 474. (4) Kabalnov, A. S.; Makarov, K. N.; Shcherbakova, O. V. J. Fluorine Chem. 1990, 50, 271. (5) Kabalnov, A. S. Langmuir 1994, 10, 680. (6) Taylor, P. Colloids Surf., A 1995, 99, 175. (7) Taylor, P.; Ottewill, R. H. Colloids Surf., A 1994, 88, 303. (8) McClements, D. J.; Dungan, S. R. J. Phys. Chem. 1993, 97, 7304. (9) McClements, D. J.; Dungan, S. R.; German, J. B.; Kinsella, J. E. Colloids Surf., A 1993, 81, 203. (10) Pertsov, A. V.; Kabalnov, A. S.; Kumacheva, E. E.; Amelina, E. A. Kolloidn Zh. 1988, 50, 616.
between droplets. The most likely of these explanations is that the oil has a finite solubility in water even in the absence of micelles.9 In this paper we will examine the effect of the nature of the oil on composition ripening processes via sedimentation field-flow fractionation (SdFFF, FFFractionation, Inc., Salt Lake City, UT). SdFFF utilizes an applied external centrifugal field to order droplets according to their size, with the larger slower diffusing droplets accumulating near the wall of a ribbon-like channel. The ordered array is then subjected to a laminar flow of a mobile phase so that particles near the wall move more slowly compared to those in midstream. This combination of field and flow leads to fractionation of the particles into monodisperse sizes, with the smaller ones exiting the channel first. It is possible to collect fractions of monodisperse particles across the particle size distribution and analyze them by an independent technique. In an earlier study we were able to show the utility of SdFFF coupled with gas chromatography in determining the partitioning of fluorocarbon components between various sized droplets which occurs via molecular diffusion in emulsions containing two disperse phase components.3 Results and Discussion The source, purity, and water solubility of the oils used in the current study are detailed in Table 1. Three pairs of oils were studied. The oil components which were present in the large droplets (i.e., those with the higher water solubility) are shown in boldface. The water solubilities of the diffusing oils vary by approximately 5 orders of magnitude. Thus, significant differences in the rate of composition ripening are expected. Concentrated fluorocarbon emulsions (50-90% (w/v)) were manufactured on a Model M-110 microfluidizer (Microfluidics, Newton, MA) by a method described previously.3 The formulations contained between 2 and 6% (w/v) egg yolk phospholipid (EYP, Pharmacia, Stockholm, Sweden) and the usual complement of salts, buffers, and antioxidants found in pharmaceutical emulsions.3 Composition Ripening in F-66E/PFHB Emulsion Mixtures. Figure 1 shows SdFFF fractograms obtained from a typical composition ripening experiment. Diffusional mass transfer occurs from the large droplets of PFHB (C ) 8 × 10-8 mL/mL, d ) 0.49 µm) to the small F-66E (C ) 1 × 10-12 mL/mL, d ) 0.18 µm) droplets. Here C refers to the water solubility of the fluorocarbon, and d is the mode diameter. The fractogram for the equivolume mixture of the two emulsions shows a disappearance of the larger sized PFHB droplet population near 0.5 µm, and a slight increase in mode diameter (d ) 0.22 µm) with respect to the F-66E droplets. Provided that all of the PFHB emulsion has diffused into the F-66E droplets, the initial diameter for the mixed emulsion system is expected to increase from that obtained for the pure F-66E emulsion by a factor equal to (1 + V1φ1/V2φ2)1/3, where V and φ are the disperse phase volume fraction and volume fraction of emulsion added to the mixture for emulsions 1 and 2, respectively.10 Component 2 is the fast diffusing oil present in the large droplets, i.e., PFHB in this example. Thus, if all of the PFHB droplets were to diffuse into the F-66E droplets in the current experiment, an increase in
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Langmuir, Vol. 12, No. 7, 1996
Notes
Table 1. Source, Purity, and Water Solubility of Oils Used in the Current Study oila
acronym
source
purity, %
water solubility,b (mL/mL)
1,2-bis-F-hexyl ethene F-hexyl bromide F-decyl bromide F-octyl bromide trilinolein triolein
F-66E PFHB PFDB PFOB n.a. n.a.
F-Tech Inc. (Tokyo, Japan) Fluorochem Ltd. (Derbeyshire, U.K.) Atochem (Paris, France) Atochem (Paris, France) Sigma (St. Louis, MO) Sigma (St. Louis, MO)
98.7 98.8 98.9 99.9 ≈99.0 ≈99.0
1 × 10-12 8 × 10-8 2 × 10-11 1 × 10-9
