Other Factors that Affect Emulsion Stability

There are several other factors that, if not controlled rigorously, can affect emulsion stability. These were investigated in detail with the emulsion used for clinical trials in prostate cancer patients, i.e., 1 mL of 100mM phospholipid

Emulsion Stability
Figure 6 Effect of total liposomal phospholipid concentration on the stability of liposomal oil-in-water emulsions. Liposomes containing various amounts of phospholipids were emulsified with 40% light mineral oil. The amount of separation was measured as a function of time.
Emulsion Stability
Figure 7 Effect of different amounts of light mineral oil on emulsion stability. Liposomes containing 100 mM phospholipids were emulsified with the percentage of oil indicated. The amount of separation was measured as a function of time.

liposomes containing 100 mg PSA and 200 mg of lipid A emulsified with 0.1 mL of light mineral oil as per the process described above. As stated above, the emulsion starts to break after eight hours of incubation at room temperature. The factors investigated include:

1. Syringe—Changing from 3-mL glass syringes (Hamilton Company) to B-D Glaspak syringes (glass barrels with plastic plungers containing rubber ends; Becton Dickinson, Franklin Lakes, New Jersey, U.S.A. cat. no. 5291) or B-D 3-mL plastic syringes had no effect on emulsion stability. The Glaspak syringe does not contain a luer-lock connector and the syringe can easily come off of the stopcock, especially at high oil concentrations, during the emulsion process.

2. Bore size of the stopcock—If the stopcock bore size was reduced from 0.1-0.05 cm, the emulsion did not break even at 10 hours. However, it was broken within 24 hours after emulsification. The use of the 0.05-cm bore stopcock increased the shear force during emulsification, thus increasing emulsion stability. However, the decrease in bore size made it difficult to push the solution through the stopcock when making the emulsion. When a 0.22-cm bore stopcock was used, the resulting emulsion broke in three hours. The large bore size caused a reduced shear force during emulsification, thus decreasing emulsion stability.

3. Pass rate during emulsification—Decreasing the pass rate from 2 passes/sec to 0.5 or 1 pass/sec dramatically reduced the stability of the emulsion. The emulsion broke at 0.25 and 0.5 hour, respectively, for the 0.5 and 1 pass/sec emulsion rate. Increasing the pass rate beyond 2 passes/sec is not physically possible when making the emulsion by hand.

4. Duration of the emulsion process—When the time of emulsification was decreased from five minutes to 30 seconds only minimal emul-sification was obtained. There was a detectable phase separation 15 minutes after completion of the process. At the first and second minute, the emulsion broke at 0.5 and third hour, respectively. In contrast, there was no difference observed in the emulsion stability between the third and fifth minute of emulsification.

5. Protein encapsulated in the liposome—Liposomal emulsions made with liposomes lacking protein antigen have greater stability. An emulsion made with 10% light mineral oil and 100 mM phos-pholipid liposomes lacking protein antigen was stable for at least 24 hours, but started to break by 48 hours. The same emulsion made with PSA-encapsulated liposomes broke by eight hours. In addition, there are differences in emulsion stability based on the antigen encapsulated in the liposomes used to make the emulsion.

As described above, an emulsion containing PSA encapsulated in 150 mM phospholipid liposomes emulsified with 40% light mineral oil was stable for three years. In contrast, when the same emulsion was made with liposome encapsulated anthrax protective antigen, the emulsion broke after one month of incubation at 4°C. Interestingly, the formation of a cream layer during emulsion breakdown occurred only when antigen was present (Fig. 5B and C). Creaming does not occur with all antigens and predominately appears when high liposomal phospholipids concentrations are emulsified with higher percentages of light mineral oil.

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  • Bilba
    How emulsions are made stable?
    8 years ago
  • ONNI
    How amount of oil affect emulsion stability?
    7 years ago
  • PEONY
    What are the factors that affec the stability of emulsion?
    7 years ago
  • Dodinas
    Which factor affect to make good emulsion?
    3 years ago

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