Effect of terminal heat sterilization on the stability of phospholipid-stabilized submicron emulsions.
Parenteral emulsions similar in composition to the commercially available fat emulsions were prepared using a Microfluidizer. The relationship of pH and terminal heat sterilization by autoclaving on the stability of phospholipid-stabilized emulsions was evaluated. The stability of these formulations was determined by using droplet size and zeta potential measurements. It was found that the zeta potentials of emulsions stabilized by more purified phospholipid were lower in magnitude compared to those stabilized by less purified phospholipid. Furthermore, acidic emulsions (between pH 5.0 and 7.0) showed an increased droplet size upon autoclaving, whereas the emulsions adjusted to an alkaline pH (pH 8.0 to 10.0) did not show a significant change in their droplet sizes upon autoclaving. The zeta potentials of all the emulsions "increased" (in magnitude) upon autoclaving and achieved values between -40 and -50 mV. The results of our studies could be explained on the basis of hydrolysis of phosphatidylcholine at different pH values, leading to a breakdown of the film surrounding the oil droplet, which results in coalescence and/or cracking of the emulsions.
Chaturvedi
P R
PR
Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Morris Plains, NJ 07950.
Patel
N M
NM
Lodhi
S A
SA
D004355:Drug Stability; D004655:Emulsions; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D010743:Phospholipids / Q000737:chemistry*; D013242:Sterilization
D004655:Emulsions; D010743:Phospholipids