Inhibition of Ostwald ripening in local anesthetic emulsions by using hydrophobic excipients in the disperse phase.
The stability of submicron emulsions of different local anesthetic/analgesic substances was investigated in the presence and absence of different hydrophobic excipients (ripening inhibitors). Ostwald ripening was believed to be the underlying mechanism for the instability of these emulsions. In the absence of ripening inhibitors, the mean droplet size of the emulsions increased from 100 nm to about 4-5 microm within an hour of manufacture. The addition of a small amount of a second component of lower solubility to the disperse phase decreased the rate of Ostwald ripening, producing good stability of the emulsions. The efficiency of the ripening inhibitors was directly proportional to their solubility in the disperse phase, i.e. the water. The lower the solubility, the more effective the stabilization of the emulsions. The experimentally observed rates of increase in droplet size in the emulsions were closely correlated with those predicted according to the Liftshitz-Slezov-Wagner (LSW) theory.
Welin-Berger
K
K
AstraZeneca, SE-151 85, Södertälje, Sweden.
Bergenståhl
B
B
D000779:Anesthetics, Local / Q000737:chemistry*; D004058:Diffusion; D004655:Emulsions / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry*; D007700:Kinetics; D008012:Lidocaine / Q000737:chemistry; D008956:Models, Chemical; D010316:Particle Size; D011318:Prilocaine / Q000737:chemistry; D012995:Solubility
D000779:Anesthetics, Local; D004655:Emulsions; D005079:Excipients; D011318:Prilocaine; D008012:Lidocaine