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/analgesi c substances was investigated in the presence and absence of different hydr ophobic 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 incr eased from 100 nm to about 4-5 mu m within an hour of manufacture. The addi tion of a small amount of a second component of lower solubility to the dis perse phase decreased the rate of Ostwald ripening, producing good stabilit y 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 emulsion s. The experimentally observed rates of increase in droplet size in the emu lsions were closely correlated with those predicted according to the Liftsh itz-Slezov-Wagner (LSW) theory. (C) 2000 Published by Elsevier Science B.V. All rights reserved.