Micronized emulsion for controlled release of physostigmine after oral administration. Part II. Release characteristics and pharmacological evaluation.

In vitro release of physostigmine from an emulsion was more prolonged than from a tablet. This prolongation was attributed to the retention capacity of the dispersed oil droplets. Increase of the oily phase volume ratio from 20 to 50% did not substantially decrease the rate of release, and decrease of the mean oil droplet size did not affect the release profile, indicating that the drug was mainly localized in the external phase of the emulsion. The profiles agreed with those predicted from our earlier mathematical equation based on a three compartment model system. In rabbits there were no significant differences in the Tmax and AUC values obtained by use of a tablet and the emulsion form, but the emulsion form elicited less enzyme inhibition. T20 (the therapeutic occupancy time) was markedly extended following use of the emulsion form.