Pharmacokinetic profile of a sustained-delivery system for physostigmine in rats

Physostigmine (PHY) is involved in clinical treatments of glaucoma, Alzheimerʹs disease and has been suggested as an alternative prophylactic treatment against organophosphate poisoning. However, one of the therapeutic uses of physostigmine is limited by short elimination half-life. In this study, PHY-loaded microparticles, prepared by a spray-drying method with biodegradable poly(d,l-lactide-co-glycolide) (PLGA) with a size ranging from 1 to 5 μM was developed on a sustained release preparation to prevent multiple dosing and yet maintaining constant plasma level. The release of PHY-loaded microparticles was characterized in vitro and in vivo after oral administration in Sprague–Dawley rats. After oral administration of physostigmine-loaded microparticles in rats, the time course of physostigmine in blood plasma was followed over 48 h and samples were analysed using a validated high-performance liquid chromatography (HPLC) assay. In the pharmacokinetics profile of physostigmine for the elimination half-life and area-under-curve, PHY release was sustained in vitro for over 1 week with a low initial burst release. The pharmacokinetics results show a 15-fold increase in the elimination half-life of physostigmine microparticle formulation, coupled with a larger area under the concentration–time curve (AUC), without affecting the peak concentration and the latency to peak concentration, when compared to the standard formulation.