Galantamine Development Of Sustained Release Suspensions

Galanthamine (GAL) is a second-generation inhibitor of the acetylcholine-esterase (AChE), mainly for Alzheimer's disease. There are several kinds of dosage forms such as tablets, capsules and oral solutions for GAL, but these dosage forms should be administrated 3 or 4 times daily. We designed a GAL sustained-release suspensions which prepared with the technologies both the ion-exchange adsorption and the modification of the surface of GAL-resin.GAL was adsorbed by sodium polystyrene sulfonate cationic exchange resin to form GAL-resin, then the residue-SO₃^- groups on the surface of GAL-resin were ion bonded with the NH₄⁺ groups of Eudragit RS100, so that the surface of GAL-resin be covered with the long chain of Eudragit RS100.The pharmacokinetic behavior of GAL in plasma and brain tissue of mice were similar. The concentration of GAL in brain was 2.62-fold compared with in plasma after oral administration. The pharmacokinetic parameters for GAL sustained release suspensions and solutions in rat after oral administration were as follow: C_max: 209.05 ng/ml and 333.16ng/ml, T_max: 4.5 h and 1.4 h, T_1/2: 12.55 h and 7.05h, AUC: 2555.67 ng·h/ml and 2007.78 ng·h/ml, the absolute bioavailability: 55.80% and 43.84%, respectively. Compared with GAL solutions, the relative bioavailability of sustained-release suspensions was 127.29%, that suggested the GAL released from ion-exchange was in the ion state, which may be a kind of "active state" and more easily be absorbed.The relationship between AChE inhibition of GAL and the concentration of GAL in mice brain was studied in this article. After the GAL was absorbed into the brain tissue it can quickly decrease the brain AChE level of mice, and the maximum inhibition activity of AChE were 0.25h to 0.5h after administration.