Preparation of Tiagabine HCl/2-HPβCD Complex Pellets by Extrusion-Spheronization Using Glycerol Monostearate as Pellet-Aid

Glycerol monostearate was used as a pellet-aid to prepare tiagabine HCl/2-HP beta CD inclusion complex pellets (an antiepileptic agent partially included into the 2-HP beta CD cavity to improve its stability). The pellitization of tiagabine HCl/2-HP beta CD inclusion complex (1:1 stoichiometric composition) using 27.3% of melted GMS (60 degrees C) in its liquid form as wetting agent, 30% of microcrystalline cellulose (pellet-forming agent) and 3% of kollidone-30 (binder) was studied. Pellitization was prepared using extrusion/spheronization method. > 80% of pellets, size ranging between 800-1000 m, were obtained indicating a significant pellet yield. The disintegration test of the pellets complied with the Eur. Ph. Limit (0.8%). The TGB pellets formed were better sized and spherically shaped than when GMS was used in its liquid form. Pellets obtained using tiagabine HCl/2-HP beta CD inclusion complex after addition of GMS with very little water content (< 5%) have also a spherical shape, retain their integrity in dissolution medium, which suggested that coatings will not burst prematurely due to granule swelling and release their TGB load rapidly 65-85% in 15min in a phosphate buffered dissolution medium.