Melt pelletization of a hygroscopic drug in a high shear mixer. Part 3. Effects of binder variation

Melt pelletization experiments with sodium valproate as a hygroscopic drug were performed in a laboratory scale high shear miser. In the current part, the effect of altering the binder liquid properties (using different binde rs, varying the temperature, or adding highly dispersed silicon dioxide to the molten binder) on the pellet size, size distribution and the growth rat e was studied. Three meltable binders, namely, glycerol monostearate (GMS), hydrated castor oil (HCO), and polyethylene glycol (PEG), were included in the study. Two series of experiments with GMS or HCO showed a higher granu le growth rate with decreasing binder viscosity. Also, increases in the gra nule growth rate were observed for all meltable binders tested, when the bi nder amount and the impeller speed were increased. Factorial designs with a ll three binders were performed under the same conditions. In these experim ents, no correlation existed between the granule gl on th rate and the visc osity of the different binders. The different granule growth rate, however, was mainly attributed to the different solubility of sodium valproate in t he binder liquid used. Higher solubility increased the volume of the binder liquid and, accordingly, the granule growth rate. Taking the amount of dis solved drug into account, the granule growth rates of GMS and PEG were comp arable. However, HCO displayed a lower granule growth rate, which might be related to its low adhesion tension. During melt pelletization in a high sh ear miser the solubility of the drug in the molten binder strongly influenc es the pelletization process.