Effect of Binder Concentration and Method of Addition on Granule Growth in a High Intensity Mixer

A model system consisting of microcrystalline cellulose and povidone was used to study the effect of binder concentration and method of addition on granule growth in a high intensity mixer. The methods of binder addition include blending the dry binder with the excipient prior to granulating with water and granulation of the excipient with an aqueous solution of the binder. When the binder was dry-mixed with excipient prior to wetting, a good correlation was obtained between granule size and binder level. The growth of granules prepared by this method also appears to be related to the mechanical “resistance” encountered by the mixing blade during wet massing. In general, granules prepared by the addition of aqueous binder solutions are smaller than granules prepared with corresponding concentrations of dry binder and demonstrate a lesser degree of granule growth with respect to increasing binder level. For the wet addition method, the mechanical resistance was found to be essentially constant with respect to binder level.