Crosslinking of drug–alginate granules: Part 2. Effect of granule preparation and composition on granule properties

Abstract

Paracetamol–alginate (Keltone HVCR) (1:1) granules were prepared by a wet granulation process followed by crosslinking of dried granules in calcium chloride solution. The effect of shear (planetary (low), Brabender (high)), binder quantity (1:2, 1:1 water:powder) and drug particle size (PS 98, 275 μm) were studied using a factorial design. Supporting studies were carried out varying binder quantity and alginate grade (viscosity). In the pre-treated granules, drug entrapment was mainly influenced by drug PS, where the smaller particles showed better embedding. After crosslinking, drug particle size continued to be the most important factor influencing drug recovery. All factors influenced early stage release where high shear, high binder, small drug PS granules showed least release and the low shear, low binder and large drug PS granules showed greatest release. Some significant two-factor interactions were found. Granule consolidation (shown by SEM) and particle embedding increased with binder quantity and reduced as the alginate viscosity was increased. Crosslinking, as shown by Na and Ca contents was >90%. The impact of granule consolidation on drug entrapment and recovery was relatively small (<10%) when compared to its effect on early stage drug release (>60%) which may be important if these granule systems are to be used for taste improvement.