461241 An Investigation into Growth of a Non-Wetting System in High Shear Granulation
Pharmaceutical manufacturing involves different powder ingredients, each with different wetting characteristics. Granulation of non-wetting powders is a common problem which affects granule and tablet uniformity. The discovery of liquid marbles is a promising way to solve the problem of hydrophobic powder wetting behaviour.
The influence of different variables on granule growth behaviour and a qualitative understanding of the granule growth mechanism have been proposed. However the granulation behaviour of a new formulation is still not able to be predicted from knowledge of its basic properties and process parameters.
The aim of this work is to conduct a systematic study of the effect of formulation and operational variables on size distribution and morphology of granules of hydrophobic powder mixtures in high shear granulation. Salicylic acid and microcrystalline cellulose were granulated with Polyethylene glycol 200 in the high shear granulator. Different liquid to solid (L/S) and impeller speed were applied. Granule size distribution and morphology were identified.
The agglomeration behaviour of granules at a low L/S ratio 60/200 was largely unaffected by the impeller speed. As a level of liquid increases, L/S=80/200 - 120/200, there is an increase in granule size as the impeller speed increases from 350 rpm to 450 rpm. However, at 550 rpm impeller speed, there is a small change in the granules size. The granules are spherical at 350 and 450 rpm, and elongated and irregular in shapes at high impeller speed.
At a 60/200 L/S, the particle size distribution is similar to the raw material. However, larger granules appeared at a L/S ratio of 80/200. At a 100/200 L/S ratio, the granule size distribution moved to the right as the granules size increased. Moreover, the amount of un-granulated powder decreased sharply at a L/S 120 with a dramatic increase in granule size to more than 2.5 mm. The granules appeared to be elongated and collapsed with an increase in liquid content.
The effect of impeller speed was found to depend on L/S ratio, although it had little effect on granule size. However, there was much more of effect on the morphology of the granules, especially at high L/S ratio. The effect of L/S was more significant on granule size and shape. As the L/S ratio increases, the amount of un-granulated fine powder of raw materials decreases and the final granule size increases in the size range from 0.3mm to 3mm.