(67g) High Shear Wet Granulation of a Lubricated Pharmaceutical Formulation

Granulation plays an important role in pharmaceutical manufacturing as a common process in a solid dosage production line. Usually, excipients and active ingredients undergo this process to enhance the flow properties of the material in the compaction stage. Among the excipients, lubricants are widely used to enhance the compression efficiency, however, most of them modify the hydrophobicity of pharmaceutical formulations, which can alter significantly the process and the final product.

In this work, the effect of the concentration of lubricant in a high shear granulation process was evaluated experimentally. A lactose-based placebo formulation was prepared using magnesium stearate as lubricant at two different concentrations (1% and 3% w/w) and the granulation performance was compared with a non-lubricated formulation. A diluted polyvinylpyrrolidone (PVP) solution was used as binder.

Lubricant dispersion at different times was estimated by a hydrophobicity measurement based on the Washburn equation according to the procedure described by Llusa et al. in 2010 [Powder Technology, 198 (2010) 101-107]. The evolution of the particle size of the material in the massing stage was monitored off line by means of standard laser diffraction for fine particles (< 1mm) and standard sieving test for coarse granules (>1mm). Liquid content distributions were also determined by loss on drying method, while geometric and physical characteristics of the granules can be observed in scanning electron microscope images.

Results indicate quantitatively the effect of the concentration of magnesium stearate on the growth kinetics of the granulation and the overall development of the material wettability.