Twin-screw granulation and high-shear granulation: The influence of mannitol grade on granule and tablet properties

Abstract

Granule structure has a key influence on tablet critical quality attributes. The ability to control this structure through excipient choice is an important part of formulation development. Mannitol is a popular diluent and the choice of input grade has been shown to impact granule properties. Allopurinol formulations containing two grades of mannitol (Pearlitol 160C and 200SD) were prepared by wet-granulation (twin-screw and high-shear) at different liquid/solid ratios (0.3 and 0.6 g/g). The particle and bulk properties were characterised by a range of techniques and linked to flow performance and tablet tensile strength during compression on a rotary tablet press. During granulation, 200SD underwent a polymorphic transition from a mixture of α and β to predominantly β. This transition was accompanied by a morphology change. Mannitol needles were formed, giving more porous granules with a higher specific surface area, which led to poorer flow properties but higher tablet tensile strength. This study concludes that understanding the effect of mannitol grade is a crucial part of formulation selection.

Keywords: Continuous; Formulation development; Granule properties; Mannitol; Polymorphism; Twin-screw wet granulation.