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Binder Selection in Pharmaceutical Granulation: Wetting, Spreading, Stickiness and Strength

Stefaan J. R. Simons, Department of Chemical Engineering, University College London, Torrington Place, London, WC1E 7JE, United Kingdom, Rob Ward, ERP Phase 2a Site Champion, Devlab, Merck Sharp & Dohme, Hertford Road, Hoddesdon, Herts, EN11 9BU, United Kingdom, Shaun Fitzpatrick, Development Laboratories, Merck Sharp & Dohme, Hertford Road, Hertfordshire EN11 9BU, Hoddesdon, United Kingdom, and Cristina Jimenez, Chemical Engineering, University College London, Torrington Place, London, WC1E 7JE, United Kingdom.

The choice of the correct binder and wetting agent in a granulation process can critically determine the performance and stability of the resultant granules. Clearly, the surface energy of the solid particles will have an impact on the ability of binder solution to spread across the surface of the particles. The same surface energy will also influence the strength of the adhesion of the solids to the dry binder. Both factors will determine how well the particles are bound into the granule a key determinant of solids segregation and content uniformity behaviour. In this paper, a micromanipulator technique has been used to differentiate between the interactions of different binders, namely, hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidone (PVP), with paracetamol crystals. Granule strength was also investigated, in terms of friability. Differences between the powder-wetting characteristics of these binder solutions were apparent in spite of the diversity of particle sizes and shapes employed. These differences are in line with those predicted on the basis of surface energy calculations and granule properties. The additional use of wetting agents, namely Sodium Lauryl Sulphate and Sodium Docusate, to improve the wetting behaviour and distribution of the binders on the particles will also be reported. The balance between binder adhesion (with the solid surfaces) and cohesion (for itself) in relation to granule growth is inferred from the interaction forces and the binder wetting behaviour. Comparisons will be made with other work being carried out at Merck, in regards to the properties of solid bridges of similar binders.