title: Micro-mechanical properties of drying material bridges of pharmaceutical excipients.
abstract: This work is part of a larger research effort to elucidate the properties and morphology of pharmaceutical granules produced by wet-granulation. In this work, we measure forces exerted by the drying interparticle bridges. The bridges were formed from aqueous solutions of common pharmaceutical excipients both non-polymeric (lactose, mannitol) and polymeric (hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), polyvinylpyrrolidone (povidone) (PVP)). We also study the morphology, microstructure and crystalline structure of solidifying bridges. We find that the solidifying behavior and final properties of bridges differ dramatically, depending on the composition of the solution. Bridges containing only lactose or mannitol tend to expand upon solidification, pushing the ends of the bridge apart; in contrast, pure HPC, HPMC, or PVP bridges tend to contract. Bridges crystallized from solution of the pure non-polymeric excipients are polycrystalline, brittle, and have low strength; bridges from the polymeric excipients are amorphous, strong and tough. When the polymeric and non-polymeric excipients are used together, behavior closer to either one or the other extreme takes place. This depends on the relative amount of polymer in the bridge. It was also found that the different polymers impart different behavior on the bridge. The observed differences in solidification behavior have important implications for granule formation, drying and ultimate bridge and granule properties; these are discussed at some length in the paper.
authors.affiliation: Merck and Co. Inc., West Point, PA 19486, USA. Leon_Farber@Merck.com
authors.forename: Leon
authors.initials: L
authors.lastname: Farber
authors.forename: Gabriel I
authors.initials: GI
authors.lastname: Tardos
authors.forename: James N
authors.initials: JN
authors.lastname: Michaels
mesh_terms: D003460:Crystallization; D005079:Excipients / Q000737:chemistry*; D008422:Materials Testing / Q000295:instrumentation / Q000379:methods*; D033362:Powder Diffraction; D012996:Solutions; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D013816:Thermodynamics
chemical_list: D005079:Excipients; D012996:Solutions