title: Roll compaction of mannitol: compactability study of crystalline and spray-dried grades.
abstract: Purpose of this project was to investigate the roll compaction behavior of various mannitol grades. Therefore, five spray-dried grades as well as unprocessed β-d-mannitol were roll compacted with different compaction forces. The resulting granules were characterized with regard to their particle size distribution, flow properties, and BET surface area and compressed to tablets. Granules of unprocessed mannitol, even when applying high compaction forces during dry granulation, were characterized by a high amount of fines (about 21%), a small surface area (0.83 m(2)/g), and solely fair flowability (ffc=7.2). Tablets revealed either high friability or insufficient disintegration behavior. However, the use of spray-dried mannitol led to better results. Granules showed improved flow properties and a reduced amount of fines. Robust tablets with low friability were produced. Within the various spray-dried grades huge differences concerning the compactability were observed. Large BET surface areas of the granules resulted in advanced tensile strengths of the tablets, but acceptable disintegration behavior was maintained. These findings are relevant for the development of mannitol based drug formulations, in particular (oro)dispersible tablets containing a low dose or poor flowing active pharmaceutical ingredient, where direct compression is inappropriate and a granulation process prior to tableting is mandatory.
authors.affiliation: Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine University of Düsseldorf, 40225 Düsseldorf, Germany. carl.wagner@hhu.de
authors.forename: Carl Moritz
authors.initials: CM
authors.lastname: Wagner
authors.forename: Miriam
authors.initials: M
authors.lastname: Pein
authors.forename: Jörg
authors.initials: J
authors.lastname: Breitkreutz
mesh_terms: D003890:Desiccation / Q000379:methods; D004339:Drug Compounding / Q000379:methods*; D005079:Excipients / Q000737:chemistry*; D008353:Mannitol / Q000737:chemistry*; D016062:Porosity; D013499:Surface Properties; D013607:Tablets; D013718:Tensile Strength
chemical_list: D005079:Excipients; D013607:Tablets; D008353:Mannitol
keywords: Compactability; Dry granulation; Mannitol; Roll compaction; Work-hardening