title: Tabletting of pellet-matrix systems: ability of parameters from dynamic and kinetic models to elucidate the densification of matrix formers and of pellets.
abstract: Two different types of pellets, i.e. drug-free sugar spheres, and pellets, spray-layered with crystalline theophylline and coated with Eudragit RS/RL, were tabletted each in combination with matrix-forming powder mixtures of Avicel PH200 and PEG 4000. The die fills from pellets and powder mixtures were regarded as two-compartment systems with a volume fraction of the pellets being limited to 0.52 corresponding to a cubic lattice, and the maximum degrees of densifications were adjusted related to the matrix. To data measured during single compression cycles on an instrumented eccentric tabletting machine and transformed appropriately, the Kawakita equation, the Heckel function, and a modified Weibull function were fitted, and the total work of compression was calculated. The Kawakita model fitted well systems with both types of pellets. Its parameters reflected the additional densification of the theophylline pellets separately from that of the matrix formers. The Heckel function could only be applied to systems containing non-porous sugar spheres, since the theophylline pellets underwent considerable densification and deformation. Only, when the Heckel porosity function was related to the volume fraction of the matrix, excluding the sugar spheres, the approximately linear regions for mixtures with increasing volume proportions of sugar spheres occured in comparable regions of densification. Parameters of the modified Weibull function demonstrated an increasing resistance against densification with increasing amounts of pellets. The total work of compression increased steeply with increasing volume fractions for pellets from 0.42 to 0.46 indicating, that the resistance against densification already rose when the pellets were still isolated. In conclusion, the combination of dynamic and kinetic models provides a comprehensible insight into the process of tabletting powder mixtures with pellets. Particularly, the Kawakita model was a suitable tool to differentiate the actual changes in porosity during compression from the compressibility of such complex systems.
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, University of Hamburg, Bundesstrasse 45, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kühl
authors.forename: Jobst B
authors.initials: JB
authors.lastname: Mielck
mesh_terms: D019245:Compressive Strength; D004343:Drug Implants / Q000737:chemistry* / Q000493:pharmacokinetics; D007700:Kinetics; D008863:Microspheres; D008956:Models, Chemical; D016062:Porosity; D013607:Tablets / Q000737:chemistry* / Q000493:pharmacokinetics; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D004343:Drug Implants; D013607:Tablets