title: Influence of metronidazole particle properties on granules prepared in a high-shear mixer-granulator.
abstract: Metronidazole is a good example of high-dose drug substance with poor granulating and tableting properties. Tablets are generally produced by liquid granulation; however, the technological process failure is quite frequent. In order to verify how the metronidazole particle characteristics can influence granule properties, three metronidazole batches differing for crystal habit, mean particle size, BET surface area and wettability were selected, primarily designed according to their different elongation ratio: needle-shaped, stick-shaped, and isodimensional. In the presence of lactose monohydrate and pregelatinized maize starch, respectively as diluent and binder, they were included in a formula for wet granulation in a high-shear mixer-granulator. In order to render the process comparable as far as possible, all parameters and experimental conditions were maintained constant. Four granule batches were obtained: granules from placebo (G-placebo), granules from needle-shaped crystals (G-needle-shaped), granules from stick-shaped crystals (G-stick-shaped), and granules from isodimensional crystals (G-isodimensional). Different granule properties were considered, in particular concerning porosity, friability, loss on drying (LOD), and flowability. In order to study their tabletability and compressibility, the different granules obtained were then compressed in a rotary press. The best tabletability was obtained with the isodimensional batch, while the poorest was exhibited by the stick-shaped one. Differences in tabletability are in good accordance with compressibility results: to a better tabletability corresponds an important granule ability to undergo a volume reduction as a result of an applied pressure. In particular, it was proposed that the greatest compressibility of the G-isodimensional must be related to the greatest granule porosity percentage.
authors: Dipartimento di Scienze Chimiche, Laboratorio di Tecnica Farmaceutica, Via S. Agostino, Camerino, Italy. piera.dimartino@unicam.it
authors: Piera
authors: P
authors: Di Martino
authors: Roberta
authors: R
authors: Censi
authors: Ledjan
authors: L
authors: Malaj
authors: Sante
authors: S
authors: Martelli
authors: Etienne
authors: E
authors: Joiris
authors: Christine
authors: C
authors: Barthélémy
mesh_terms: D000085:Acetates / Q000737:chemistry; D000890:Anti-Infective Agents / Q000737:chemistry; D000440:Butanols / Q000737:chemistry; D002482:Cellulose / Q000737:chemistry; D019245:Compressive Strength; D003460:Crystallization; D003890:Desiccation / Q000379:methods; D004339:Drug Compounding / Q000295:instrumentation* / Q000379:methods; D004345:Drug Industry / Q000379:methods; D006245:Hardness Tests / Q000379:methods; D007785:Lactose / Q000737:chemistry; D008795:Metronidazole / Q000737:chemistry*; D010316:Particle Size; D016062:Porosity; D011208:Powders; D012997:Solvents / Q000737:chemistry; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000295:instrumentation* / Q000379:methods; D014867:Water / Q000737:chemistry; D017155:Wettability; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D000085:Acetates; D000890:Anti-Infective Agents; D000440:Butanols; D011208:Powders; D012997:Solvents; D013607:Tablets; D014867:Water; D008795:Metronidazole; C007650:ethyl acetate; D002482:Cellulose; D007785:Lactose; C109691:microcrystalline cellulose