title: Effects of high-shear granulation on granulate homogeneity.
abstract: This study considers the effects of particle size of the powder constituents, and of impeller speed on the homogeneity of drug distribution on granulations produced in high-speed mixers. When a micronized low-dose steroid hormone was granulated together with unmicronized lactose in a Vactron 75 high-shear granulator at 250 rpm, strong inhomogeneities of the drug distribution arose. The coarse particle size fractions of the granules were found to be superpotent up to 150% of the mean drug content, whereas the fine size fraction showed a corresponding subpotency of 50%. Both particle size and impeller speed attributed to this phenomenon. At an impeller speed of 75 rpm, a significantly better drug distribution was obtained. Results show that the inhomogeneities found are mainly a consequence of the balance between the impact pressure as exerted by the impeller on the one hand and the shear resistance of the nuclei on the other hand. At a speed of 250 rpm, the tensile strength of 3 x 10(3) N/m2 of the initially formed nuclei is too weak to resist an impact pressure of 30 x 10(3) N/m2. For that reason, particle rearrangement takes place, which results in inhomogeneity. Because an impeller speed of 75 rpm is equal to an impact pressure of 2.6 x 10(3) N/m2, significantly less demixing occurs. Similar results can be obtained when the particle size of all constituents is reduced, which increases the tensile strength of the nuclei.
authors.affiliation: Department of Pharmaceutics, n.v. Organon, Oss, The Netherlands. h.vromans@organon.oss.akzonobel.nl
authors.forename: H
authors.initials: H
authors.lastname: Vromans
authors.forename: H G
authors.initials: HG
authors.lastname: Poels-Janssen
authors.forename: H
authors.initials: H
authors.lastname: Egermann
mesh_terms: D000465:Algorithms; D004339:Drug Compounding / Q000295:instrumentation* / Q000379:methods; D005079:Excipients; D006728:Hormones / Q000737:chemistry; D010316:Particle Size; D011208:Powders; D013256:Steroids / Q000737:chemistry
chemical_list: D005079:Excipients; D006728:Hormones; D011208:Powders; D013256:Steroids