title: The role of the kneading paddle and the effects of screw revolution speed and water content on the preparation of solid dispersions using a twin-screw extruder.
abstract: The twin-screw hot-melt extrusion process is useful for preparing solid dispersions which can improve the dissolution and absorption of drugs. The kneading paddle elements of the screws play an important role in changing the crystallinity and dissolution properties of a solid dispersion of kneaded nifedipine-hydroxypropylmethylcellulose phthalate (NP-HPMCP). After operating the machine, a small amount of kneaded material adhering to the screws was collected and its physicochemical properties examined. Samples from the kneading paddle with a twist angle of 60 degrees were transparent and exhibited super-saturation on dissolution testing. When the kneading paddle elements were detached from the screws and only the feed screw elements were operated, the physicochemical properties of the extruded material were significantly influenced by the operating conditions of the machine e.g. revolution rate of screws, and the amount of water added to the feed materials. Slow revolution of the screws and the addition of a suitable amount of water to the mixture increased the rate of drug dissolution, although no super-saturation occurred. As the kneading paddle elements can retain the mixture in the machine for a longer period under intense shear, desired solid dispersions can be prepared routinely irrespective of the operating conditions. Moreover, a capillary rheometer can be useful to predetermine the amount of water added and the temperature for the preparation of solid dispersions using a twin-screw extruder.
authors.affiliation: Pharmaceutics Research Laboratory, Nippon Shinyaku Co., Ltd., 14, Nishinosyou-Monguti-cho, Kisshoin, Minami-ku, Kyoto 601-8550, Japan. k.nakamichi@po.nippon-shinyaku.co.jp
authors.forename: Kouichi
authors.initials: K
authors.lastname: Nakamichi
authors.forename: Tomio
authors.initials: T
authors.lastname: Nakano
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yasuura
authors.forename: Shogo
authors.initials: S
authors.lastname: Izumi
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kawashima
mesh_terms: D002121:Calcium Channel Blockers; D002626:Chemistry, Pharmaceutical; D004867:Equipment Design; D008747:Methylcellulose / Q000031:analogs & derivatives; D009543:Nifedipine; D013678:Technology, Pharmaceutical / Q000295:instrumentation*
chemical_list: D002121:Calcium Channel Blockers; D008747:Methylcellulose; C053309:hydroxypropyl methylcellulose phthalate; D009543:Nifedipine