title: Continuous manufacturing of extended release tablets via powder mixing and direct compression.
abstract: The aim of the current work was to explore continuous dry powder mixing and direct compression for manufacturing of extended release (ER) matrix tablets. The study was span out with a challenging formulation design comprising ibuprofen compositions with varying particle size and a relatively low amount of the matrix former hydroxypropyl methylcellulose (HPMC). Standard grade HPMC (CR) was compared to a recently developed direct compressible grade (DC2). The work demonstrate that ER tablets with desired quality attributes could be manufactured via integrated continuous mixing and direct compression. The most robust tablet quality (weight, assay, tensile strength) was obtained using high mixer speed and large particle size ibuprofen and HPMC DC2 due to good powder flow. At low mixer speed it was more difficult to achieve high quality low dose tablets. Notably, with HPMC DC2 the processing conditions had a significant effect on drug release. Longer processing time and/or faster mixer speed was needed to achieve robust release with compositions containing DC2 compared with those containing CR. This work confirms the importance of balancing process parameters and material properties to find consistent product quality. Also, adaptive control is proven a pivotal means for control of continuous manufacturing systems.
authors: University of Eastern Finland, Faculty of Health Sciences, School of Pharmacy, Kuopio, Finland.
authors: Tuomas
authors: T
authors: Ervasti
authors: University of Eastern Finland, Faculty of Health Sciences, School of Pharmacy, Kuopio, Finland.
authors: Simo-Pekka
authors: SP
authors: Simonaho
authors: University of Eastern Finland, Faculty of Health Sciences, School of Pharmacy, Kuopio, Finland.
authors: Jarkko
authors: J
authors: Ketolainen
authors: AstraZeneca R&D, Mölndal, Sweden.
authors: Peter
authors: P
authors: Forsberg
authors: AstraZeneca R&D, Mölndal, Sweden.
authors: Magnus
authors: M
authors: Fransson
authors: AstraZeneca R&D, Mölndal, Sweden.
authors: Håkan
authors: H
authors: Wikström
authors: AstraZeneca R&D, Mölndal, Sweden.
authors: Staffan
authors: S
authors: Folestad
authors: AstraZeneca R&D, Mölndal, Sweden.
authors: Satu
authors: S
authors: Lakio
authors: AstraZeneca R&D, Mölndal, Sweden.
authors: Pirjo
authors: P
authors: Tajarobi
authors: AstraZeneca R&D, Mölndal, Sweden. Electronic address: susanna.abrahmsen-alami@astrazeneca.com.
authors: Susanna
authors: S
authors: Abrahmsén-Alami
mesh_terms: D003692:Delayed-Action Preparations / Q000737:chemistry*; D004345:Drug Industry / Q000379:methods*; D065546:Drug Liberation; D065347:Hypromellose Derivatives / Q000737:chemistry*; D007052:Ibuprofen / Q000737:chemistry*; D010316:Particle Size; D011208:Powders / Q000737:chemistry; D012995:Solubility; D013607:Tablets / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods*; D013718:Tensile Strength
chemical_list: D003692:Delayed-Action Preparations; D011208:Powders; D013607:Tablets; D065347:Hypromellose Derivatives; C584694:hypromellose 2208 (100 MPA.S); D007052:Ibuprofen
keywords: Adaptive control; Continuous manufacturing; Continuous mixing; Direct compression; Extended release; HPMC