Continuous manufacturing of extended release tablets via powder mixing and direct compression

• Published in: International journal of pharmaceutics Vol. 495; no. 1; pp. 290 - 301
• Main Authors: Ervasti, Tuomas, Simonaho, Simo-Pekka, Ketolainen, Jarkko, Forsberg, Peter, Fransson, Magnus, Wikström, Håkan, Folestad, Staffan, Lakio, Satu, Tajarobi, Pirjo, Abrahmsén-Alami, Susanna
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 10-11-2015
• Subjects: Adaptive control; Continuous manufacturing; Continuous mixing; Delayed-Action Preparations - chemistry; Direct compression; Drug Industry - methods; Drug Liberation; Extended release; HPMC; Hypromellose Derivatives - chemistry; Ibuprofen - chemistry; Particle Size; Powders - chemistry; Solubility; Tablets - chemistry; Technology, Pharmaceutical - methods; Tensile Strength; Continuous manufacturing; Extended release; Direct compression; Adaptive control; Continuous mixing; HPMC
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2015.08.077

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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.