Control of residence time of pharmaceutical powder in a continuous mixer with impeller and scraper

• Published in: International journal of pharmaceutics Vol. 586; p. 119520
• Main Authors: Tomita, Yosuke, Nagato, Takuya, Takeuchi, Yoshiko, Takeuchi, Hirofumi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30-08-2020
• Subjects: Acetaminophen - administration & dosage; Acetaminophen - chemistry; Chemistry, Pharmaceutical - methods; Continuous manufacturing; Drug Compounding - methods; Excipients - chemistry; Pharmaceutical granulation; Powder mixer; Powders; Residence time distribution; Technology, Pharmaceutical - methods; Time Factors; Residence time distribution; Continuous manufacturing; Pharmaceutical granulation; Powder mixer
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2020.119520

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The control of residence time in a powder mixing process was investigated toward the development of a continuous pharmaceutical manufacturing system. A powder mixer equipped with an impeller and a scraper, which was designed for a continuous granulation machine, was used. The mixing homogeneity and dynamic behavior of the powder in the mixer were investigated by using a tracer, acetaminophen, in impulse- and step-response experiments. The homogeneity of the mixture was guaranteed by the high rotation speed of the impeller, independent of the speed of the scraper. The mean residence time of the powder was controlled by changing the scraper speed. The hold-up weight in the mixer was also changed by the scraper speed. In the measurement of the hold-up weight, the scraper speed also affected the powder filling density. These results confirmed that the scraper equipped in the mixer transported powder towards the exit of the mixer, and that both the scraper’s rotation speed and its shape are key parameters for flexibly controlling the residence time of powder in the mixer. These experimental results can provide useful information for adjusting the residence time in order to optimize conditions for the corresponding continuous granulation system.