Continuous direct tablet compression: effects of impeller rotation rate, total feed rate and drug content on the tablet properties and drug release

Abstract

Context: Continuous processing is becoming popular in the pharmaceutical industry for its cost and quality advantages.

Objective: This study evaluated the mechanical properties, uniformity of dosage units and drug release from the tablets prepared by continuous direct compression process.

Materials and methods: The tablet formulations consisted of acetaminophen (3–30% (w/w)) pre-blended with 0.25% (w/w) colloidal silicon dioxide, microcrystalline cellulose (69–96% (w/w)) and magnesium stearate (1% (w/w)). The continuous tableting line consisted of three loss-in-weight feeders and a convective continuous mixer and a rotary tablet press. The process continued for 8 min and steady state was reached within 5 min. The effects of acetaminophen content, impeller rotation rate (39–254 rpm) and total feed rate (15 and 20 kg/h) on tablet properties were examined.

Results and discussion: All the tablets complied with the friability requirements of European Pharmacopoeia and rapidly released acetaminophen. However, the relative standard deviation of acetaminophen content (10% (w/w)) increased with an increase in impeller rotation rate at a constant total feed rate (20 kg/h). A compression force of 12 kN tended to result in greater tablet hardness and subsequently a slower initial acetaminophen release from tablets when compared with those made with the compression force of about 8 kN.

Conclusions: In conclusion, tablets could be successfully prepared by a continuous direct compression process and process conditions affected to some extent tablet properties.

Keywords::

• Continuous direct tablet compression
• continuous powder mixing
• acetaminophen
• tablet mechanical properties
• crushing strength
• content uniformity
• dissolution

Acknowledgements

We would like to thank Aditya U Vanarase, PhD (Chemical and Biochemical Engineering, Rutgers The State University of New Jersey), Maunu Toiviainen, M. Sc. (Tech) and Pekka Teppola, PhD (Tech.) (VTT Technical Research Centre of Finland, Kuopio) and Aleksi Takala M. Sc. (Pharm.) for the cooperation during the work.

Declaration of interest

This research was funded by Finnish Funding Agency of Technology and Innovation (COCO consortium).