Optimization of screw design for continuous wet granulation: A case study of metoprolol succinate ER tablets

Ahmed Zidan, Lalith Kotamarthy, Rohit Ramachandran, Muhammad Ashraf, Thomas O'Connor

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


This study aimed at understanding the effect of screw design on the critical characteristics of granules and tablets of an extended-release (ER) formulation for twin screw granulation process. The screw design parameters assessed included number of kneading elements (KEs) per kneading zone, distance separating kneading zones, staggering angle (SA) of kneading elements and number of sizing elements (SEs). These input variables were varied using a design of experiment (DoE) approach to manufacture granules. Particle size distribution (PSD), flow and bulk properties of the granules, breaking strength and dissolution of tablets manufactured using these granules were characterized. The results of least square fitting showed that KEs, SA, and SEs of the screws significantly (p -values < 0.05) affected the PSD, cohesion, compressibility (CPS), conditioned bulk density (CBD) and permeability of the granules. The KEs and SEs significantly (p -value < 0.05) affected the dissolution, which was attributed to their effects on CPS and CBD of the granules. The distance between kneading zones had no significant effect on granules and tablet characteristics. These results may be used to further study the interaction of the identified critical screw design parameters with other processing parameters for continuous manufacturing of this ER matrix-based tablet formulation.

Original languageEnglish (US)
Article number121964
JournalInternational Journal of Pharmaceutics
StatePublished - Jul 25 2022
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science


  • Continuous manufacturing
  • Design space
  • Extended-release tablets
  • Processing
  • Screw design
  • Twin screw granulation


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