TY - JOUR
T1 - Optimization of screw design for continuous wet granulation
T2 - A case study of metoprolol succinate ER tablets
AU - Zidan, Ahmed
AU - Kotamarthy, Lalith
AU - Ramachandran, Rohit
AU - Ashraf, Muhammad
AU - O'Connor, Thomas
N1 - Funding Information:
This project was supported by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and FDA.
Publisher Copyright:
© 2022
PY - 2022/7/25
Y1 - 2022/7/25
N2 - 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.
AB - 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.
KW - Continuous manufacturing
KW - Design space
KW - Extended-release tablets
KW - Processing
KW - Screw design
KW - Twin screw granulation
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U2 - 10.1016/j.ijpharm.2022.121964
DO - 10.1016/j.ijpharm.2022.121964
M3 - Article
C2 - 35764264
AN - SCOPUS:85133289467
SN - 0378-5173
VL - 623
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
M1 - 121964
ER -