Multiple batch manufacturing of theophylline pellets using the wet-extrusion/spheronization process with κ-carrageenan as pelletisation aid

Abstract

κ-Carrageenan has been suggested as a pelletisation aid for wet-extrusion/spheronization processes for several years. Until now there have been no systematic investigations regarding process development and stability for long-term production. The aim of this study was to develop a high drug-loaded pellet formulation with κ-carrageenan, so that a robust process cycle occurred over the course of several hours. Binary mixtures of κ-carrageenan and theophylline monohydrate were used and the drug content was varied from 90 to 95%. A twin-screw extruder was used; the power consumption and feed rates were recorded. The pellets were characterized by aspect ratio, diameter, 10% interval, tensile strength and dissolution behavior. The process ran on two occasions for 4.5 h each time. During the extrusion process neither the power consumption nor the feed rates differed significantly, so there was no need to stop the process or change the extrusion parameters. Regarding the spheronization, a cleaning of the spheroniser friction plate was necessary every five batches due to packing of the material on this plate. Overall the resulting pellets showed reproducible and adequate qualities regarding all investigated properties. In conclusion a robust pelletisation process over several hours could be verified. It was possible to produce 42 kg of pellets with adequate properties, without any problems during the process.

Keywords::

• Robustness
• formulation development
• process development

Acknowledgments

We gratefully acknowledge BASF SE (Ludwigshafen, Germany) for donating materials, and the assistance of Elizabeth Ely (EIES, Lafayette IN, USA) in preparing the manuscript.

Declaration of interest

The authors declare no conflicts of interest.

Appendix

The specific mechanical energy (SME) is defined as

7

with E as energy and m as mass. The power (P) for a motor is given by (Eq. 8)

8

with τ as torque, f as frequency of rotation and t as time, which leads to:

9

Integrating both sides assuming a constant torque and frequency are constant with respect to time:

10

The combination of equation 7 and 10 gives

11

and if the mass flow rate is constant, then

12

then

13