Solid Dispersions by Hot-Melt Extrusion - Pharmaceutical Technology

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Solid Dispersions by Hot-Melt Extrusion
The advantages and disadvantages of hot-melt extrusion in solid dispersion formulations


Pharmaceutical Technology Europe
Volume 24, Issue 9

Process understanding and process design

To develop the melt extrusion process in an appropriate manner it is important to have tools to characterize and analyze the process. It is clear that only an optimized formulation together with an optimized process set-up will yield the best product.

Besides the parameters such as screw speed and feed rate, which can be adjusted during the extrusion process, screw configuration is a major parameter. Screw design is not often optimized although it plays a major role in determining product quality. Screw configuration basically determines the shear stress. It also strongly influences the residence time distribution. BASF's second edition of the HME compendium provides more information on the design of screws in co-rotating twin screw extruders. Here, the functionality of different screw segments is explained in detail.

The new HME compendium also shows how to determine residence time distribution and how to read it. It provides a guide for process analysis and for developing better process understanding.

BASF has also developed a process parameter chart that enables the whole extrusion process with all its influencing variables to be included. The advantages of the new process parameter chart are:

  • It displays technical aspects.
  • It also displays the economic effects of changes made in process design.
  • It is scale-independent and can be used in scale-up procedures.


Figure 8: Process parameter chart.
The proposed process parameter chart is shown in Figure 8. It is a XY-diagram, displaying the volume-specific feed load (VSFL) versus the extrusion temperature (mean barrel temperature).

Throughput triggers cost. The throughput in an extruder can be either torque-limited or volume-limited. In Figure 8, one curve represents the determined maximum achievable VSFL values at the limit of the extruder. The vertical line indicates the process boundary. Only the position on the temperature axis is relevant for reading the line; the line height does not matter. Each VSFL value to the left of the line is limited by the maximum torque of the extruder (configuration), while each VSFL value to the right of the line is limited by maximum intake (volume). The vertical dotted line on the right indicates the process boundary given by the maximum allowable temperature, which can be determined by the degradation points of either the active substance or any non-active ingredient in the processed formulation. The design space can be filled with contour lines of extrusion system parameters such as mean residence time for better process analysis.

More information on the process parameter chart and its use can be found in BASF's new HME compendium (see below).

References

1. S. Janssens and G. Van den Mooter, JPP 2009, 61: 1571–1586, DOI 10.1211/jpp/61.12.0001

2. H. H. Görtz et al., EP 0240904 B1

3. C. Leuner and J. Dressman, Eur. J. Pharm. Biopharm. 50, 47-60 (2000).




Download for free the new edition of the hot-melt extrusion compendium at: http://www.innovate-excipients.basf.com/


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