(W1130-06-33) Reducing Degradation of a Ritonavir Amorphous Solid Dispersion by Managing Melt Temperature in a Twin Screw Extruder

Purpose: With thermally sensitive materials, processing on a twin-screw extruder (TSE) is sometimes a challenge. There are several techniques and concepts that can be applied to minimize the exposure of these materials to temperature. With consideration of factors including screw design, OD/ID ratios, throughput rate vs. screw rpm, and formulations, a system can be designed to minimize thermal exposure and create a robust process.

Methods: Various intermeshing TSE’s were used including ZSE 27 mm MAXX (co-rotating, 40:1 L/D, 14.3 cc/dia, 1.66 OD/ID), ZSE 27 mm HP (co-rotating, 40:1, 10.3 cc/dia, 1.55 OD/ID), and Micro 27 mm GG (counter-rotating, 28:1 L/D, 10.3 cc/dia, 1.55 OD/ID). Materials include pharmaceutical excipients and active ingredients including Copovidone and Ritonavir, and polymer systems including PLA and polypropylene. Processing conditions (rate, rpm, screw design, and temperatures) and formulations were varied to evaluate effects on melt temperature and degradation.

Results: With changes to screw design, OD/ID ratios, throughput rate vs. screw rpm, and formulations, melt temperatures were able to be decreased. Using polypropylene as a model polymer, a significant decrease of melt temperature was seen with modified melting section design, up to 40 °C in extreme cases of rate and rpm. By introducing a lubricant to a PLA formulation, the melt temperature was able to be reduced by 3 °C. Changing the OD/ID ratio from 1.55 to 1.66 with a similar PLA formulation, the melt temperature was able to be decreased 5 - 12 °C depending on the rate and rpm. After altering rpm to rate ratios on the co-rotating 27 mm HP with a Ritonavir formulation, melt temperature was reduced from 180 °C to 161 °C and degradation was decreased from 9.41% to 2.02%. Using these optimized processing conditions, the same formulation was tried on the counter-rotating Micro 27 mm. With further optimized screw design and processing conditions, melt temperature was decreased again to 157 °C and degradation was able to be decreased to 1.25%.

Conclusion: Overall, careful consideration of process design, with material properties in mind, is helpful to limit the thermal exposure of sensitive materials. Optimizing screw designs is helpful, however, comparing similar rates and rpm with different screw designs shows that processing conditions are in some cases more impactful to degradation than the screw design. A combination of the correct screw design, OD/ID and L/D ratios, and optimized processing conditions is the correct approach to designing an optimum process to reduce melt temperature and degradation.


Melting Zone Effect on Melt Temperature


PLA Melt Temperature Effects


Ritonavir Studies