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AAPS PharmSciTech

, Volume 19, Issue 7, pp 2818–2827 | Cite as

Scale-Up and In-line Monitoring During Continuous Melt Extrusion of an Amorphous Solid Dispersion

  • Abbe Haser
  • Brian Haight
  • Andreas Berghaus
  • Augie Machado
  • Charlie Martin
  • Feng Zhang
Research Article Theme: Team Science and Education for Pharmaceuticals: the NIPTE Model
  • 30 Downloads
Part of the following topical collections:
  1. Theme: Team Science and Education for Pharmaceuticals: the NIPTE Model

Abstract

Chemical degradation of drug substances remains a major drawback of extrusion. Larger-scale extrusion equipment has advantages over smaller equipment due to deeper flight elements and added flexibility in terms of screw design, unit operations, and residence time. In a previous study, we extruded a meloxicam-copovidone amorphous solid dispersion (ASD) on a Nano-16 extruder and achieved 96.7% purity. The purpose of this study is to introduce a strategy for scaling the process to an extruder with dissimilar geometry and to investigate the impact on the purity of the ASD. The formulation previously optimized on the Nano-16, 10:90 meloxicam and copovidone, was used for scale-up. Our approach to scale-up to the ZSE-18, utilized specific mechanical energy input and degree of fill from the Nano-16. Vacuum was added to prevent hydrolysis of meloxicam. Downstream feeding and micronization of meloxicam were introduced to reduce the residence time. In-line monitoring of the solubilization of meloxicam was monitored with a UV probe positioned at the die. We were able to achieve the same purity of meloxicam with the Micro-18 as we achieved with Nano-16. When process conditions alone were not sufficient, meglumine was added to further stabilize meloxicam. In addition to the chemical stability advantage that meglumine provided, we also observed solubility enhancement which allowed for an increase in drug loading to 20% while maintaining 100% purity.

KEY WORDS

melt extrusion amorphous solid dispersion meloxicam chemical stability scale-up 

Notes

Acknowledgements

Some of this work was presented at the 2017 AAPS Annual Meeting and Exhibition, San Diego, CA. The authors would like to acknowledge Nada Kittikunakoin for her help in completing this work.

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Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Abbe Haser
    • 1
  • Brian Haight
    • 2
  • Andreas Berghaus
    • 3
  • Augie Machado
    • 2
  • Charlie Martin
    • 2
  • Feng Zhang
    • 1
  1. 1.Division of Pharmaceutics, College of PharmacyThe University of Texas at AustinAustinUSA
  2. 2.Leistritz ExtrusionSomervilleUSA
  3. 3.ColVisTecBerlinGermany

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