Design and scale-up of amorphous drug nanoparticles production via a one-step anhydrous continuous process

Esther Jacobs, Kaije Qian, Valerie L. Pietsch, Margarethe Richter, David S. Jones, Gavin P. Andrews, Yiwei Tian*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)
53 Downloads (Pure)

Abstract

Polymeric nanoparticle drug delivery systems are increasingly viewed as crucial building blocks for efficacious treatments of disease conditions. However, production methods at commercially practical scales pose a significant challenge for successfully translating such technology. This paper describes a novel, anhydrous, twin-screw extrusion (TSE) platform-based technology to overcome the issues associated with developing and scale-up production of nanoparticulate drug delivery systems. With polyol as the process medium, the proposed TSE platform enables the encapsulation of the drug and reduction of particle size in a one-step process without the requirement for organic solvents or water. pH-responsive nanoparticle drug delivery of two nonsteroidal anti-inflammatory drugs, naproxen, and celecoxib, was successfully produced using the TSE process. Remarkably, these resulted in nanoparticles with sizes ranging from 80 to 240 nm, up to 98 % drug encapsulation efficiency, and maximum production throughput of 400 g/hour. pH-responsive drug release for both naproxen and celecoxib was also achieved: immediate drug release with enhanced solubility was obtained for naproxen-Eudragit®E nanoparticles (6 times higher) at pH 1.2 and celecoxib-HPMCAS nanoparticles (15 times higher) at pH 6.8, whilst sustained drug release was achieved for naproxen-Eudragit®E nanoparticles at pH 6.8 and celecoxib-HPMCAS nanoparticles at pH 1.2. We expect this platform technology to streamline the development and scale-up production of various polymeric nanoparticle drug delivery systems.

Original languageEnglish
Article number122304
Number of pages14
JournalInternational Journal of Pharmaceutics
Volume628
Early online date21 Oct 2022
DOIs
Publication statusPublished - 25 Nov 2022

Keywords

  • Green process
  • High drug loading
  • Nanosized amorphous solid dispersion
  • Polymeric nanoparticles
  • Scale-up
  • Thermodynamic modelling
  • Twin-screw extrusion

ASJC Scopus subject areas

  • Pharmaceutical Science

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