Hot melt extrusion: An emerging manufacturing method for slow and sustained protein delivery

Abstract

With the rapid development of the biopharmaceutical industry, an increasing number of new therapeutic protein products (TPPs) have been approved by the FDA and many others are under pre‐clinical and clinical evaluation. A major limitation of biopharmaceuticals is their limited half‐life when administered systemically. A one‐time, implantable, sustained protein delivery device would be advantageous in order to improve the quality of life of patients. Hot melt extrusion (HME) is a mature technology that has been extensively used for a broad spectrum of applications in the polymer and pharmaceutical industry and has achieved success as evidenced by a variety of FDA‐approved commercial products. These commercial products are mostly for sustained delivery of small molecule therapeutics, leaving a significant gap for HME formulation of therapeutic proteins. With the increasing need of sustained TPP delivery, HME shows promise as a downstream processing method due to its high efficiency and economic value. Several challenges remain for the application of HME in protein delivery. Progress of HME for protein delivery, challenges encountered, and potential solutions will be detailed in this review article. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Biology‐Inspired Nanomaterials > Protein and Virus‐Based Structures

Impact of process stress on protein stability in highly-loaded solid protein/PEG formulations from small-scale melt extrusion

“…In this case, the protein particles act as fillers resulting in a reduced amount of energy required for the viscous dissipation during melt extrusion processing ( Lyons et al, 2006 ). Polymers can ensure the thermodynamically stable folded structure of a protein during the melt extrusion process due to the immobilization of protein molecules in the polymeric matrix, which is critical for a successful protein formulation development ( Ghalanbor et al, 2010 ; Lee et al, 2006 ; Zheng and Pokorski, 2021 ). Furthermore, by melt extrusions processing a high fraction of protein can be embed into a polymeric matrix resulting in high-drug loads (i.e., >40% protein) compared to other formulation techniques.…”

Biocomposite Thermoplastic Polyurethanes Containing Evolved Bacterial Spores as Living Fillers to Facilitate Polymer Disintegration

“…HME, used in this work, is an established technology for industrial polymer manufacturing and more than half of all plastic products are fabricated by HME 40,69 . The scale-up and scale-down of TSE-based HME is widely studied 70 , and the throughput of BC TPU fabrication (15 g/h) by the benchtop TSE ( Supplementary Fig.…”

New IMB16-4 Hot-Melt Extrusion Preparation Improved Oral Bioavailability and Enhanced Anti-Cholestatic Effect on Rats

“…[19][20][21] As an innovative high-technology in pharmaceutical industry, hot-melt extrusion (HME) technique was widely recommended for improving the solubility and oral bioavailability of insoluble drugs. 22,23 In this study, a HME preparation was first applied to explore the effect of IMB16-4 on α-naphthy lisothiocyanate (ANIT) induced cholestasis in rats. Our data confirmed that the HME preparation significantly improved the oral bioavailability of pure IMB16-4.…”