Hot-Melt extrusion coupled with pressurized carbon dioxide for enhanced processability of pharmaceutical polymers and drug delivery applications - An integrated review

Mashan Almutairi; Priyanka Srinivasan; Peilun Zhang; Fischer Austin; Arun Butreddy; Muteb Alharbi; Suresh Bandari; Eman A Ashour; Michael A Repka

doi:10.1016/j.ijpharm.2022.122291

Hot-Melt extrusion coupled with pressurized carbon dioxide for enhanced processability of pharmaceutical polymers and drug delivery applications - An integrated review

Int J Pharm. 2022 Dec 15:629:122291. doi: 10.1016/j.ijpharm.2022.122291. Epub 2022 Oct 14.

Authors

Mashan Almutairi¹, Priyanka Srinivasan², Peilun Zhang³, Fischer Austin⁴, Arun Butreddy⁵, Muteb Alharbi⁶, Suresh Bandari⁷, Eman A Ashour⁸, Michael A Repka⁹

Affiliations

¹ Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA; Department of Pharmaceutics, College of Pharmacy, University of Hail, Hail 81442, Saudi Arabia. Electronic address: msalmuta@go.olemiss.edu.
² Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA. Electronic address: psriniva@go.olemiss.edu.
³ Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA. Electronic address: pzhang3@go.olemiss.edu.
⁴ Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA.
⁵ Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA. Electronic address: abutredd@go.olemiss.
⁶ Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA. Electronic address: mjalharb@go.olemiss.edu.
⁷ Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA. Electronic address: sbandari@olemiss.edu.
⁸ Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA. Electronic address: eashour@olemiss.edu.
⁹ Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA; Pii Center for Pharmaceutical Technology, The University of Mississippi, University, MS 38677, USA. Electronic address: marepka@olemiss.edu.

PMID: 36252646
DOI: 10.1016/j.ijpharm.2022.122291

Abstract

Hot-melt extrusion (HME) technology is one of the primary approaches that has been implemented in recent years to overcome poor drug solubility/dissolution issues through the development of solid dispersion systems. Carbon dioxide (CO₂) either in supercritical (SupC) or subcritical (SubC) forms has been introduced to HME as a temporary plasticizer, reducing the operating temperature and eventually processing heat-sensitive molecules more efficiently. In this paper, a comprehensive review of CO₂-HME processes focused on pharmaceutical polymers and applications is presented. The steps and requirements for the setup of experimental devices are demonstrated, with a detailed influence of CO₂ characteristics on HME processes. The most relevant physical and chemical properties of pharmaceutical grade polymers subjected to the CO₂- HME process are described. The basic knowledge and main mechanisms of HME process parameters in conjunction with CO₂ concentration with regard to process feasibility and final product formation are discussed. HME coupled with CO₂ is extensively reviewed to provide a complete understanding of how to optimize the process parameters and conditions to reach optimized characteristics of final outcomes, as well as the sequential relationship between those outcomes (foaming → porosity → milling → tableting). Pharmaceutical applications of CO₂-based HME are presented in detailed case studies, including extrusion feasibility, solubility, dissolution rate enhancement, and gastroretentive or floating drug delivery. Finally, the current status of general CO₂-based techniques, as well as future perspectives and opportunities for promising applications through the integration of CO₂ with HME is presented.

Keywords: Foamy extrudates; Hot-melt extrusion; Polymers; Pressurized Carbon Dioxide; Processing parameters.

Publication types

Review

MeSH terms

Carbon Dioxide* / chemistry
Drug Compounding / methods
Hot Temperature
Polymers* / chemistry
Solubility
Tablets
Technology, Pharmaceutical / methods

Substances

Polymers
Carbon Dioxide
Tablets