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Continuous manufacture of hydroxychloroquine sulfate drug products via hot melt extrusion technology to meet increased demand during a global pandemic: From bench to pilot scale.
de Margerie, Victoire; McConville, Christopher; Dadou, Suha M; Li, Shu; Boulet, Pascal; Aranda, Lionel; Walker, Andrew; Mohylyuk, Valentyn; Jones, David S; Murray, Brian; Andrews, Gavin P.
  • de Margerie V; Rondol Industrie, 2 Allée André Guinier, 54000 Nancy, France.
  • McConville C; School of Pharmacy, Institute of Clinical Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston B15 2TT, United Kingdom.
  • Dadou SM; Pharmaceutical Engineering Group, School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, United Kingdom; China Medical University - Queen's University Belfast joint College (CQC), No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province, PR China.
  • Li S; Pharmaceutical Engineering Group, School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, United Kingdom; China Medical University - Queen's University Belfast joint College (CQC), No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province, PR China.
  • Boulet P; Institut Jean Lamour, UMR 7198 CNRS-Université de Lorraine, 2 Allée André Guinier, 54000 Nancy, France.
  • Aranda L; Institut Jean Lamour, UMR 7198 CNRS-Université de Lorraine, 2 Allée André Guinier, 54000 Nancy, France.
  • Walker A; Rondol Industrie, 2 Allée André Guinier, 54000 Nancy, France.
  • Mohylyuk V; Pharmaceutical Engineering Group, School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, United Kingdom; China Medical University - Queen's University Belfast joint College (CQC), No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province, PR China.
  • Jones DS; Pharmaceutical Engineering Group, School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, United Kingdom.
  • Murray B; Rondol Industrie, 2 Allée André Guinier, 54000 Nancy, France.
  • Andrews GP; Pharmaceutical Engineering Group, School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, United Kingdom; China Medical University - Queen's University Belfast joint College (CQC), No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province, PR China. Electronic address: g.andrews
Int J Pharm ; 605: 120818, 2021 Aug 10.
Article in English | MEDLINE | ID: covidwho-1457706
ABSTRACT
During pandemics and global crises, drug shortages become critical as a result of increased demand, shortages in personnel and lockdown restrictions that disrupt the supply chain. The pharmaceutical industry is therefore moving towards continuous manufacturing instead of conventional batch manufacturing involving numerous steps, that normally occur at different sites. In order to validate the use of large-scale industrial processes, feasibility studies need to be performed using small-scale laboratory equipment. To that end, the scale-up of a continuous process and its effect on the critical quality attributes (CQAs) of the end product were investigated in this work. Hydroxychloroquine Sulphate (HCQS) was used as the model drug, Soluplus® as a model polymeric carrier and both horizontal and vertical twin screw extruders used to undertake this hot melt extrusion (HME) study. Seven formulations were processed using a small-scale horizontal extruder and a pilot-scale vertical extruder at various drug loadings, temperature profiles and screw speeds. When utilising a horizontal extruder, formulations with the highest drug load and processed at the lowest screw speed and temperature had the highest crystallinity with higher drug release rates. Upon scale-up to a vertical extruder, the crystallinity of the HCQS was significantly reduced, with less variation in both crystallinity and release profile across the different extrudates. This study demonstrates improved robustness with the pilot-scale vertical extruder compared to lab-scale horizontal extruder. The reduced variation with the vertical extruder will allow for short increases in production rate, with minimum impact on the CQAs of the final product enabling high-performance continuous manufacturing with minimum waste of raw materials. Finally, this research provides valuable information for the pharmaceutical industry in accessing continuous technologies for the manufacture of pharmaceutical products, allowing for efficient utilisation of resources upon scale-up and mass production during global pandemics and drug shortages.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pharmaceutical Preparations / Hot Melt Extrusion Technology Type of study: Prognostic study Language: English Journal: Int J Pharm Year: 2021 Document Type: Article Affiliation country: J.ijpharm.2021.120818

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pharmaceutical Preparations / Hot Melt Extrusion Technology Type of study: Prognostic study Language: English Journal: Int J Pharm Year: 2021 Document Type: Article Affiliation country: J.ijpharm.2021.120818