Article Dans Une Revue International Journal of Pharmaceutics Année : 2021

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

Résumé

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 technologies that involve numerous steps usually occurring at different sites. In order to validate large-scale commercial manufacturing, feasibility studies need to be performed first, using small-scale laboratory equipment. To that end, the scale-up of a continuous process and its effect on the quality 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 Rondol machines as the extruders. Seven formulations were processed using a small scale horizontal extruder and a large-scale vertical extruder at various temperatures and speeds. On the horizontal extruder, low drug loading and high barrel temperatures were the main factors affecting the solid-state of HCQS. Similar trends were achieved upon scale-up using the vertical extruder. However, the extrusion process becomes less sensitive with less variability observed as a function of variation in content and drug dissolution. Furthermore increasing the screw speed of the vertical extruder had a greater impact on the loss of crystallinity compared to the horizontal extruder. Overall this paper demonstrates that scale up is feasible from an horizontal 10 mm L/D 20 to a Vertical All in One 10 mm L/D 40 which will allow for a significant saving of materials (especially APIs) during the formulation and process development stages. Furthermore, this study demonstrates that the vertical extruder provides a more robust manufacturing process compared with the horizontal extruder as neither the temperature profile of the barrel nor the screw speed significantly impacted the dissolution rate of the HCQS. This should be of great advantage to the pharmaceutical industry as production rate could be increased or decreased as needed, through an increase or decrease of the screw speed, with minimum and/or no impact on the critical quality attributes of the final product and thus no need for additional bioequivalence studies.

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hal-04993454 , version 1 (17-03-2025)

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Suha M Dadou, Valentyn Mohylyuk, Shu Li, David S Jones, Pascal Boulet, et al.. 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. International Journal of Pharmaceutics, 2021, 605, pp.120818. ⟨10.1016/j.ijpharm.2021.120818⟩. ⟨hal-04993454⟩
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