Development of a compounded propofol nanoemulsion using multiple non-invasive process analytical technologies

T Rooimans, M Damen, C M A Markesteijn, C C L Schuurmans, N H C de Zoete, P M van Hasselt, W E Hennink, C F van Nostrum, M Hermes, R Besseling, H Vromans

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Abstract

Propofol is the preferred anaesthetic for induction and maintenance of sedation in critically ill mechanically ventilated COVID-19 patients. However, during the outbreak of the COVID-19 pandemic, regular supply chains could not keep up with the sudden increase in global demand, causing drug shortages. Propofol is formulated as an oil-in-water emulsion which is administered intravenously. This study explores the extemporaneous preparation of a propofol emulsion without specialized manufacturing equipment to temporally alleviate such shortages. A commercially available lipid emulsion (IVLE, SMOFlipid 20 %), intended for parenteral nutrition, was used to create a propofol loaded nanoemulsion via addition of liquid propofol drug substance and subsequent mixing. Critical quality attributes such as mean droplet size and the volume-weighted percentage of large-diameter (>5µm) droplets were studied. The evolution of droplet size and propofol distribution was monitored in situ and non-destructively, maintaining sterility, using Spatially Resolved Dynamic Light Scattering and Near Infrared Spectroscopy, respectively. Using response surface methodology, an optimum was found for a 4 % w/v propofol formulation with a ∼15 min mixing time in a flask shaker at a 40° shaking angle. This study shows that extemporaneous compounding is a viable option for emergency supply of propofol drug product during global drug shortages.

Original languageEnglish
Article number122960
JournalInternational Journal of Pharmaceutics
Volume640
Early online date13 Apr 2023
DOIs
Publication statusPublished - 10 Jun 2023

Keywords

  • Compounding
  • COVID-19
  • Drug shortage
  • Parenteral lipid nano-emulsion
  • Propofol

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