Industrialization of lipid nanoparticles: From laboratory-scale to large-scale production line

Eur J Pharm Biopharm. 2016 Dec:109:206-213. doi: 10.1016/j.ejpb.2016.10.018. Epub 2016 Oct 25.

Abstract

This work aimed at developing a large-scale modular production line, which referred to coenzyme Q10 loaded-NLC as well as its continuous and scalable emulsification and homogenization process. The production line exhibited good control over the emulsification and homogenization process and enabled the particle size of NLC below 210nm at a throughput of 25kg/h (for lipid solution at a flow rate of 0.4kg/min). Among the several process parameters investigated, the size of the NLC was mainly influenced by the pre-emulsification temperature, homogenization pressure and homogenization. Suitable emulsification temperature (70°C), homogenization pressure (600, 800bar), and homogenization cycle (3, 4cycles) resulted in relatively smaller particles. These results proved that coenzyme Q10, a model active, had been successfully loaded into the NLC. Meanwhile, the large-scale production line can be effectively applied for continuous and modular production of NLC. The line had modern networking features-essential in the Internet age-and a modular design that was easily modified and upgraded. In addition, the long-term stability over 6month was monitored at 30°C and at 40°C to assess a potential effect of the laboratory scale and large scale on stability. All batches at room temperature and below were stable, and only a negligible increase in size was observed.

Keywords: Emulsification temperature; Homogenization cycle; Homogenization pressure; Large-scale; Modular; NLC.

MeSH terms

  • Administration, Topical
  • Automation
  • Biocompatible Materials
  • Centrifugation
  • Drug Carriers / chemistry
  • Drug Design
  • Drug Stability
  • Excipients
  • Humans
  • Hydrogen-Ion Concentration
  • Lipids / chemistry
  • Nanoparticles / chemistry*
  • Particle Size
  • Pressure
  • Technology, Pharmaceutical / methods
  • Temperature
  • Ubiquinone / administration & dosage
  • Ubiquinone / analogs & derivatives*
  • Ubiquinone / chemistry

Substances

  • Biocompatible Materials
  • Drug Carriers
  • Excipients
  • Lipids
  • Ubiquinone
  • coenzyme Q10