Table 3

Overview of test methods for assessment of physical compatibility between total parenteral nutrition (TPN) and parenteral drugs and the acceptance criteria applied8

Methods for detection of potential precipitates in mixed samples
(drug+TPNaq)
Acceptance criteria/points to consider
Sub-visual particle counting by light obscurationa Particle counts <1000–2000/mL ≥0.5 µm,8 and large particles not exceeding Ph.Eur. limits for large volume parenterals14
Turbidity measured by turbidimeterb Turbidity <0.20–0.30 FNU (taking into consideration background turbidity of unmixed samples)8
Visual examination against black background with Tyndall beamsc No signs of visible particles or Tyndall effect8 15
pH measured by pH meterd Evaluation of risk of precipitation of drug and/or calcium phosphate.
Methods for assessment of emulsion stability in mixed samples
(drug+TPN)
Acceptance criteria/points to consider
MDD measurements; laser diffractione V.W. MDD should be <500 nm
Size fraction (%) >5 µm should be zero16
PFAT5 calculated based on droplet size measurements from light obscurationa PFAT5 <0.40%16 17
pH measured by pH meterd pH <5.5 might be an indication of increased risk of emulsion destabilisation17
  • a, Accusizer 780 Optical Particle Sizer, Nicomp PSS, Santa Barbara, USA.

  • b, 2100Qis Turbidimeter, Hach Lange GmbH, Düsseldorf, Germany.

  • c, Fibreoptic light source (Schott KL 1600 LED, Mainz, Germany) and red pocket laser pointer (630–650 nm, max output <1 mW).

  • d, Metrohm 744 pH meter, Metrohm AG, Herisau, Switzerland.

  • e, Mastersizer 2000 and Hydro 2000G sample dispersion unit, Malvern Instruments, Worcestershire, UK.

  • PFAT5, volume weighted percentage of fat droplets above 5 µm.

  • FNU, Formazin nephelometry units.

  • V.W. MDD, volume weighted mean droplet size.