Suitability of phosphatidylcholine-based formulations for liquid filling in hard capsules

Eur J Pharm Sci. 2020 Oct 1:153:105470. doi: 10.1016/j.ejps.2020.105470. Epub 2020 Jul 16.


The current study aimed to evaluate whether phosphatidylcholine-based formulations have suitable properties for liquid filling in hard capsules. Liquid or semisolid formulations were obtained with Miglyol 812 (medium chain triglycerides) or Softisan 378 (semisolid hard fat), respectively, in combination with three different phospholipids (Phospholipon 90 G, Lipoid S 75 or Lipoid S LPC 80) and ethanol. Suitability for the filling process was evaluated by rheological characterization and stringing tests. Liquid and semisolid mixtures with Lipoid S 75 or Phospholipon 90 G (also with addition of Lipoid S LPC 80) exhibited appropriate viscosity at the respective filling temperatures. Liquid mixtures with up to 60% Phospholipon 90 G broke cleanly from the needle during filling simulations. A higher fraction of phospholipid led to stringing which could be reduced by addition of ethanol. The hygroscopicity of the formulations was investigated as was their compatibility with different capsule materials with regard to their impact on capsule brittleness and integrity. Gelatin capsules became brittle due to the hygroscopic properties of phosphatidylcholine-based mixtures whereas hydroxypropyl methylcellulose capsules were compatible with a wide range of formulations. After aeration with nitrogen, the formulations exhibited acceptable stability against oxidation.

Keywords: HPMC capsules; Liquid-fill formulations; Phospholipids; Self-emulsifying drug delivery systems (SEDDS); Stringing; Thermosoftening formulations.

MeSH terms

  • Capsules
  • Drug Compounding
  • Gelatin*
  • Hypromellose Derivatives
  • Viscosity


  • Capsules
  • Hypromellose Derivatives
  • Gelatin