Physicochemical properties of lipid emulsions formulated with high-load all-trans-retinoic acid

PDA J Pharm Sci Technol. 2007 Nov-Dec;61(6):461-71.

Abstract

The objective of this study was to formulate high loading with good stability of all-trans retinoic acid (ATRA) lipid emulsion. Lipid emulsions loaded with ATRA were composed of lecithin, medium chain triglyceride and poloxamer-188 or polysorbate-80. The formulation factors in a particular type and amount of oil, emulsifier, and co-emulsifier on the physicochemical properties (i.e., particle size, size distribution, droplets surface charge, pH, percentage yield, drug release, and stability of lipid emulsions) were studied. The particle size of ATRA-loaded lipid emulsions was in the nano-size range of 124.4-378.2 nm with the narrow polydispersity index of 0.04-0.09, which decreased as the amount of co-emulsifiers was increased. The amount of ATRA released from lipid emulsions was operated using a dialysis bag. The receptor medium was ethanol:polysorbate-80:water (10:15:75), adjusted to pH 8.5. ATRA release kinetics in this study were found to follow zero-order kinetics. As the concentration of co-emulsifiers increased, the flux of ATRA released from the lipid emulsions increased. In stability studies, the higher the amount of co-emulsifiers added, the lower the crystallization of ATRA was found. The percentage yield of ATRA was retained at about 70-90% and 60-72% after storage for 60 days at 4 degrees C and 25 degrees C, respectively. These results show a successful incorporation of ATRA into lipid emulsions with high loading capacity and good stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemical Phenomena
  • Chemistry, Pharmaceutical
  • Chemistry, Physical
  • Chromatography, High Pressure Liquid
  • Excipients
  • Fat Emulsions, Intravenous / chemistry*
  • Particle Size
  • Phospholipids / chemistry
  • Poloxamer / chemistry
  • Polysorbates / chemistry
  • Solubility
  • Tretinoin / chemistry*

Substances

  • Excipients
  • Fat Emulsions, Intravenous
  • Phospholipids
  • Polysorbates
  • Poloxamer
  • Tretinoin