Formation and stability of the dispersed particles composed of retinyl palmitate and phosphatidylcholine.
The purpose of this study was to develop an intravenous formulation composed of retinyl palmitate (RP) for the treatment of cancer. RP was dispersed with soybean phosphatidylcholine (PC) using sonication and the dispersal mechanism was evaluated by characterizing the dispersed particles using dynamic light-scattering, fluorescence spectroscopy, and surface monolayer techniques. The dispersions in the RP mole fraction range of 0.1-0.8 were stable at room temperature for 3 days. A limited amount of RP was incorporated into PC bilayer membranes (approximately 3 mol%). The excess RP separated from the PC bilayers was stabilized as emulsion particles by the PC surface monolayer. When the PC content was less than the solubility in RP, the PC monolayer did not completely cover the hydrophobic RP particle surfaces and separation into oil/water occurred. The miscibility between RP and PC and the lipid composition were critically important for the stability of the dispersed particles (coexistence of emulsion particles [surface monolayer of PC + core of RP] with vesicular particles [bilayer]) of the lipid mixtures.
Asai
Y
Y
Formulation Research Laboratory, Kawashima, Eisai Co., Ltd., Gifu, Japan.
Watanabe
S
S
D016588:Anticarcinogenic Agents / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004224:Diterpenes; D004355:Drug Stability; D004655:Emulsions; D007262:Infusions, Intravenous / Q000379:methods*; D008567:Membranes, Artificial; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry*; D000084562:Retinyl Esters; D013057:Spectrum Analysis; D013499:Surface Properties; D013696:Temperature; D014465:Ultrasonics; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000737:chemistry
D016588:Anticarcinogenic Agents; D004224:Diterpenes; D004655:Emulsions; D008567:Membranes, Artificial; D010713:Phosphatidylcholines; D000084562:Retinyl Esters; D014801:Vitamin A; C014794:retinol palmitate