Formation and stability of the dispersed particles composed of retinoic acid, sesame oil and phosphatidylcholine.
All trans-retinoic acid (RA) was dispersed by sonication with soybean phosphatidylcholine (PC). The particle size in the dispersion was increased to 240 nm up to the RA mol fraction range (X(RA)) of 0.4. At X(RA)=0.5, the RA/PC mixture was difficult to disperse and the macroscopic oil/water phase separation was observed. On the other hand, by the addition of sesame oil (SO) to RA (molar ratio of RA:SO=1:1), stable aqueous dispersions (diameter: 40-80 nm) were obtained in the mol fraction range RA and SO mixture (X(M)) of 0.1-0.8. In order to clarify these dispersal mechanism, the dispersed particles were characterized and the interaction among RA, SO and PC was investigated using several physicochemical techniques. The trapped aqueous volume inside the RA/PC particles was determined using the aqueous space marker, calcein and it was increased with the addition of RA into small unilamellar vesicles of PC. On the other hand, that of RA/SO/PC particles was decreased remarkably with increase in X(M) and the decline in the fraction of vesicular particles was also confirmed by fluorescence quenching of N-dansylhexadecylamine in the PC membrane by the addition of the quencher CuSO(4). These results indicate that the interaction of RA with PC bilayers and the structure of RA/PC mixture will be changed by the addition of SO.
Asai
Y
Y
Formulation Research Laboratory, Kawashima, Eisai Co. Ltd., Takehaya-machi, Kawashima-cho, Hashima-gun, Gifu, Japan. 06968@ecl.eisai.co.jp
Watanabe
S
S
D000465:Algorithms; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D019327:Copper Sulfate / Q000737:chemistry; D005079:Excipients; D008027:Light; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry*; D011312:Pressure; D012542:Scattering, Radiation; D012715:Sesame Oil / Q000737:chemistry*; D012995:Solubility; D013050:Spectrometry, Fluorescence; D014212:Tretinoin / Q000008:administration & dosage* / Q000737:chemistry
D005079:Excipients; D010713:Phosphatidylcholines; D014212:Tretinoin; D012715:Sesame Oil; D019327:Copper Sulfate