Abstract:

Complex pseudo-ternary phase diagrams based on sucrose monolaurate (SE), propylene glycol (PG), and phosphatidylcholine (PC) as the "surfactant phase"; triacetin (TA) and decaglycerol ester (10G1CC) as the "oil phase"; and water as the aq. phase were constructed, into which the authors solubilized the water-insol. drug (sodium diclofenac, Na-DFC). In the authors' previous study the authors demonstrated that the solubilization of Na-DFC in the oil + surfactant phases (prior to dilg. it with water), was 90-fold greater than its dissoln. in water, and that the system was pH-dependent. The greatest Na-DFC solubilization capacity was obtained at pH 7.2. In this study the authors examd. the effect of the solubilization of Na-DFC in a phosphatidylcholine system using DLS, viscosity, elec. cond., SAXS, SD-NMR, and cryo-TEM measurements. It was found that: (1) the system remains micellar after aq. diln. but with greater polydispersity and greater variety of shapes. The authors concluded that the structures in the absence of water (but in the presence of PG) were of direct spherical micelles (∼4 nm) mixed with elongated cylindrical micelles (12-140 nm); (2) the aq. diln. causes fragmentation of the cylinders into smaller spherical micelles; (3) solubilization of Na-DFC behaving like a kosmotropic agent or "structure maker" yields mostly spherical swollen micelles and more ordered systems than in its absence; and (4) Na-DFC is solubilized at the interface of the micelles without swelling the droplets. [on SciFinder(R)]