Preparation and structural investigations of colloidal dispersions prepared from cubic monoglyceride-water phases.
Dispersions of bicontinuous cubic monoglyceride-water phases, so-called 'cubosomes', have been proposed as parenteral sustained release delivery systems. For the present study, dispersions of monoolein-rich monoglycerides (MO), with or without purified soya phospholipids (PL), were prepared by equilibration of a MO/(PL)/water cubic phase, subsequent fragmentation with a poloxamer 407 (P407) solution, sonication and homogenization. This yielded systems of very different macroscopic appearance: Almost transparent dispersions, slightly turbid systems, opaque dispersions or milky emulsions. The mean z-average particle diameters ranged from 80 nm to well above 350 nm. Considerable particle growth could be detected in most systems during storage at room temperature. Storage at 5 degrees C resulted in the formation of ointment-like gels, which may be attributed to the crystallization of MO. Freeze-fracture transmission electron micrographs of MO dispersions revealed predominantly spherical particles with a low fracturing tendency. Synchrotron radiation X-ray diffraction indicated that high energy input during disintegration of the cubic phase leads to very complex systems in which particles with a cubic structure and MO/(PL) vesicles may coexist. The characteristic reflections of cubic systems were absent in the diffraction patterns of almost transparent or slightly turbid dispersions. The results indicate a strong dependence of ultrastructure of the dispersions on the preparation parameters.
Pharmacia Oncology Immunology AB, Box 941, S-251 09 Helsingborg, Sweden. britta.siekmann@camurus.ideon.se
Britta
B
Siekmann
Heike
H
Bunjes
Michel H J
MH
Koch
Kirsten
K
Westesen
D002626:Chemistry, Pharmaceutical; D003102:Colloids / Q000737:chemistry; D016503:Drug Delivery Systems; D005989:Glycerides / Q000008:administration & dosage* / Q000737:chemistry*
D003102:Colloids; D005989:Glycerides; C005953:monoolein