Emulsion Type New Vehicle Available for Preclinical and Clinical Trials: Stability of Characteristics of Particle Size Distribution of New Vehicle.

We developed a new vehicle system that can be encapsulated in soft gelatin capsules and utilized both in preclinical and clinical trials. The particle size distribution of the basic formulation (PEG 400: water: medium chain triglyceride (Miglyol 810®): polyoxyethylene (20) cetylether (BC-20TX®) =73.95 : 13.05 : 10 : 3) of the new vehicle system was very narrow and the particle size was smaller than 1μm immediately after preparation. The stability of the new vehicle was evaluated at room temperature, based on changes in the particle size distribution up to 12 days after preparation. The volume frequency profile of the particle size distribution became slightly broader after 1-day storage, thereafter remained constant during 5-day storage, and was again broadened and shifted to a range of lager diameters after 12 days. In the case of a formulation enriched with a hydrophobic phase (20 w/w% of medium chain triglyceride), the result was similar to that for the above basic formulation. When polyoxyethylene (20) cetylether (surfactant) content was decreased to 1.5 w/w%, however, the volume frequency profile after 12 days was further broadened, and two peaks were observed. Similar results were obtained in terms of parameters calculated from the cumulated frequency profiles of the particle size distribution. These results suggest that this new vehicle system can contain as much as 20 w/w% of hydrophobic phase, and requires 3 w/w% of surfactant (1.5 w/w% is insufficient). When polyoxyethylene (20) cetylether was partially (10 w/w% of total surfactant) replaced with milk fat globule membrane (MFGM) for each of above three formulations, the volume frequency profile after 12 days was comparable with or narrower than that of the original one. It seems that MFGM is a co-surfactant useful to maintain the particle size distribution of new vehicles, preventing coagulation of particles.