In vitro dispersion test that could serve as a predictive method for assessing performance of lipid-based drug delivery systems

A relatively simple in vitro dispersion test using the USP Dissolution Apparatus II filled with 250 ml of dispersion fluid (0.01M HCl) at 37°C and a rotation speed of 50 RPM was used to assess the performance of lipid-based formulations. Solutions of probucol in mixtures with the surfactant Cremophor® EL with four different medium chain lipids (glyceryl monocaprylocaprate, Capmul® MCM EP; glyceryl dicaprylate; glyceryl tricaprylate, Captex® 8000 EP/NF; caprylic/capric triglyceride, Captex® 355 EP/NF) were formulated and filled into Size 00 hard gelatin capsules (~1 g/capsule) for dispersion testing. Drug concentration in the dispersion fluid and the particle size of the dispersed phase as a function of time were measured with, and without, filtration through 0.45 micron filters. All the lipid/surfactant mixtures dispersed in <1 hour (>80%), indicating suitability for their use in immediate-release formulations. The particle size of the unfiltered samples confirmed whether a microemulsion (<250 nm), a very fine emulsion (250-1000 nm) or an emulsion with relatively larger globule sizes (>1000 nm) was formed. The dispersion test developed here could be used to screen different lipid-based formulations for in vitro performance. Justification for using an in vitro dispersion test to predict in vivo performance of lipid-based drug delivery systems has been provided.