In Vitro Dispersion Test Can Serve as a Predictive Method for Assessing Performance of Lipid-based Drug Delivery Systems

Abstract

A relatively simple in vitro dispersion test using the USP Dissolution Apparatus II with 250 mL of dispersion fluid (0.01M HCl) at 37°C and the rotation speed 50 RPM was used to assess the performance of lipid-based formulations. Solutions of probucol in mixtures of the surfactant Cremophor EL with four different medium chain lipids (glycerol monocaprylocaprate, Capmul MCMEP; glycerol dicaprylate; glycerol tricaprylate, Captex 8000EP/NF; caprylic/capric triglyceride, Captex 355 EP/NF) were formulated and filled in Number 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 without and with filtration through filters of 0.45 micron pore size. All lipid/surfactant mixtures used dispersed (≥80%) in <1 h, indicating their suitability for the development of immediate-release formulations. The particle size of unfiltered samples indicated whether microemulsion (<250 nm), very fine emulsion (250-1000 nm) or emulsion with relative larger sizes (>1000 nm) were formed. The dispersion test developed is capable of screening different lipid-based formulations for in vitro performance. Justification is also provided for using the dispersion test as a predictive method for assessing in vivo performance of such formulations.