Optimizing surfactant content to improve oral bioavailability of ibuprofen in microemulsions: just enough or more than enough?

Int J Pharm. 2014 Aug 25; 471(1-2):276-84.IJ

Microemulsions show excellent potential as drug delivery systems, but the surfactants used to prepare them can cause side effects. Researchers have explored various strategies to expand microemulsion area and thereby reduce the surfactant content necessary, but how these strategies affect drug oral bioavailability has not been investigated in detail. Microemulsions were prepared using 16% or 24% mixed surfactant Tween 80-Cremophor EL-PEG400 (1:1:2) and either 6% caprylic/capric triglyceride oil (GTCC) or 6% or 15% mixed oil (Maisine™ 35-1 with GTCC). Some microemulsions contained just enough surfactant based on ternary phase diagrams, while others had excess surfactant. All empty and ibuprofen-loaded microemulsions were clear or translucent with a slight blue color, and they remained stable after dilution and centrifugation. In experiments with rats, oral bioavailability (AUC0⟶t) of ibuprofen in the microemulsions was similar for the different formulations (6779.0-7413.3 min μg/mL) and significantly higher than that of an ibuprofen suspension (4830.9 min μg/mL). The different formulations behaved similarly in a cellular uptake assay with Caco-2 cells. These results suggest that excess surfactant does not increase oral bioavailability or cellular uptake of ibuprofen. Therefore, to minimize side effects, using just enough surfactant to ensure microemulsion stability and drug solubility may be an appropriate strategy.