Effects of Model Drug: Ibuprofen - Optical Microscopy: Injecting SEDDS Into the Aqueous Phase

Supplemental file2

Effects of model drug: Ibuprofen - Optical microscopy: injecting SEDDS into the aqueous phase

We have verified that the effects observed for the placebo formulation in the presence of concentrated glycerol were still present if drug was dissolved in the SEDDS. We selected Ibuprofen as a model drug (Ibuprofen 25, BASF, Germany, batch IB1W0038) and loaded the SEDDS with 6%(w:w) of Ibuprofen. The concentration was selected to be comparable with that of the literature1and because it correspond to the dose usually administered to humans. Furthermore, the concentration used was below the solubility limit which we measured to be 15%(w:w).

Practically, we followed the procedure described in the manuscript and observed under an optical microscope the self-emulsification of the SEDDS via the aqueous phase. Typical images are displayed in Figure 1S.

The self-emulsification of the SEDDS in pure water is very similar without (first column from the left) and with Ibuprofen (second column). In pure water, the SEDDSs appear dark and keep an elongated shape after injection. After some time (typically 30 s to 90 s), phase separation seem to occur with the appearance of a brighter drop. In parallel, a diffusive grey cloud develops, most probably constituted of droplets of SEDDS into water. This behaviour is very different from the one observed with glycerol. Without Ibuprofen (third column from the left) as well as loaded with Ibuprofen (fourth column), the injected SEDDSs appear almost transparent after injection indicating that the refractive index of both phases are quite similar. The injected SEDDSs do not recover a spherical shape and folds are visible at the interface as expected for very low interfacial tension. No phase separation can be identified. The injected SEDDSs break up in a cloud of droplets whose size decrease with time and which diffuse away from the injection point.

From these observations, it appears that the presence of glycerol in the aqueous phase is more critical that the presence of Ibuprofen in the SEDDS. The effects induced by glycerol are thus expected to be relatively robust compared to those of other components, which underlines the applicability of our results.

Reference

1. Mercuri A, Passalacqua A, Wickham MSJ, Faulks RM, Craig DQM, Barker SA. The effect of composition and gastric conditions on the self-emulsification process of ibuprofen-loaded self-emulsifying drug delivery systems: a microscopic and dynamic gastric model study. Pharm Res. 2011;28(7):1540-1551. doi:10.1007/s11095-011-0387-8.