*2.3. Lipid Solubility Studies*

The equilibrium solubility (Seq) of FEN in Capmul PG8, Captex 300, and Capmul MCM was determined in triplicate at 25, 40, and 60 ◦C. An excess of FEN was added to centrifuge tubes containing approximately 0.5 g lipid. The tubes were vortex mixed for 10–20 s to aid drug dissolution and placed on a rotator in an oven at the required temperature. After 24 h, samples were centrifuged at 44,800 rcf for 30 min at the required temperature to precipitate any undissolved drug. Methanol was used to extract the dissolved drug from the supernatant and was appropriately diluted with mobile phase prior to HPLC analysis. Samples were vortexed and returned to the rotator in the oven and analyzed every 24 h until equilibrium solubility was reached. This was indicated by <10% change in consecutive solubility measurements.

Due to a temperature limit on the centrifuge, centrifugation was not possible at 60 ◦C. Therefore, samples were left in the oven to allow for undissolved drug to settle as a pellet, and aliquots were carefully taken from supernatant. This method was previously validated [29], and an acceptable standard deviation was attained.
