TY - JOUR
T1 - Biorelevant media simulating fed state intestinal fluids
T2 - colloid phase characterization and impact on solubilization capacity
AU - Kleberg, Karen
AU - Jacobsen, Freja
AU - Fatouros, Dimitris G.
AU - Müllertz, Anette
PY - 2010/8
Y1 - 2010/8
N2 - The purpose of the present study was to study the impact of free fatty acid and monoglyceride level and ratio on the nanostructural composition and solubilizing capacity of media simulating fed state intestinal fluids (SIFs). SIFs, without or with oleic acid/monoolein (OA/MO) in ratios of 2:1 or 6:1 were composed and characterized by surface tension, dynamic light scattering, and cryogenic transmission electron microscopy. Additionally solubilizing capacities towards three poorly water-soluble compounds: danazol, fenofibrate, and cinnarizine, were assessed. The surface tension of the media was not affected by the OA/MO ratio but only determined by the total surfactant concentration. The media with no lipolysis products only contained micelles, whereas media with lipolysis products also contained vesicles and other colloidal structures. The structures in the 6:1 media were more numerous and more well-defined regarding shape and size. The nanostructural composition of the media did influence the solubilizing capacity toward fenofibrate and cinnarizine, but not toward danazol. The relative composition of SIFs is important for the solubilizing capacity of some drug compounds. The findings in this study suggest that the affinity of the drug to the different colloidal structures is determining for the solubility of the compound in the media.
AB - The purpose of the present study was to study the impact of free fatty acid and monoglyceride level and ratio on the nanostructural composition and solubilizing capacity of media simulating fed state intestinal fluids (SIFs). SIFs, without or with oleic acid/monoolein (OA/MO) in ratios of 2:1 or 6:1 were composed and characterized by surface tension, dynamic light scattering, and cryogenic transmission electron microscopy. Additionally solubilizing capacities towards three poorly water-soluble compounds: danazol, fenofibrate, and cinnarizine, were assessed. The surface tension of the media was not affected by the OA/MO ratio but only determined by the total surfactant concentration. The media with no lipolysis products only contained micelles, whereas media with lipolysis products also contained vesicles and other colloidal structures. The structures in the 6:1 media were more numerous and more well-defined regarding shape and size. The nanostructural composition of the media did influence the solubilizing capacity toward fenofibrate and cinnarizine, but not toward danazol. The relative composition of SIFs is important for the solubilizing capacity of some drug compounds. The findings in this study suggest that the affinity of the drug to the different colloidal structures is determining for the solubility of the compound in the media.
KW - solubilization, biorelevant media, Cryo-TEM, poorly soluble drug compounds
U2 - 10.1002/jps.22122
DO - 10.1002/jps.22122
M3 - Journal article
C2 - 20564382
SN - 0022-3549
VL - 99
SP - 3522
EP - 3532
JO - Journal of Pharmaceutical Sciences
JF - Journal of Pharmaceutical Sciences
IS - 8
ER -