In Vitro and Ex Vivo Investigation of the Impact of Luminal Lipid Phases on Passive Permeability of Lipophilic Small Molecules Using PAMPA

Purpose Evaluate the impact of luminal micellar phase on passive permeability of five lipophilic (1.9 ≤ clogP ≤ 9.0) small molecules using biorelevant media and evaluate the impact of luminal coarse lipid particles on danazol permeability after oral administration of a triglyceride solution to fed adults using PAMPA.

Permeability of carbamazepine, furosemide, danazol, and Compound A was evaluated using Prisma™ HT, FaSSIF-V2, and FeSSIF-V2 in the donor compartment. Compound B could not be tested using Prisma™ HT, due to negligible solubility. Individual intestinal aspirates collected after administration of danazol solution in the olive oil portion of a meal and corresponding micellar phases were subjected to PAMPA. Commercially available Acceptor Sink Buffer was used in all cases.

Unlike with furosemide (under constant pH) and Compound B, permeability of carbamazepine, danazol, and Compound A steadily decreased in the presence of increasing micelle concentration of media. Danazol permeability from aspirates was reduced compared to that from micellar phases; fluxes were similar.

Using PAMPA, the impact of luminal micellar phase on passive permeability of lipophilic molecules varies with the molecule. After administration of a triglyceride solution of danazol, high danazol concentrations in coarse lipid particles balance in terms of drug flux the reduced permeability. Similar content being viewed by others

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Miller JC, Miller JN. Statistics for analytical chemistry. New York: Wiley; 1984. ACKNOWLEDGMENTS AND DISCLOSURES Parts of this manuscript have been presented at AAPS Αnnual Μeeting (Chicago, 2012), at the First Greek Congress of Pharmaceutical Sciences (Athens, 2012), and at the 15th Hellenic Symposium on Medicinal Chemistry (Athens, 2012). Partial financial support by the State Scholarships Foundation, Greece, and the Federal Commission for Scholarships for Foreign Students (ESKAS), Switzerland, is greatly appreciated. The authors would like to thank Dr N. Aligiannis and Ms E. Chaita, Department of Pharmacognosy and Chemistry of Natural Products, Faculty of Pharmacy, National and Kapodistrian University of Athens for their help with the plate readings. Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Markopoulos, C., Imanidis, G., Vertzoni, M. et al. In Vitro and Ex Vivo Investigation of the Impact of Luminal Lipid Phases on Passive Permeability of Lipophilic Small Molecules Using PAMPA. Pharm Res 30, 3145–3153 (2013). https://doi.org/10.1007/s11095-013-1141-1 Received: Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s11095-013-1141-1