Combined effects of the drug distribution and mucus diffusion properties of self-microemulsifying drug delivery systems on the oral absorption of fenofibrate

Autor: Yusuke Tanaka, Kenjirou Higashi, Yushi Sunazuka, Kunikazu Moribe, Keisuke Ueda
Rok vydání: 2018
Předmět:
Zdroj: International Journal of Pharmaceutics. 546:263-271
ISSN: 0378-5173
DOI: 10.1016/j.ijpharm.2018.05.031
Popis: We present the absorption improvement mechanism of fenofibrate (FFB), a Biopharmaceutics Classification System (BCS) class II drug, from self-microemulsifying drug delivery systems (SMEDDS), centered on improving the diffusion of FFB through the unstirred water layer (UWL). Four SMEDDS formulations containing Labrafac™ lipophile WL 1349 (WL1349) or Labrafil® M 1944CS (M1944) oils and NIKKOL HCO-40 (HCO40) or NIKKOL HCO-60 (HCO60) surfactants were prepared. Every SMEDDS formulation formed microemulsion droplets of approximately 30 nm. In vitro tests showed that the microemulsion droplets containing M1944 had relatively small FFB solubilization capacities, causing larger amounts of FFB to be dissolved in the bulk water phase, compared to the droplets containing WL1349. The diffusivity of the microemulsion droplets through the mucin solution layer was enhanced when using HCO40 compared to HCO60. The oral absorption in rats was the highest when using the SMEDDS formulation containing M1944 and HCO40. High FFB distribution in the bulk water phase and fast diffusion of microemulsion droplets through the mucus layer contributed to the efficient delivery of FFB molecules through the UWL to the epithelial cells, leading to enhanced FFB absorption.
Databáze: OpenAIRE
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