title: Development of omega-3 phospholipid-based solid dispersion of fenofibrate for the enhancement of oral bioavailability.
abstract: This research aimed to develop the omega-3 phospholipids based solid dispersion to improve the oral bioavailability of fenofibrate. The omega-3 phospholipids based solid dispersion formulation (OPSD) was prepared by an antisolvent precipitation with immediate freeze-drying and the optimal composition of the formulation was determined as the ratios of sucrose to krill oil of 5:1 (w/w), krill oil to fenofibrate of 1.5:1 (w/w), and antisolvent to solvent of 6:4 (v/v). The developed OPSD formulation was characterized by using scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC), which indicated the crystalline state of fenofibrate in the OPSD. The drug release profiles were also examined at different pHs. The OPSD achieved almost complete dissolution within 15 min, while the untreated powder and physical mixture exhibited minimal dissolution (less than 10% even after 2h). Furthermore, this formulation effectively increased the oral drug exposure in rats, as the Cmax and AUC of fenofibric acid (an active metabolite) were enhanced by approximately 6-7 folds. These results suggest that the OPSD formulation should be promising for improving the oral bioavailability of fenofibrate.
authors.affiliation: BK Plus Project Team, College of Pharmacy, Dongguk University-Seoul, Dongguk-ro-32, Ilsan-Donggu, Goyang, Republic of Korea.
authors.forename: Liang
authors.initials: L
authors.lastname: Yang
authors.affiliation: BK Plus Project Team, College of Pharmacy, Dongguk University-Seoul, Dongguk-ro-32, Ilsan-Donggu, Goyang, Republic of Korea.
authors.forename: Yating
authors.initials: Y
authors.lastname: Shao
authors.affiliation: BK Plus Project Team, College of Pharmacy, Dongguk University-Seoul, Dongguk-ro-32, Ilsan-Donggu, Goyang, Republic of Korea. Electronic address: hkhan@dongguk.edu.
authors.forename: Hyo-Kyung
authors.initials: HK
authors.lastname: Han
mesh_terms: D000818:Animals; D065546:Drug Liberation; D015525:Fatty Acids, Omega-3 / Q000737:chemistry / Q000493:pharmacokinetics; D011345:Fenofibrate / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D000960:Hypolipidemic Agents / Q000737:chemistry / Q000493:pharmacokinetics; D007419:Intestinal Secretions / Q000737:chemistry; D008297:Male; D010743:Phospholipids / Q000737:chemistry / Q000493:pharmacokinetics; D017207:Rats, Sprague-Dawley; D012995:Solubility
chemical_list: D015525:Fatty Acids, Omega-3; D000960:Hypolipidemic Agents; D010743:Phospholipids; C006012:fenofibric acid; D011345:Fenofibrate
keywords: Antisolvent; Bioavailability; Dissolution; Fenofibrate; Omega-3 phospholipids