title: Investigation of a nanosuspension stabilized by Soluplus® to improve bioavailability.
abstract: The purpose of this work was to explore the feasibility of using Soluplus(®) in preparing a fenofibrate (FBT) nanosuspension adopting wet media milling technology. HPMC and Soluplus(®) were used as stabilizers to prepare FBT/HPMC nanosuspension (F1) and FBT/Soluplus(®) nanosuspension (F2), respectively. The nanosuspensions were subjected to evaluations involving particle size, dissolution, preliminary stability and pharmacokinetic behavior. A marked reduction in particle size was achieved by nanosuspensions (from 17.55 μm to 642 nm (F1) and 344 nm (F2)). The nanosuspensions displayed almost complete dissolution while percentages of 30% and 13% were obtained by physical mixtures and coarse FBT separately. Soluplus(®) could stabilize the nanosuspension more effectively due to a weaker Ostwald ripening effect resulting from a slower diffusion of micelles formed by Soluplus(®) entrapping dissolved FBT than FBT exposed to pure water directly. In the in vivo evaluation, larger AUC0-72h and Cmax, and shorter Tmax were obtained by the nanosuspensions. Significant differences were observed between the physical mixtures. The phenomenon of double peaks was present in this study. The major factor may be the multiple absorption sites of FBT. The current work indicated that Soluplus(®) is well suited for preparation of a nanosuspension with good stability and improved dissolution and bioavailability.
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, Wen Hua Road No. 103, Shenyang 110016, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, Wen Hua Road No. 103, Shenyang 110016, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Teng
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, Wen Hua Road No. 103, Shenyang 110016, China.
authors.forename: Puxiu
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, Wen Hua Road No. 103, Shenyang 110016, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Tian
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, Wen Hua Road No. 103, Shenyang 110016, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, Wen Hua Road No. 103, Shenyang 110016, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, Wen Hua Road No. 103, Shenyang 110016, China.
authors.forename: Keru
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, Wen Hua Road No. 103, Shenyang 110016, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, Wen Hua Road No. 103, Shenyang 110016, China. Electronic address: tanglab@126.com.
authors.forename: Xing
authors.initials: X
authors.lastname: Tang
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D005240:Feasibility Studies; D011345:Fenofibrate / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D065347:Hypromellose Derivatives / Q000737:chemistry; D008297:Male; D008823:Micelles; D053758:Nanoparticles; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011145:Polyvinyls / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013535:Suspensions
chemical_list: D005079:Excipients; D008823:Micelles; D011145:Polyvinyls; D013535:Suspensions; C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; D065347:Hypromellose Derivatives; D011092:Polyethylene Glycols; D011345:Fenofibrate
keywords: Bioavailability; Fenofibrate; Nanosuspension; Soluplus(®); Stability; Wet media milling