title: Studies on pharmacokinetics and tissue distribution of bifendate nanosuspensions for intravenous delivery.
abstract: It is reported that the nanosuspension is one of the promising formulations for poorly water-soluble drugs. In order to enhance the in vitro and in vivo behaviours of DDB (bifendate), DDB-NSP (DDB nanosuspensions) have been produced by the precipitation-combined microﬂuidization method. The optimized DDB-NSP were transformed into dry powders by freeze-drying and then investigated by transmission electron microscopy, laser diffraction and X-ray diffraction (XRD) experiments. Next, the pharmacokinetics and biodistribution of DDB-NSP and DDB-Sol (DDB solution) were carried out. XRD experiments manifested that the crystalline state of DDB was preserved after the size reduction process. An accelerated dissolution velocity and increased saturation solubility could be shown for the DDB-NSP. Compared with DDB-Sol, DDB-NSP exhibited a markedly different pharmacokinetic property with a 17.18-fold increase in AUC(0-∞). Meanwhile, the tissue distribution demonstrated that DDB-NSP were mainly uptaken by RES organs particularly by liver. These results supported the fact that nanosuspension, as a promising intravenous drug-delivery system for DDB, could be developed as an alternative to the conventional DDB preparations.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shandong University, 44 Wenhua Xilu, Jinan 250012, PR China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.forename: Dianrui
authors.initials: D
authors.lastname: Zhang
authors.forename: Cunxian
authors.initials: C
authors.lastname: Duan
authors.forename: Lejiao
authors.initials: L
authors.lastname: Jia
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Xie
authors.forename: Dandan
authors.initials: D
authors.lastname: Zheng
authors.forename: Feihu
authors.initials: F
authors.lastname: Wang
authors.forename: Guangpu
authors.initials: G
authors.lastname: Liu
authors.forename: Leilei
authors.initials: L
authors.lastname: Hao
authors.forename: Xueshun
authors.initials: X
authors.lastname: Zhang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000737:chemistry / Q000493:pharmacokinetics*; D002152:Calorimetry, Differential Scanning; D016503:Drug Delivery Systems; D004355:Drug Stability; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D046210:Microfluidic Analytical Techniques; D011817:Rabbits; D012995:Solubility; D013535:Suspensions; D014018:Tissue Distribution; D014961:X-Ray Diffraction
chemical_list: D001713:Biphenyl Compounds; D013535:Suspensions; C465548:bifendate