title: Influence of drug physicochemical properties on absorption of water insoluble drug nanosuspensions.
abstract: In order to investigate the influence of drug physicochemical properties on bioavailability of water insoluble drug nanosuspensions, five drug nanosuspensions were prepared using high pressure homogenization. These nanosuspensions were similar in particle size and same in stabilizer. Differential scanning calorimetry and powder X-ray diffraction analysis showed the crystalline state of the freeze dried nanocrystals did not change. In vitro dissolution test in fasted state simulated intestinal fluid (FaSSIF) and in vivo bioavailability study in rats demonstrated that the nanosuspensions had higher dissolution rate and higher AUC0-t and the ratios of dissolvednano/dissolvedmicro in 120 min were well correlated with the ratios of AUC0-t nano/AUC0-t micro. Correlation analysis between drug physicochemical properties and AUC0-t nano was performed and four-grid interpolation method was employed for interpolation and smooth surface fitting to give a visible trend. The results revealed that drug with smaller melting point, logP value around 5 and polar surface area value in the range of 50-60 would gain higher AUC0-t nano and accordingly better absorption of its nanosuspension. Melting point, logP and polar surface area were factors that influence the absorption of drug nanosuspensions in this study.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Quan
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Yaqiong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cheng
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Cun
authors.affiliation: School of Medical Instrument, Shenyang Pharmaceutical University, Shenyang, China. Electronic address: xrwlove@163.com.
authors.forename: Rongwu
authors.initials: R
authors.lastname: Xiang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China. Electronic address: fangliang2003@yahoo.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Fang
mesh_terms: D020003:1-Octanol / Q000737:chemistry; D000042:Absorption; D015766:Albendazole / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D011345:Fenofibrate / Q000737:chemistry / Q000493:pharmacokinetics; D017964:Itraconazole / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D004364:Pharmaceutical Preparations / Q000737:chemistry; D033362:Powder Diffraction; D011341:Probucol / Q000737:chemistry / Q000493:pharmacokinetics; D011744:Pyrimidinones / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013499:Surface Properties; D013535:Suspensions; D044005:Tetrahydroisoquinolines / Q000737:chemistry / Q000493:pharmacokinetics; D044366:Transition Temperature; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D004364:Pharmaceutical Preparations; D011744:Pyrimidinones; D013535:Suspensions; D044005:Tetrahydroisoquinolines; D014867:Water; D017964:Itraconazole; C108798:YH 1885; D015766:Albendazole; D020003:1-Octanol; D011341:Probucol; D011345:Fenofibrate
keywords: Bioavailability; Correlation analysis; Dissolution; Drug physicochemical property; Nanosuspension