title: Comparative studies of the in vitro dissolution and in vivo pharmacokinetics for different formulation strategies (solid dispersion, micronization, and nanocrystals) for poorly water-soluble drugs: A case study for lacidipine.
abstract: Different formulation strategies have been proposed for poorly water-soluble drugs. The objective of this study is to give an in vitro and in vivo comparison of a solid dispersion, micronization, and nanocrystals, with lacidipine as a model substance. Micronized lacidipine was obtained by jet milling, and nanocrystals were prepared by bead milling. The d50 for the microcrystals (11,200 nm) was about 20 times larger than that for nanocrystals (623 nm). Both colloidal dispersions maintained a crystalline state after milling. Lacipil(®), lacidipine solid dispersion, was purchased from GlaxoSmithKline. It exhibited a much higher in vitro dissolution profile than both the micronized and nanonized tablets while the micronized and nanonized tablets showed approximately a 1.30- and 2.05-fold increase in AUC(0-24 h) compared with Lacipil(®), respectively. Among the three formulation approaches, Lacipil(®) (solid dispersion) exhibited highest dissolution profile, while nanocrystals produced the greatest increase in oral bioavailability.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: graham_pharm@aliyun.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Fang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Jingbo
authors.initials: J
authors.lastname: Shao
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Mengran
authors.initials: M
authors.lastname: Guo
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Liaoning Institute for Drug Control, Shenyang 110023, China.
authors.forename: Mo
authors.initials: M
authors.lastname: Li
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
authors.affiliation: School of Medical Devices, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: zhaiyinglei@aliyun.com.
authors.forename: Yinglei
authors.initials: Y
authors.lastname: Zhai
mesh_terms: D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D066298:In Vitro Techniques; D008855:Microscopy, Electron, Scanning; D010599:Pharmacokinetics; D033362:Powder Diffraction; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared
keywords: Dissolution; Lacidipine; Micronization; Nanocrystals; Oral bioavailability; Solid dispersion