title: Enhanced dissolution and oral bioavailability of aripiprazole nanosuspensions prepared by nanoprecipitation/homogenization based on acid-base neutralization.
abstract: In this study, aripiprazole (APZ), a weak alkaline drug with pH-dependent solubility, was selected as model drug to examine the feasibility of preparing nanosuspensions using nanoprecipitation/homogenization technique based on acid-base neutralization. The related substances in nanosuspensions prepared under optimal conditions were slightly increased as compared with APZ raw material. The resultant APZ nanosuspensions showed a mean particle size of 350 nm with polydispersion index (PI) value of 0.20. Good physical stability was kept for over 40 days. SEM observation showed the morphology of oval crystals with rough surface. Nanosuspensions significantly increased the solubility as well as the dissolution of APZ due to the decreased particle size. Differential scanning calorimetry and powder X-ray diffractometry confirmed the crystallinity of APZ in nanosuspensions. APZ nanosuspensions got maximum absorption rate and extent comparing with APZ commercial tablet and suspensions with relative bioavailability of 123.43 ± 12.98% and 171.41 ± 14.62%, respectively. This technique has the potential to prepare nanosuspensions of insoluble drugs with pH-dependent solubility.
authors.affiliation: School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery of Ministry of Education and PLA, Shanghai, 201203, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Liu
authors.forename: Ruyue
authors.initials: R
authors.lastname: Lian
authors.forename: Siji
authors.initials: S
authors.lastname: Zheng
authors.forename: Zongning
authors.initials: Z
authors.lastname: Yin
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D000068180:Aripiprazole; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D011232:Chemical Precipitation; D004285:Dogs; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D008297:Male; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D010879:Piperazines / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D033362:Powder Diffraction; D015363:Quinolones / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D012995:Solubility; D014961:X-Ray Diffraction
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; D000068180:Aripiprazole