title: A potent preparation method combining neutralization with microfluidization for rebamipide nanosuspensions and its in vivo evaluation.
abstract: BACKGROUND
  Rebamipide (REB) is classified as a Biopharmaceutics Classification System (BCS) Class-IV compound with poor aqueous solubility and poor permeability. The local concentration in the mucosa makes REB exhibiting the therapeutic activities, and the strategy of increasing the dissolution rate has the possibility to improve the oral gastrointestinal (GI) distribution when using REB nanosuspensions.
  
  
  OBJECTIVE
  The purpose of this work was to prepare REB nanosuspensions (REB-NSs) by combining neutralization with microfluidization to improve its dissolution rate and orally pharmacokinetic properties.
  
  
  METHODS
  The feasibility of using acid-base neutralization and microfluidization to prepare REB-NSs was studied, and the preparation was optimized by central composite design (CCD). Physical states were characterized by using some technical methods, while the plasma drug concentration and GI distribution in rodents were determined.
  
  
  RESULTS
  The experimental results identified a formulation with 10 mg/mL REB, 0.9% (w/v) Lutrol F127, and 0.6% (w/v) Kollidon 90F. The dissolution rate of the dried REB-NSs was faster than that of Mucosta(®) tablets in different media, and the pharmacokinetic study showed a slight increase (1.3-fold and 1.1-fold) in the AUC0-12 h compared with unprocessed conventional suspensions (CSs) and solutions. Also, the GI distribution of REB-NSs improved compared with REB-CSs, and this would be preferable to assist in protecting GI mucosa.
  
  
  CONCLUSIONS
  The REB-NSs prepared by the combining method exhibited a higher plasma drug concentration and superior GI distribution, thereby demonstrating positive results for preparing nanosuspensions of local effective BCS IV drugs with pH dependence such as REB by this method.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, P.R.China.
authors.forename: Yijie
authors.initials: Y
authors.lastname: Shi
authors.forename: Meijuan
authors.initials: M
authors.lastname: Zou
authors.forename: Yue
authors.initials: Y
authors.lastname: An
authors.forename: Zhaoshuai
authors.initials: Z
authors.lastname: Ji
authors.forename: Ping
authors.initials: P
authors.lastname: Gao
authors.forename: Gang
authors.initials: G
authors.lastname: Cheng
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D000897:Anti-Ulcer Agents / Q000737:chemistry*; D041981:Gastrointestinal Tract / Q000378:metabolism; D008297:Male; D051379:Mice; D046210:Microfluidic Analytical Techniques; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D015363:Quinolones / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013535:Suspensions; D014961:X-Ray Diffraction
chemical_list: D000897:Anti-Ulcer Agents; D015363:Quinolones; D013535:Suspensions; C052785:rebamipide; D000409:Alanine