title: Development and optimization of chemically stable lipid microspheres containing flunarizine.
abstract: OBJECTIVE
  The purpose of this study is to develop an appropriate dispersion system containing flunarizine, and most of all, to improve the chemical stability of flunarizine.
  
  
  METHODS
  In this study, a higher incubation temperature (60 degrees C), to induce a faster chemical degradation, was adopted to optimize a better vehicle, an appropriate pH value, and an effective antioxidant system for flunarizine.
  
  
  RESULTS
  The chemical stability of flunarizine was improved significantly in lipid microspheres (LMs) compared with the aqueous solution. The optimal formulation of LMs for flunarizine at pH 8.0 is composed of (w/v): flunarizine 0.1%, dl-alpha-tocopherol 0.1%, medium-chain triglyceride 5%, long-chain triglyceride 5%, soybean lecithin 1.8%, poloxamer 188 0.4 %, Tween-80 0.2%, glycerol 2.5% and l-cysteine 0.05%, Na(2)SO(3) 0.15%, and EDTA 0.01%.
  
  
  CONCLUSIONS
  The long-term stability investigation, stored at 10 +/- 2 degrees C and 25 +/- 2 degrees C for 6 months, witnessed the better chemical stability of flunarizine in LMs. An intravenous delivery system of LMs for flunarizine focusing on a better chemical stability of flunarizine has been successfully developed and optimized.
authors.affiliation: Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Na
authors.initials: N
authors.lastname: Chi
authors.forename: Xing
authors.initials: X
authors.lastname: Tang
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
mesh_terms: D000975:Antioxidants / Q000737:chemistry; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry*; D005444:Flunarizine / Q000008:administration & dosage / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008055:Lipids / Q000737:chemistry; D008863:Microspheres; D013696:Temperature; D013997:Time Factors
chemical_list: D000975:Antioxidants; D002121:Calcium Channel Blockers; D005079:Excipients; D008055:Lipids; D005444:Flunarizine