Formulation, stability and degradation kinetics of intravenous cinnarizine lipid emulsion.
Cinnarizine was loaded in the lipid emulsion to develop an intravenous formulation with good physical and chemical stability. High-pressure homogenization was used to prepare the lipid emulsion. The factors influencing the stability of cinnarizine lipid emulsion, such as different drug loading methods, pH, temperature, sterilization methods and sterilization time were monitored by high-performance liquid chromatograph. The degradation of cinnarizine in aqueous solution and lipid emulsion both followed apparent first-order kinetics. A possible degradation mechanism was postulated by the bell-shaped pH-rate profile of cinnarizine. Localization of the drug in the interfacial lecithin layer significantly improved the chemical stability of cinnarizine and its stabilizing mechanism was thoroughly discussed and proved. The activation energy of cinnarizine in lipid emulsion was calculated to be 51.27 kJ/mol which was similar to that in aqueous solution. This indicates that the stabilizing effect of the drug carrier on cinnarizine was not an alteration of the degradation reaction. In addition, shelf-life of cinnarizine in lipid emulsion was estimated to be 1471.6 days at 4 degrees C, which is much longer compared with 19.8 days in aqueous solution. The final products were stable enough to resist a 121 degrees C rotating steam sterilization for 15 min.
Shi
Shuai
S
Department of Pharmaceutics, Shen yang Pharmaceutical University, Wenhua Road 103, Shen yang 110016, Liaoning Province, PR China.
Chen
Hao
H
Cui
Yue
Y
Tang
Xing
X
D000465:Algorithms; D002021:Buffers; D002626:Chemistry, Pharmaceutical; D002936:Cinnarizine / Q000737:chemistry*; D004355:Drug Stability; D004356:Drug Storage / Q000379:methods; D045703:Emulsifying Agents / Q000737:chemistry; D004655:Emulsions / Q000138:chemical synthesis / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D007700:Kinetics; D008055:Lipids / Q000737:chemistry*; D010316:Particle Size; D011312:Pressure; D013242:Sterilization / Q000379:methods; D013696:Temperature; D014280:Triglycerides / Q000737:chemistry; D014867:Water / Q000737:chemistry
D002021:Buffers; D045703:Emulsifying Agents; D004655:Emulsions; D008055:Lipids; D014280:Triglycerides; D014867:Water; D002936:Cinnarizine