Study On The Preparation Of Dexketoprofen Trometamol Temperature Sensitive Hydrogels

Objective By the study of the preparation of Dexketoprofen tromethamine temperature-sensitive hydrogel,in vivo release characteristics,quality standards,stability,tissue compatibility and pharmacokinetic study,developed a new generation of non-steroidal anti-inflammatory drugs with excellent anti-inflammatory and analgesic effects.Methods To establish the UV spectrophotometry analysis method for preformulation study of dexketoprofen trometamo.Used the gelation time to evaluate the performance of hydrogel study.On the basis of single factor experiments,used cumulative release as index,screened out the best prescription composition of thermo-sensitive hydrogel.Preparation batches of Dexketoprofen tromethamine temperature-sensitive hydrogel,examine its process reproducibility and stability.Made in vitro comparative experiments of Dexketoprofen tablets and thermo-sensitive hydrogel and investigate the release mechanism.Used UPLC-MS/MS method to studied the in vivo pharmacokinetics conducted in rats of injection of homemade Dexketoprofen tromethamine temperature-sensitive hydrogel,homemade Dexketoprofen tromethamine solution and dexketoprofen trometamol tablet.Used the Loo-Rigelman method to calculate the in vivo absorption rate in different time,and studied linear regression fitting between in-vivo release and in-vitro accumulative release,and evaluated in-vitro and in-vivo correlation.The tissue compatibility experimental was used to explore the feasibility of injectable formulation.Results Through orthogonal experiments,the hydrogel prescription:the drug solution concentration of 0.25 g/mL,CS amount of 0.04 g,β-GP/CS solution ratio of 0.5.The results showed that the thermo-sensitive hydrogel release behavior was fit to the synergismof diffusion and bulk erosio.TStability studies indicated that thermo-sensitive hydrogel’ was stable at humidity and low-temperature and the reproducibility of the process were good.The comparative experiments of the temperature-sensitive hydrogel and dexketoprofen enteric-coated tablets showed that hydrogel had the obvious effect of sustained-release.Pharmacokinetic results showed that:the hydrogel are extravascular two compartment model in vivo process.Compared with the injection of dexketoprofen trometamol thermo-sensitive hydrogel and dexketoprofen trometamol solution.It was showed that the Cmax of hydrogel was significantly lower and the Tmax has been extended,so the hydrogel had a clear sustained release characteristics.Compared with the injection of dexketoprofen tromethamine thermo-sensitive hydrogel and dexketoprofen tromethamine.It was showed that it improved the bioavailability of dexketoprofen trometamol.Calculated with the Loo-Rigelman method,the in-vitro and in-vivo correlation of Dexketoprofen tromethamine temperature-sensitive hydrogels was significant,r = 0.9625,showed a good in-vitro and in-vivo correlation.The tissue compatibility experimental results showed that the thermo-sensitive hydrogel had a good tissue compatibility and meet the safety standards of biological materials.Conclusion The developed Dexketoprofen tromethamine temperature-sensitive hydrogel had a simple and stable prescription,both in vivo and in vitro experiments show that the sustained-release formulation had good features and good histocompatibility.It has made a basis for the research of Dexketoprofen tromethamine sustained-release formulations.