Studies On The Antidepressant Effect Of Ifenprodil Tartrate And Preparation Of Ifenprodil Tartrate Nasal In Situ Gel

Objective:1.Antidepressant effect of ifenprodil tartrate was explored andevaluated.2. Ifenprodil tartrate nasal in situ gel was prepared. Methods:1.Forced swimming test and learned helplessness test were selected to evaluaterapid antidepressant effect of ifenprodil tartrate by observing behavior ofexperimental mice.2. The HPLC method was established to determine theifenprodil tartrate content.3. Screening tests were applied to select the dosageof1,2-propylene glycol being as a solubilizer in the prescription of ifenprodiltartrate ion-sensitivity nasal in situ gel.4. Dacetylated gellan gum(DGG) wasused as pharmaceutical base. Concentration ratio of DGG was investigated onthe basis of index properties including in situ gel forming, gelling time,viscosity, cumulative release rate and phase transition cation intensity.5. Threebatches of in situ gel samples were prepared according to the optimizedprescription, which were used to verify the prescription. Results:1. Thecumulative immobility time of the group of mice those were given1mg/kg,2mg/kg or3mg/kg ifenprodil tartrate was respectively shorten evidently inforced swimming test(P﹤0.05) comparing with the negative control group at each half an hour, two hours and four hours after administration, and there is nosignificant difference effect between two doses（P﹥0.05）. The decrease ofcumulative immobility time of the group of mice was not respectively observedat six hours after administratio（nP﹥0.05）.2. The number of escape failed timesof the group of mice those were given1mg/kg or3mg/kg ifenprodil tartratedecreased evidently in shuttle box test(P﹤0.05) comparing with the modelcontrol group at each half an hour, two hours and four hours afteradministration, and there is no significant difference in the effect of two doses（P﹥0.05）.3. The best solubilizer was14%of1,2-propylene glycol.4. Thebest concentration of dacetylated gellan gum is0.4%in preparation of the insitu gel. The in situ gel prepared is clear liquid. The gelling time of it is about5s. The viscosity is approximate5Pa s. The cumulative release rate is about65%at4hours. The phase transition cation intensity is: Na+:50mmol/L, K+:15mmol/L, Ca2+:1.4mmol/L, which is less than half intensity of the nasal fluid.All the properties are able to meet the demand of intranasal administration.5.Three batches of in situ gel samples were assayed to verify the prescription andthe preparation. The gelling time is5.1s,5.4s and5.6s respectively. Theviscosity is5.1Pa s,5.2Pa s,5.2Pa s respectively. The phase transition cationintensity is the same: Na+:50mmol/L, K+:15mmol/L, and Ca2+:1.4mmol/L.The cumulative release rate is63.09%,65.56%and63.44%respectively at4hours. Conclusion:1. The results of the tests on animal models of depressionshow the rapid antidepressant effect of ifenprodil tartrate which is last at4 hours, but the effect is not positive correlate with dosage.2. The HPLC methodestablished is simple, reproducible and specific for assaying the ifenprodiltartrate.3. The ifenprodil tartrate ion-sensitivity nasal in situ gel developed inthis process is stable and controlled. It is suitable for nasal administration.