Preparation Of Moclobemide Ion-sensitivity Nasal In Situ Gel

Objective:To preparate and evaluate moclobemide ion-se-nsitivity nasal in situ gels.Methods:(1)The HPLC method was established to determine the moclobemide content.(2)Single factor tests were used to choose the dosage of pharmaceutical base and the kind of solubilizer by investigating the state of the preparation and the viscosity of gel before and after in situ gel acting with artificial nasal fluid.(3)Taking clarity of the solution and in vitro cumulative release as the indexes,orthogonal design was used to investigate the optimized dosage of mixed solubilizer.(4)Investigations in vitro properties of moclobemide ion-sensitivity nasal in situ gel and ciliary toxieity were taken,including phase transition cation intensity,gelling properties.(5)In vitro cumulative release rate and cumulative corrosion rate were investigated to explore the drug release mechanism of moclobemide ion-sensitivity nasal in situ gel.(6)The preliminary quality standard of the preparation was presented.Results:(1)The HPLC method established is sensitive,precise and rapid,and can be used in measurement of concentration of moclobemide.(2)The deacetylated gellan gum(0.1%)was decided as the dosage of pharmaceutical base,and 1,2-propanediol,Tween-80 and PEG 400 were decided as solubilizer by single factor test.(3)The best prescription was found to be 0.1%of the deacetylated gellan gum,20%of 1,2-propanediol,10%of PEG 400,4%of Tween-80,of 0.01%thimerosal by the orthogonal test.(4)Four seconds after acting with artificial nasal fluid,the in situ gel was gelatinize.The phase transition cation intensity was:Na+:87 mmol/L,K+:25 mmol/L and Ca2+:5 mmol/L(about half of cation intensity of artificial nasal fluid).Four hours after taking medicine,the ciliary mucosal surface was intact,and the cilia was numerous and active.(5)In vitro cumulative release test showed that the sustained release of drug was about four hours.The mathematical model of drug release could be described by Higuchi equation(r=0.9922).The cumulative corrosion rate of in situ gel was less than 5%within four hours.The linear relationship between cumulative release rate and cumulative corrosion rate was not significant(r=0.933),which indicated that the drug release mechanism was a diffusion type rather than a corrosion type.(6)The moclobemide ion-sensitivity nasal in situ gel can be controlled effectually by the quality standard established.Conclusion:The quality of the moclobemide ion-sensitivity nasal in situ gel was stable and controlled.It is suitable for nasal administration.