Study On Nitroglycerin Orally Disintegrating Tablets

Objective:Nitroglycerin is a commonly used antianginal agent. The aim of the present study was to prepare nitroglycerin oral disintegrating tablets and investigate its quality and stability.Method:At first single factor experiments were carried out in order to choose disintegrant, binder, the proportion of MCC and L-HPC, lubricant, particle size, and to study effect of hardness upon disintegration time. Several methods to determine disintegration time were compared. On this basis, Central composite design was used to optimize the formulation of orally disintegrating tablets, the response of the experiment included:disintegration time/hardness, wetting time, water uptake time, quantity of water uptake, disintegration time in vivo, taste and overall desirability. Meanwhile, the Correlation between disintegration time in vivo and in vitro was investigated. Orally disintegrating tablets were produced according to the optimized formulation.Quality Evaluation of orally disintegrating tablets had been finished, including appearance, tablets weight variation, disintegration time limit, content(and content uniformity), dissolution, related substance.Stress testing, accelerated testing and long-term testing were carried out according to Guidance for Stability Testing of New drug substance and products.Results:According to the single factor experiments, the condition was determined, that PVPP is disintegrant, binder is3%PVPk30, the proportion of MCC and L-HPC is8:2, lubricant is magnesium stearate, the particle was passed24mesh sieve. The optimum of multi-nonlinear equation is: OD2=-2.01925+0.1418902X1,-0.0129976X,-0.0686964X3-0.00193716X12+0.00120318X32+0.00100021X1,X3(r2=0.836) The optimum scale of three factors are:MCC:35%～45%; PVPP:4～6%; Xylitol:15%-20%. Correlation between disintegration time in vivo and in vitro using different methods is good(P<0.05).Disintegration time limit was determined using both static method and appartus method. The content of nitroglycerin was measured by HPLC method on C18column with a mixture of methanol:water:acetonitrile (52:43:5) as mobile phase at a flow rate of0.7ml/min under the wavelength of215nm. The related substances in nitroglycerin orally disintegrating tablets could be detected by TLC method. To develop the chromatograms in the solvent system consisting of a mixture of toluene and ethyl acetate (4:1) and spray the plate with a1in100solution of diphenylamine in methanol. Water was used as dissolution medium and apparatus was operated with rotation rate of75r·min-1. The dissolution of3min should be not less than80%. And the hardness of tablets is more than2Kg.The results of stress testing showed that orally-disintegrating tablets were unstable to high humidity(75%±1%,90%±5%), during disposition, Nitroglycerin was easy to volatilize. Result of accelerated testing and long-term testing showed that tablets are stable during disposition.Conclusion:The prepared tablets were complied with the character of orally disintegrating tablets, and it has pleasant stability. The method is convenient, stable and reliable for the quality control in nitroglycerin orally disintegrating tablets. Tablets are unstable to humidity and heat, its package should protect against moisture.