Praparation Of Dimenhydrinate Orally Disintegrating Tablets

Dimenhydrinate(DMH) was widely used as a kind of histamine antagonist in clinic. It had positive curative effects and low side effects. In order to facilitate motion sickness sufferers to swallow the drug, we studied and prepared DMH orally disintegrating tablets with good taste.In the study, physical and chemical properties of DMH such as equilibrium solubility, stability of aqueous solution and apparent oil-water partition coefficient were investigated.Various ratios of DMH to Eudragit E100 were used to prepare taste masking solid dispersion of the drug by solvent method and differential scanning calorimeter(DSC) was applied to analyse the solid dispersion. DSC analysis verified that in the solid dispersion the drug existed as a amorphic state. In the stress' testing, experiments showed that in high temperature, in high humidity and in strong light the solid dispersion was stable.The water uptake kinetics of several kinds of excipients usually used for orally disintegrating tablets was investigated. The results suggested that the ability of soluble excipients such as mannitol and lactose was weak, while the water uptake rate of microstalline cellulose(MCC) was the fastest and the water uptake amount of croscarmellose sodium(CCMC-Na) and sodium carboxymethyl starch was the highest. Then the tablets were prepared by powder direct compression. Orthogonal design was carried out to optimize the formulation. The result showed that the weight of the tablet was the significant factor and the higher weight of tablet was associated with shorter time of disintegration of the tablet. The final tablet was mainly composed of 35.6%mannitol,10%MCC and 10%CCMC-Na respectively with disintegrating time of about 20 seconds in vitro and the tablet weight was 300mgTo determine the taste threshold and the dissolution rate of the drug in the simulated saliva ,a dissolution pool was designed. The results suggested the taste threshold of DMH was 125-750μg·mL^-1 and the maximum concentrations of DMH in the dissolution solution of tablets with unmasked drug and with taste-masked drug were 2.46μg·mL^-1 and 0.213μg·mL^-1 respectively. It was also found that higher concentration of DMH in the dissolution solution...