The Preparation Of Orally Disintegrating Tablets Of Dimenhydrinate

[Objective] To prepare dimenhydrinate orally disintegrating tablets (ODTs) in order to provide a more convenient, safer and more effective medicine for clinical use.[Methods] The grains which contain dimenhydrinate and Eudragit E100 were prepared by a solvent way, and Eudragit E100 was used as bitter-masking aid which could mask the bitterness of the dimenhydrinate. The ratio of Eudragit E100 to dimenhydrinate was investigated. The result of bitter masking was determined by oral-test method by volunteers. The hygroscopicity of three disintegrants was measured by a self-made apparatus for measurement of water uptake. Effervescent was evaluated carefully including its influence on the disintegrating time of blank tablets in vitro and in vivo. On the basis of the preliminary prescription, the formulation was optimized by central composite design and response surface methodology using disintegrating time as evaluation index. The angle of repose and compressibility were used to investigate the flowability of powder. Dimenhydrinate ODTs were prepared by pressing the powder directly. The disintegration time both in vivo and in vitro, hardness and uniformity of content of dimenhydrinate ODTs were examined. The dissolution rate of drug was compared with that of the conventional tablets. The in vivo behavior of the tablets was evaluated in Rhesus after administration of orally disintegrating tablets and ordinary tablets in the market. Pharmacokinetic parameters of the two formulations were compared, and the relative bioavailability was calculated.[Results] The ratio of dimenhydrinate to Eudragit E100 with 2 to 1 could mask the bitter taste. The evaluation of MCC,PVPP and effervescent indicated that it could achieve good hydrophilism when the content of MCC was between 5%～8%, PVPP between 5%～13%, effervescent between 5%～10%. The optimized formulation was MCC in 5.3%, PVPP in 8.1%, and effervescent in 15.6%. The powder's angle of repose of optimal prescription was 32.52±1.19°and compressibility was 27.83±0.80 %. The disintegrating time both in vivo and in vitro were within 1min. Either hardness or uniformity of content of dimenhydrinateODTs was coincided with the requirement of Chinese Pharmacopoeia 2005, and had a faster dissolving speed compared with ordinary tablets (P<0.05 ) .The dissolution of ODTs was quicker than that of commom tablets. The C_max of the ODTs and common tablets of dimenhydrinate was 0.325±0.181 and 0.159±0.105μg·mL^-1 respectively; the AUC_0-12hwas 1.112±0.432 and 0.732±0.262μg·mL^-1·h respectively. The relative bioavailability of dimenhydrinate ODTs was 153.82±41.62%. The C_max,AUC_0-12h between the ODTs and common tablets had significant difference (P<0.05) , which showed that the absorption extent of dimenhydrinate ODTs was better than common tablets. The T_max was 1.875±0.666 and 2.583±0.736h respectively, but there had no significant difference (P>0.05) .[Conclusion] The orally disintegrating tablets of dimenhydrinate which are prepared in this dissertation have these advantages: tasting pleasant, disintegrating rapidly, and the dissolution speed is improved remarkably. Compared with the common tablets, the dimenhydrinate orally disintegrating tablets showed quicker dissolution in vitro .