Studies On Orally Disintegrating Tablets Of Taste Masked Phencynonate HC1by Drug-ion Exchange Resin Complex

Phencynonate HCl is a central anticholinergic agent. It has been developed as a new medicine for motion sickness. The only conventional tablet is the commercially available preparation currently. In order to improve patient compliances and preparation of orally disintegrating tablet containing ion exchange resin-drug complex was introduced in the article, we selected phencynonate HCl as model drug and cationic exchange resin (Amberlite(?) IRP88) as carrier.Some physicochemical properties such as solubility, pKa,logP were studied in this article. The cationic ion exchange resin (Amberlite(?) IRP88) is preferable to be used in the preparation of the drug-resin complexes due to the tertiary amine moieties in the drug molecule.In order to get higher drug availability and drug loading, the factors such as drug concentration, amount of resin, temperature and pH value of the solutions were studied. Finally, the method was optimized with drug concentration of1.0mg/mL, the ratio of drug-resin was1:2(wt/wt), the operation temperature was room temperature (25’C), using deionized water as medium. Analysis of PXRD and DSC indicates that the drug was changed from the crystal structure to the amorphous form due to the resins presented as a carrier. So, the drug is combined with the resin by the ion bond in cationic exchange resin rather than the simple physical absorption. Effecting factors on drug-resin complexes had been studied which showed the release rate mainly depend on H+strength, temperature and species of exchangeable ions in the medium. The release rate of drugs increases with the increasing strength of H+and temperature. Exchange capacity of exchangeable ions is H+>Na+>K+>Ca2+, showing the molecular weight increases with the decreasing exchange capacity. The release of phencynonate from the drug-resin complexes were controlled by a particle diffusion process.Direct compression is the commonly used method to prepare orally disintegrating tablet. D-Mannitol and mannitol-starch mixture at the optimal ratio of1:1(mg/mg) was chosen as the bulking agent. It shows that orally disintegrating tablet containing20%PVPP has the shortest wetting time and disintegration time in experiments on the wetting time, in vitro and in vivo disintegration time with three superdisintegrants: CMS-Na, PVPP, CCMC-Na. Finally,20%PVPP was chosen as the final prescription. The dissolution test results of orally disintegrating tablets and commercial tablets in four mediumsindicated that the dissolution rate of orally disintegrating tablet containing ion exchange resin-drugcomplex was greatly enhanced compared with the commercial tablets in pH1.0and pH4,5medium.However, no release of the drug occurred from the orally disintegrating tablet in deionized water and thereis little release in the artificial saliva. These results indicate that orally disintegrating tablet can be quicklyreleased in an acid environment similar to the human stomach and it can be slightly release in the oralcavity, thereby making the taste masking effect.The effect of taste masking and sandness feel were evaluated through a single blind study in humanvolunteers. It was found that orally disintegrating tablet containing ion exchange resin-drug complex canmask bitter taste perfectly and avoid sadness feeling.