| The orally disintegrating tablet (ODT), which is expected to dissolve or disintegrate in the buccal cavity without drinking water or with small amount of water. ODT has short dinsintegration time and rapid dissolution. It is swallowed easily and convenient for administration. Pyridostigmine bromide was used to prepare ODT, and four sections were involved in our study.The first section was preparation of taste-masking pyridostigmine bromide solid dispersion by solvent evaporation-deposition method and identified by infrared spectra (IR) and differential scanning calorimetry (DSC). Comprehensive score of the optimum solid dispersion was 92.4. IR and DSC showed the presence of pyridostigmine bromide in carriers maybe in the form of amorphous. The optimum solid dispersion can mask the bitter taste of pyridostigmine bromide significantly in the buccal cavity. Stability of solid dispersion was affected by temperature, humidity and illumination. The second section was preparation of ODT by direct compression. Determination of disintegration time of ODT in vitro was established. Single factor design and central composite design-response surface methodology were used to optimize the content of diluents, disintegrants and flavoring agent. ODTs prepared by optimized formulations were integrity with desirable taste as well as shortest wetting time and disintegration time.The third section was quality control of ODT. Preliminary stability of ODT was investigated by impact factors, accelerated and long-term test. The relative standard deviation of weight, hardness, disintegration time and relative content of ODT were in according with Chinese Pharmacopeia. The ODT should be stored in low temperature, moistureproof and dark. There were no significant difference in disintegration time and relative content when stored in room temperature.The forth section was study on pharmacokinetics and equivalent of ODT and commercial tablets in rabbits. The concentration of pyridostigmine bromide in plasma was determined by reversed phase ion- pair chromatography. The method was found to be linear over the examined concentration range of 0.02～2.00 mg·L-1 with the LLOQ of 0.015 mg·L-1. The extraction recovery was more than 82% with good precision and accuracy. The method could be used to determine the pyridostigmine bromide in plasma. ODT and commercial tablets were fitted to the one compartment opened model. The pharmacokinetic parameters of ODT and commercial tablets in rabbit plasma were as follows: Cmax (1.81±0.09)mg·L-1 and (1.71±0.03) mg·L-1, Tmax (2.25±0.27) h and (2.67± 0.26) h; AUC0-24(15.77±0.54) mg·h·L-1 and(14.85±0.17)mg·h·L-1, AUC0-∞ (16.06±0.63) mg·h·L-1 and (15.14±0.19)mg·h·L-1. The main pharmacokinetic parameters analyzed by variance, two side t-test and wilcoxon rank sum test, ODT and commercial tablets were bioequivalent in vivo. |
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