褪黑素口腔崩解片的研制巴洛沙星片中国健康人体药代动力学研究

【作者】 顾胜华；

【导师】 李玛琳； 徐贵丽；

【作者基本信息】 昆明医学院 ， 药理学， 2006， 硕士

【摘要】 【目的】研制褪黑素口腔崩解片，为临床提供更加方便、有效的治疗药物。 【方法】以自制吸水装置考察三种崩解剂的吸水性能；采用以正交设计优化处方；粉末直接压片法制备褪黑素口腔崩解片。以休止角及压缩度来评价粉体的流动性；考察褪黑素口腔崩解片的体内外崩解时间、硬度、含量均匀度并与褪黑素普通片进行溶出度的比较；采用恒温加速试验对褪黑素口腔崩解片进行稳定性的考察。6条Beagle犬单剂量交叉口服褪黑素口腔崩解片和普通片6mg后，用高效液相色谱法测定血浆药物浓度，用DAS软件计算药动学参数。 【结果】MCC的含量在5％～8％之间、交联PVP含量在5％～8％之间、泡腾剂的含量在5％～10％之间时，能获得较佳的吸水性；经正交设计确定三种崩解剂的含量为MCC6％、交联PVP8％、泡腾剂18％。优化后粉体的休止角θ=32.15±2.42度、压缩度C=28.45±3.17％；处方优化后的褪黑素口腔崩解片的体内、外崩解时间均在30S以内；其硬度、含量均匀度符合中国药典2005版的要求；褪黑素口腔崩解片的溶出速度明显快于褪黑素普通片；恒温加速试验3个月褪黑素口腔崩解片的外观、含量、崩解时间和溶出无变化。褪黑素口腔崩解片和普通片在Beagle犬体内的C_max分别为52.23±23.01和37.80±22.65ng·mL^-1；tmax分别为0.37±0.10和0.56±0.17h；AUC_0-6分别为45.52±32.39和43.46±29.42ng·mL^-1·h；t_1/2分别为1.05±0.76和1.13±0.52h。 【结论】褪黑素口腔崩解片体内、外崩解迅速。与褪黑素普通片相比，褪黑素口腔崩解片具有体外溶出更快，体内吸收更迅速，血药峰浓度更高的特点，并具有良好的稳定性。更多还原

【Abstract】 [Objective] : To prepare orally disintegrating tablets （ODTs） of melatonin and to provide a more convenient and effective medicine.[Method]: The hygroscopicity of disintegrants was measured by a self-made apparatus for measurement of water uptake.The prescription was optimized by means of orthogonal design and the melatonin ODTs were prepared by press the powder directly. The angle of repose and compressibility were used to investigate the flowability of powder. The disintegration time both in vivo and in vitro, hardness and uniformity of content of melatonin ODTs were examined. The dissolution rate of drug was compared with that of the conventional tablets. The stability of tablet was determined by a homoiothermic acceleration test. The plasma concentration of melatonin of 6 Beagle dogs was determined by HPLC and the pharmacokinetic parameters were caculated with drug and statistic （DAS） softerware after administered random crossover with single dose of 6mg conventional tablets or orally disintegrating tablets.[ Result ] : The evaluation of microcrystalline cellulose（MCC）, crospolyvinylpyrrolidone （PVPP ） and effervescent indicated that it can achieve good hydrophilism when the content of MCC was between 5%-8%, PVPP between 5%-8%, effervescent between 5%-10%. The optimized formulation was MCC in 6%, crospolyvinylpyrrolidone in 8%, effervescent in 18%.The powder’s angle of repose of optimal prescription was 32.15±2.42° and compressibility was 28.45±3.17%. The disintegration time both in vivo and in vitro was within 30 seconds. Either hardness or uniformity of content of melatonin ODTs was coincided with the requirement of Chinese Pharmacopoeia 2005. The dissolution of ODTs was more quickly than that of commom tablets. There are no difference of appearance, content, disintegration time and dissolution of melatonin ODTs after three month by a homoiothermic acceleration test. The C_max of the ODTs and common tablets of melatonin was更多还原