苯甲酸利扎曲普坦速溶膜剂的研制及体内外评价

Preparation and in vitro/in vivo Evaluation of Rizatriptan Benzoate Fast Dissolving Films

以拉伸性能和溶化时间为指标筛选处方，制备了以聚乙烯醇（PVA）和玉米淀粉为成膜材料的苯甲酸利扎曲普坦速溶膜剂，并进行体内外评价。采用不同方法测定溶化时间，结果均表明其体外溶化迅速，并在Beagle犬口中能在20S内完全溶化。使用桨法和漏槽式溶出仪法测定其体外溶出特性，结果均显示40～45S时的溶出率达80％以上，1min内完全溶解。鉴于膜剂的独特性质，以溶出度来评价速溶膜的溶化性能更为科学，其中漏槽式溶出仪法重现性更好、区分力更大，适合膜剂体外溶出性能的评价。Beagle犬体内药动学试验结果表明，口服自制速溶膜剂与灌胃同剂量的苯甲酸利扎曲普坦溶液具有相似的药动学性质，本品的相对生物利用度为（97．5±11．4）％。

The formulation of rizatriptan benzoate fast dissolving films was optimized with the tensile property and the disintegration time as the evaluation parameters, and the results showed that the films should be prepared with polyvinyl alcohol （PVA） and cornstarch as film-forming polymers. The in vitro/in vivo evaluation of the films was also discussed. The results of the disintegration time which were tested by different methods showed that the films could disintegrate quickly in vitro, and could disperse completely within 20 s in the oral cavity of Beagle dogs. The dissolution curves were determined by the methods of the paddle apparatus and the flow-through cell respectively, and the results showed that the dissolution of the drug was above 80 % during 40-45 s and the drug was completely released in 1 min under both conditions. Considering the special characteristics of the oral fast dissolving films, it should be more reasonable to evaluate the dissolving property by dissolution testing than disintegration time. In addition, flow-through cell method might be more reproducible and distinctive and thus was appropriate for evaluating the dissolving property of films in vitro. The results of pharmacokinetics indicated that the self-made rizatriptan benzoate fast dissolving films administered in the oral cavities and rizatriptan benzoate solution by ig administration at the same dosage to Beagle dogs exhibited similar pharmacokinetic characteristics and the relative bioavailability of the films was （97.5±11.4） %.