利培酮口溶膜的制备及体内外评价

Preparation and in vitro/in vivo Evaluation of Risperidone Orodispersible Films

首先测定了国外市售利培酮口溶膜和国内市售口崩片在不同溶出介质中的溶出曲线,结果在水中具有较大的区分力,因而用水作为溶出介质测定溶出曲线并结合溶化时间和物理性能进行处方筛选,制备了利培酮口溶膜。结果表明,自制口溶膜在4种不同pH值的溶出介质中1 min均溶出80%以上,2 min内溶出完全,与国外市售口溶膜的体外溶出行为基本一致。差示扫描量热(DSC)和X射线衍射(XRD)研究结果显示,利培酮以无定形态分散于载体材料中。Beagle犬体内药动学试验结果表明,自制口溶膜与国外市售口溶膜具有相似的药代动力学行为;自制口溶膜的相对生物利用度以利培酮计为(109.1±9.5)%、以活性代谢物9-羟基利培酮计为(102.0±17.3)%。

The dissolution profiles of the risperidone orodispersible films in foreign market and orally disintegrating tablets in domestic market in different media were investigated, and water was considered as discriminative according to the results of above tests. Then the formulation of risperidone orodispersible films was optimized with the dissolution profiles in water, together with the disintegration time and the mechanical properties as the evaluation parameters. The results showed that the dissolution of risperidone from the self-made orodispersible films was above 80 % within 1 min in four dissolution media with different pH values and risperidone was completely dissolved within 2 min. The dissolution behaviors of the self-made risperidone orodispersible films were similar to those of the marketed orodispersible films. The resuks of differential scanning calorimetry （DSC） and X-ray diffraction （XRD） demonstrated that risperidone existed in an amorphous state in the carriers. The results of pharmacokinetics in Beagle dogs indicated that the self-made and the marketed orodispersible films exhibited similar pharmacokinetic characteristics. The relative bioavailabilities of self-made films were （109.1±9.5） % based on risperidone and （102.0±17.3） % based on 9-hydroxyrisperidone, the active metabolite.