Senta-Loys Zoé, Bourgeois Sandrine, Pailler-Mattei Cyril, Agusti Géraldine, Briançon Stéphanie, Fessi Hatem
Université de Lyon, Université Lyon 1, Laboratoire d'Automatique et de Génie des Procédés (LAGEP), UMR CNRS 5007, Villeurbanne, France.
Université de Lyon, Université Lyon 1, ISPB-Faculté de Pharmacie, Lyon, France.
J Pharm Pharmacol. 2017 May;69(5):582-592. doi: 10.1111/jphp.12627. Epub 2016 Sep 27.
Orodispersible films (ODF) were formulated to facilitate tetrabenazine (TBZ) administration to paediatric population for the treatment of hyperkinetic movement disorders.
ODF were obtained by solvent casting/evaporation method using four different polymers (HPMC, PVP, pullulan and HEC). Physicochemical, mechanical and biopharmaceutical characterizations as well as API state in ODF by thermal analysis were investigated to define and compare formulations. ODF stability was also monitored during 6 months to follow evolution of properties.
Analyses at T0 showed few differences between formulations: results of physicochemical and mechanical characterizations were almost similar for each formulation and TBZ appeared at the amorphous state in all cases. ODF delivery system allowed a major improvement of TBZ dissolution profile in buccal conditions compared with pure drug. However, after 3 and 6 months of stability, a TBZ recrystallization occurred for formulations based on PVP and HEC associated with a decrease of drug release in saliva conditions.
HPMC-ODF (F1) appeared as the best formulation. Indeed, physicochemical, mechanical and biopharmaceutical characteristic remained intact. In addition, TBZ remained in amorphous state during stability study.
制备口腔崩解片（ODF）以促进丁苯那嗪（TBZ）用于儿科人群，治疗运动亢进性运动障碍。
采用溶剂浇铸/蒸发法，使用四种不同的聚合物（羟丙基甲基纤维素、聚乙烯吡咯烷酮、普鲁兰多糖和羟乙基纤维素）制备ODF。研究了ODF的物理化学、机械和生物药剂学特性，以及通过热分析确定的ODF中活性药物成分（API）的状态，以定义和比较不同配方。在6个月内监测ODF的稳定性，以跟踪其性质的变化。
T0时刻的分析表明不同配方之间差异不大：每种配方的物理化学和机械特性结果几乎相似，且在所有情况下TBZ均呈无定形状态。与纯药物相比，ODF给药系统在口腔条件下显著改善了TBZ的溶出曲线。然而，在稳定性研究3个月和6个月后，基于聚乙烯吡咯烷酮和羟乙基纤维素的配方出现了TBZ重结晶现象，同时唾液条件下的药物释放减少。
羟丙基甲基纤维素-ODF（F1）似乎是最佳配方。事实上，其物理化学、机械和生物药剂学特性保持完好。此外，在稳定性研究期间，TBZ保持无定形状态。
