液体吡喹酮制剂的体外和体内味觉比较评估
Comparative in vitro and in vivo taste assessment of liquid praziquantel formulations.
作者信息
Münster Magdalena, Mohamed-Ahmed Abeer H A, Immohr Laura I, Schoch Corinna, Schmidt Carsten, Tuleu Catherine, Breitkreutz Jörg
机构信息
Merck KGaA, Pharmaceutical Technologies, Frankfurter Straße 250, 64293 Darmstadt, Germany; Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Universitätsstr. 1, 40225 Düsseldorf, Germany.
Department of Pharmaceutics, UCL School of Pharmacy, 29/39 Brunswick Square, London WC1N 1AX, United Kingdom.
出版信息
Int J Pharm. 2017 Aug 30;529(1-2):310-318. doi: 10.1016/j.ijpharm.2017.06.084. Epub 2017 Jul 8.
The taste of pharmaceuticals strongly affects the compliance of patients. This study investigated the applicability of the electronic tongue and rodent brief-access taste aversion (BATA) model for the bitter compound praziquantel (PZQ) and taste masked liquid formulations for PZQ. In a comparative study maltodextrin (MD) Kleptose linecaps 17 was selected as an alternative taste masking agent to two cyclodextrins; hydroxypropyl-beta-cyclodextrin (HP-β-CD) and sulfobutyl ether-beta-cyclodextrin (SBE-β-CD). A phase solubility study showed the highest affinity and solubilization capabilities for SBE-β-CD over HP-β-CD and MD, suggesting the highest taste masking ability for SBE-β-CD. No reliable results were achieved for PZQ with the Insent electronic tongue. Thus this system was not used for further evaluation of solutions with MD and CDs to confirm the results of the solubility study. In contrast the BATA model demonstrated conclusive responses for the aversiveness of PZQ. The concentration of PZQ inhibiting 50% of water lick numbers (called IC value) was 0.06mg/ml. In contrast to the phase solubility study, the MD enabled an equal taste masking effect in vivo in comparison to both CDs. Moreover HP-β-CD showed superior taste masking capabilities for PZQ compared to SBE-β-CD as the SBE-β-CD itself was less acceptable for the rodents than HP-β-CD. In conclusion, the BATA model was identified as a more efficient taste assessment tool for the pure PZQ and liquid formulations in contrast to the electronic tongue and the phase solubility study.
药物的味道会强烈影响患者的依从性。本研究调查了电子舌和啮齿动物短暂接触性味觉厌恶(BATA)模型对苦味化合物吡喹酮(PZQ)的适用性以及PZQ的掩味液体制剂。在一项对比研究中,选择麦芽糊精(MD)Kleptose linecaps 17作为两种环糊精(羟丙基-β-环糊精(HP-β-CD)和磺丁基醚-β-环糊精(SBE-β-CD))的替代掩味剂。相溶解度研究表明,SBE-β-CD对HP-β-CD和MD具有最高的亲和力和增溶能力,表明SBE-β-CD具有最高的掩味能力。使用Insent电子舌对PZQ未获得可靠结果。因此,该系统未用于进一步评估含有MD和环糊精的溶液以确认溶解度研究的结果。相比之下,BATA模型对PZQ的厌恶反应表现出明确的结果。抑制50%舔水次数的PZQ浓度(称为IC值)为0.06mg/ml。与相溶解度研究相反,MD在体内与两种环糊精相比具有相同的掩味效果。此外,与SBE-β-CD相比,HP-β-CD对PZQ表现出更好的掩味能力,因为SBE-β-CD本身对啮齿动物的可接受性低于HP-β-CD。总之,与电子舌和相溶解度研究相比,BATA模型被确定为一种更有效的纯PZQ和液体制剂的味觉评估工具。