Thouvenin Agathe, Toussaint Balthazar, Marinovic Jelena, Gilles Anne-Laure, Dufaÿ Wojcicki Amélie, Boudy Vincent
CNRS, Inserm, UTCBS, Université Paris Cité, F-75006 Paris, France.
Département Recherche et Développement Pharmaceutique, Agence Générale des Équipements et Produits de Santé (AGEPS), AP-HP, F-75005 Paris, France.
Pharmaceutics. 2022 Sep 24;14(10):2039. doi: 10.3390/pharmaceutics14102039.
()-ketamine presents potential for the management of acute pain and, more specifically, for the prevention of pain associated with care. However, the administration route can be a source of pain and distress. In this context, a smart formulation of ()-ketamine was designed for buccal administration. The combination of poloxamer 407 and sodium alginate enables increased contact with mucosa components (mucins) to improve the absorption of ()-ketamine. In this study, rheological studies allowed us to define the concentration of P407 to obtain a gelling temperature around 32 °C. Mucoadhesion tests by the synergism method were carried out to determine the most suitable alginate among three grades and its quantity to optimize its mucoadhesive properties. Protanal LF 10/60 was found to be the most effective in achieving interaction with mucins in simulated saliva fluid. P407 and alginate concentrations were set to 16% and 0.1%. Then, the impact of P407 batches was also studied and significant batch-to-batch variability in rheological properties was observed. However, in vitro drug release studies demonstrated that this variability has no significant impact on the drug release profile. This optimized formulation has fast release, which provides potential clinical interest, particularly in emergencies.
（）-氯胺酮在急性疼痛管理方面，尤其是在预防与护理相关的疼痛方面具有潜力。然而，给药途径可能会引起疼痛和不适。在此背景下，设计了一种用于颊部给药的（）-氯胺酮智能制剂。泊洛沙姆407和海藻酸钠的组合能够增加与黏膜成分（黏蛋白）的接触，从而提高（）-氯胺酮的吸收。在本研究中，流变学研究使我们能够确定泊洛沙姆407的浓度，以获得约32℃的胶凝温度。通过协同作用法进行了黏膜黏附试验，以确定三种等级中最合适的海藻酸盐及其用量，以优化其黏膜黏附性能。发现Protanal LF 10/60在模拟唾液中与黏蛋白相互作用方面最有效。泊洛沙姆407和海藻酸盐的浓度分别设定为16%和0.1%。然后，还研究了泊洛沙姆407批次的影响，观察到流变学性质存在显著的批次间差异。然而，体外药物释放研究表明，这种差异对药物释放曲线没有显著影响。这种优化后的制剂具有快速释放的特性，具有潜在的临床应用价值，尤其是在紧急情况下。
