Hu Kai-Li, Mei Ni, Feng Liang, Jiang Xin-Guo
Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, People's Republic of China.
Arzneimittelforschung. 2009;59(11):543-9. doi: 10.1055/s-0031-1296442.
Intranasal lidocaine hydrochloride (LID, CAS 73-78-9) has been shown useful in the control of a series of symptoms such as migraine, cluster headache and trigeminal neuralgia in clinical studies. However, rapid nasal mucociliary clearance of intranasal solution usually affects its efficiency. In this study, a nasal gel formulation was designed using hydroxypropyl methyl cellulose (HPMC) as mucoadhesive polymer to increase the residence time of LID on the nasal mucosa. Based on the results of a preliminary single factor study, the gel formulation was optimized by central composite design to provide better drug release and bioadhesive intensity. The methods for investigating the gel's bioadhesive intensity and for spectrophotometric determination of LID were established. Then the parameters for the LID in vitro release study such as release medium, release apparatus and rotation rate were decided upon a method of f2 fit factor. The in vitro drug release property of the optimized formulation was proved to comply with the Higuchi equation.
鼻内用盐酸利多卡因(LID,化学物质登记号73 - 78 - 9)在临床研究中已被证明可有效控制一系列症状,如偏头痛、丛集性头痛和三叉神经痛。然而,鼻内溶液在鼻腔内的快速黏液纤毛清除通常会影响其疗效。在本研究中,设计了一种以羟丙基甲基纤维素(HPMC)作为黏附聚合物的鼻用凝胶制剂,以延长利多卡因在鼻黏膜上的停留时间。基于初步单因素研究的结果,采用中心复合设计对凝胶制剂进行优化,以实现更好的药物释放和生物黏附强度。建立了研究凝胶生物黏附强度以及分光光度法测定利多卡因的方法。然后,依据f2拟合因子法确定了利多卡因体外释放研究的参数,如释放介质、释放装置和转速。结果表明,优化制剂的体外药物释放特性符合 Higuchi 方程。