Paavola A, Yliruusi J, Kajimoto Y, Kalso E, Wahlström T, Rosenberg P
Department of Pharmacy, University of Helsinki, Finland.
Pharm Res. 1995 Dec;12(12):1997-2002. doi: 10.1023/a:1016264527738.
Methods of delaying the action of local anesthetics are important, since short duration of action limits their use in the treatment of postoperative and chronic pain. The present study evaluated the use of low-viscosity gels in prolonging the release of lidocaine.
Release of lidocaine from 2% lidocaine.HCl containing methylcellulose (MC), hydroxypropylmethylcellulose (HPMC), sodiumcarboxymethyl cellulose (CMC), and poloxamer 407 (PO) gels was studied in phosphate buffer, pH 7.4, at 37 degrees C. Commercial metylcellulose gel (MCcom) served as control. The in vivo efficacy of the respective gel formulations were evaluated in rats. The gel was injected into the vicinity of the sciatic nerve and nociception and motor function were tested.
The cumulative amount of lidocaine released during 8 hr was slowest from the PO gel, followed by the CMC, HPMC and MC gels. The antinociceptive effect was not prevented by the motor block and lasted longest with the PO gel. Good linear and rank order correlation was obtained between in vitro and in vivo results. The microscopic examination of the tissue samples revealed only mild or no irritation of the skeletal muscle tissue by the PO, HPMC, and CMC gels.
Based on these results poloxamer gel proved to be the most promising carrier for lidocaine.
延缓局部麻醉药作用的方法很重要，因为作用时间短限制了它们在术后疼痛和慢性疼痛治疗中的应用。本研究评估了低粘度凝胶在延长利多卡因释放方面的应用。
在37℃、pH 7.4的磷酸盐缓冲液中研究了利多卡因从含甲基纤维素（MC）、羟丙基甲基纤维素（HPMC）、羧甲基纤维素钠（CMC）和泊洛沙姆407（PO）凝胶的2%盐酸利多卡因中的释放情况。市售甲基纤维素凝胶（MCcom）作为对照。在大鼠中评估了各凝胶制剂的体内疗效。将凝胶注射到坐骨神经附近，并测试痛觉和运动功能。
8小时内利多卡因的累积释放量从PO凝胶中释放最慢，其次是CMC、HPMC和MC凝胶。运动阻滞并未阻止镇痛作用，且PO凝胶的镇痛作用持续时间最长。体外和体内结果之间获得了良好的线性和等级相关性。组织样本的显微镜检查显示，PO、HPMC和CMC凝胶对骨骼肌组织仅有轻度刺激或无刺激。
基于这些结果，泊洛沙姆凝胶被证明是利多卡因最有前景的载体。
