占浩慧, 黄颖聪, 马凤森. 基于微针技术的盐酸利多卡因快速局麻起效制剂的质量评价J. 药学学报, 2018,53(8): 1371-1376. doi: 10.16438/j.0513-4870.2018-0278
引用本文: 占浩慧, 黄颖聪, 马凤森. 基于微针技术的盐酸利多卡因快速局麻起效制剂的质量评价J. 药学学报, 2018,53(8): 1371-1376. doi: 10.16438/j.0513-4870.2018-0278
ZHAN Hao-hui, HUANG Ying-cong, MA Feng-sen. Quality evaluation of lidocaine hydrochloride rapid onset local anesthesia preparation based on microneedles technologyJ. Acta Pharmaceutica Sinica, 2018,53(8): 1371-1376. doi: 10.16438/j.0513-4870.2018-0278
Citation: ZHAN Hao-hui, HUANG Ying-cong, MA Feng-sen. Quality evaluation of lidocaine hydrochloride rapid onset local anesthesia preparation based on microneedles technologyJ. Acta Pharmaceutica Sinica, 2018,53(8): 1371-1376. doi: 10.16438/j.0513-4870.2018-0278

基于微针技术的盐酸利多卡因快速局麻起效制剂的质量评价

Quality evaluation of lidocaine hydrochloride rapid onset local anesthesia preparation based on microneedles technology

  • 摘要: 本文制备了基于可溶性微针的盐酸利多卡因快速局麻起效制剂,并对其进行相关质量评价。分别通过高效液相色谱(HPLC)、扫描电子显微镜(SEM)、物性分析仪、有机染色法、组织学切片、体外溶解实验和药效学实验对所制备的可溶性微针的载药量、外观形态、机械性能、皮肤刺入性能、体外溶解性能及局麻药效进行考察。结果表明,整片可溶性微针中载药量达到68.19±1.55 mg,其中针尖含有3.57±0.21 mg,微针具有良好的针型和足够的机械强度刺入皮肤,体外溶解时间为28.28±1.12 s。应用豚鼠药效模型时,可溶性微针刺入皮内1 min即可起局麻药效,远远快于复方利多卡因乳膏的100 min。其药效维持时间虽然较复方利多卡因乳膏短,但可以通过提高微针密度及制备缓控释微针来延长其药效维持时间。本文系统建立了盐酸利多卡因可溶性微针及其用于皮肤局麻的评价方法。应用盐酸利多卡因可溶性微针于皮肤局部的快速麻醉值得进一步研究。

     

    Abstract: Microneedles is an efficient, safe and novel transdermal drug delivery technology that has attracted much attention in recent decades. Microneedles could break through the skin's stratum corneum barrier and have an especially significant effect on the transdermal delivery of water-soluble small molecules and biological macromolecules. In this paper, a rapid onset local anesthetic preparation of lidocaine hydrochloride was prepared based on dissolving microneedles, and related quality evaluations were carried out. The key quality indicators of prepared lidocaine hydrochloride dissolving microneedles such as drug loading amount, appearance morphology, mechanical properties, skin penetration performance, in vitro dissolution performance and local anesthetic efficacy were investigated with HPLC, SEM, texture analyzer, organic staining, histological section, in vitro dissolution test and pharmacodynamics experiments respectively. The drug loading of the dissolving microneedles array reached 68.19 ±1.55 mg, and the needle tip contained 3.57 ±0.21 mg. The microneedles has good needle shape and sufficient mechanical strength to penetrate into the skin, which is a prerequisite for the successful administration of the preparation. The in vitro dissolution time was 28.28 ±1.12 s. When applied to guinea pig back acupuncture model which was modified by guinea pig intradermal papules model, although the efficacy maintenance time was shorter than that of compound lidocaine cream, dissolving microneedles can be activated within 1 min, which was much faster than compound lidocaine cream. It is possible to increase the duration of drug efficacy by increasing the density of microneedles and preparing microneedles for sustained and controlled release in future studies. Lidocaine hydrochloride dissolving microneedles and its evaluation methods for local anesthesia were established systematically here for the first time. The rapid effect of anesthesia with lidocaine hydrochloride dissolving microneedles on the skin was worthy of further investigation.

     

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