盐酸替扎尼定微乳凝胶的优化。

Optimization of Microemulgel for Tizanidine Hydrochloride.

机构信息

Department of Pharmaceutics, School of Pharmacy, Dr. Vishwanath Karad MIT World Peace University, Survey No. 124, MIT College Campus, Paud Rd, Kothrud, Pune, Maharashtra 411038, India.

出版信息

Antiinflamm Antiallergy Agents Med Chem. 2020;19(2):158-179. doi: 10.2174/1871523018666190308123100.

DOI:10.2174/1871523018666190308123100

PMID:30854978

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7475941/

Abstract

BACKGROUND

Tizanidine hydrochloride acts centrally as a muscle relaxant. It is used for the treatment of painful muscle spasm, spasticity associated with multiple sclerosis or spinal cord injury and treatment of muscle spasticity in spinal cord disease. Tizanidine hydrochloride belongs to BCS class II. It has low oral bioavailability and short halflife. Incorporating this drug in microemulgel is an excellent way to overcome problems associated with the drug.

OBJECTIVES

Present research work was aimed to develop and optimize a microemulsion based gel system for tizanidine hydrochloride.

METHODS

Screening of oil, surfactant and co-surfactant was carried out. Ternary phase diagram was constructed to obtain concentration range of components. The prepared microemulsion was evaluated for pH, globule size, zeta potential, conductivity, density and viscosity. 32 level factorial design was applied to study the effect of concentration of carbopol 934 and HPMC K15M on % cumulative drug release and viscosity of microemulgel using software Design Expert. Microemulgel was evaluated for pH, spreadability, viscosity, syneresis, drug content, bioadhesive strength, in-vitro as well as ex-vivo diffusion study.

RESULTS

Microemulsion was prepared by using isopropyl myristate as oil, tween 80 as a surfactant and transcutol P as cosurfactant. Largest transparent microemulsion region was found with Smix ratio of 1:1. FE-SEM showed globule size 28μm for batch B1 and zeta potential was -1.27mV indicating good stability of the microemulsion. Optimised batch was F6 which showed 92% drug release within 8 hours. It followed the Korsmeyer-Peppas model.

CONCLUSION

A stable, effective and elegant microemulgel formulation, exhibiting good in-vitro and ex-vivo drug release was formulated.

摘要

背景

盐酸替扎尼定通过中枢作用起到肌肉松弛剂的效果。它被用于治疗疼痛性肌肉痉挛、多发性硬化症或脊髓损伤相关的痉挛以及治疗脊髓疾病中的肌肉痉挛。盐酸替扎尼定属于 BCS 分类 II 类药物，其口服生物利用度低，半衰期短。将该药物制成微乳凝胶是克服与药物相关问题的绝佳方法。

目的

本研究工作旨在开发和优化盐酸替扎尼定的微乳凝胶系统。

方法

对油相、表面活性剂和助表面活性剂进行了筛选。构建了三元相图以获得各成分的浓度范围。对制备的微乳进行 pH 值、粒径、zeta 电位、电导率、密度和黏度的评价。采用 32 水平析因设计，应用软件 Design Expert 研究 Carbopol 934 和 HPMC K15M 的浓度对微乳凝胶的 %累积药物释放和黏度的影响。对微乳凝胶进行 pH 值、铺展性、黏度、离浆性、药物含量、生物黏附强度、体外和体内扩散研究。

结果

以肉豆蔻酸异丙酯为油相，吐温 80 为表面活性剂，丙二醇为助表面活性剂制备微乳。Smix 比为 1:1 时发现最大透明微乳区。FE-SEM 显示批 B1 的粒径为 28μm，zeta 电位为-1.27mV，表明微乳的稳定性良好。优化后的批次为 F6，8 小时内药物释放达到 92%。它遵循 Korsmeyer-Peppas 模型。