Abstract

Tizanidine HCl (TH) is used as first-line therapy for the treatment of muscular spasm. The intranasal cubosomal delivery system of TH for site-specific delivery, i.e. CNS was developed. Cubosomes of TH were prepared using glyceryl monooleate (GMO) as a lipid, poloxamer 407 as stabiliser, and ethanol and polyethylene glycol 200 as co-solvent. Optimised cubosomes of TH were characterised for vesicle size, zeta potential, % drug entrapment, and mucin binding efficiency, which were found to be 50.22 nm, −6.39 mV, 69.28%, and 42.12%. It is also evaluated for CRYO-FESEM, CRYO-TEM, SAXS, residual solvent content, and in vitro drug release. Ex vivo permeation was also conducted at 7.4 and it indicates that almost 93.66% drug was diffused from a formulation in 6 h. Histopathological study of the optimised TH cubosomes suggests that the prepared formulation is non-toxic to the nasal mucosa. Pharmacokinetic and brain distribution study indicates targeted action of the formulated TH cubosomes.

摘要

盐酸替扎尼定 (TH) 用作治疗肌肉痉挛的一线疗法。开发了TH的鼻内立方体递送系统，用于定点递送，即CNS。TH 的立方体是使用单油酸甘油酯 (GMO) 作为脂质、泊洛沙姆 407 作为稳定剂、乙醇和聚乙二醇 200 作为共溶剂制备的。优化的 TH 立方体的囊泡大小、zeta 电位、药物包封率和粘蛋白结合效率进行了表征，结果分别为 50.22 nm、-6.39 mV、69.28% 和 42.12%。还对其 CRYO-FESEM、CRYO-TEM、SAXS、残留溶剂含量和体外药物释放进行评估。离体还在 7.4 下进行了渗透，表明几乎 93.66% 的药物在 6 小时内从制剂中扩散出来。优化的 TH 立体体的组织病理学研究表明，制备的制剂对鼻粘膜无毒。药代动力学和脑分布研究表明配制的 TH cubosome 具有靶向作用。