Intranasal spray of cubosomal tizanidine hydrochloride for brain targeting: in vitro and in vivo characterisation

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.

Keywords:

• Tizanidine HCl
• cubosomes
• brain targeting
• intranasal delivery
• blood–brain barrier
• muscular spasm

Acknowledgements

We are thankful to AICTE (All India Council of Technical Education) for providing scholarship during the project work. We are also thankful to Symed Laboratories, Hyderabad, India and Gattefosse, USA for providing gift sample of TH and glyceryl monooleate.

Author contributions

Dr. Hetal Thakkar: conceptualisation, supervision, writing-review and editing, and investigation. Bhumi Modi: conceptualisation, methodology, data curation, visualisation, investigation, validation, and software. Brijesh Patel: conceptualisation, writing – original draft preparation, software, writing – reviewing and editing, and investigation.

Disclosure statement

The authors hereby declare that they do not have any conflicts of interest.

Additional information

Funding

AICTE (All India Council of Technical Education) provided the scholarship to the fellow for the project work.