Chitosan-based buccal mucoadhesive patches to enhance the systemic bioavailability of tizanidine

ARPA M. D., Okur N. Ü., GÖK M. K., Özgümüş S., CEVHER E.

International Journal of Pharmaceutics, vol.642, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 642
  • Publication Date: 2023
  • Doi Number: 10.1016/j.ijpharm.2023.123168
  • Journal Name: International Journal of Pharmaceutics
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Keywords: Azelaic acid, Bioavailability, Buccal patch, Chitosan, Mucoadhesion, Tizanidine
  • Istanbul Medipol University Affiliated: Yes


Tizanidine hydrochloride (TZN) is a muscle relaxant used to treat a variety of disorders such as painful muscle spasms and chronic spasticity. TZN has low oral bioavailability due to extensive first-pass metabolism and is used orally at a dose of 6–24 mg per day. In the present study, buccal patches were prepared by solvent casting method using chitosan glutamate (Chi-Glu) and novel chitosan azelate (Chi-Aze) which was synthesised in-house for the first time, to enhance the bioavailability of TZN by bypassing first-pass metabolism. The characterisation, mucoadhesion and drug release studies were performed. Chi-Aze patches retained their integrity longer in the buccal medium and showed higher ex vivo drug permeability compared to that prepared with Chi-Glu. In vivo studies revealed that buccal formulation fabricated with Chi-Aze (3%) showed approx 3 times more bioavailability than the orally administered commercial product. Results of the studies indicate that Chi-Aze, prepared by conjugation of chitosan and a fatty acid, the patch formulation is a promising buccal mucoadhesive system due to the physical stability in buccal medium, the good mucoadhesiveness and the high TZN bioavailability. Moreover, Chi-Aze patch might be an alternative to oral formulations of TZN to reduce the dose and frequency of drug administration.