Title:Development of Biocompatible Nanoparticles of Tizanidine Hydrochloride
in Orodispersible Films: In vitro Characterization, Ex vivo Permeation,
and Cytotoxic Study on Carcinoma Cells
Volume: 19
Issue: 10
Author(s): Suhani Sinha, Sonia Thapa, Shashank Singh, Rohit Dutt*, Ravinder Verma, Parijat Pandey, Vineet Mittal, Md. Habibur Rahman and Deepak Kaushik*
Affiliation:
- Department of Pharmacy, School of Medical and Allied Sciences, G.D. Goenka University, Gurugram-122103, India
- Department of Pharmaceutical Sciences, M.D. University, Rohtak (124001), Haryana, India
Keywords:
Chitosan-alginate nanoparticles, ionotropic pregelation, spasticity, permeability, in vitro dissolution, solvent casting.
Abstract:
Background: The main limitations of the therapeutic effectiveness of tizanidine hydrochloride
(TNZ) are its low bioavailability due to its tendency to undergo first-pass metabolism and short
biological half-life. These factors make it an ideal candidate for formulating orally disintegrating films.
Objective: The present study was aimed to prepare nanoparticles of tizanidine hydrochloride using biodegradable
polymers and loading them on orodispersible films to obtain a sustained release dissolution
profile with improved permeability and further study the cytotoxicity on A549 lung carcinoma cells,
MCF7 breast cancer cells, and HOP 92 non-small lung adenocarcinoma cells.
Methods: The fast-dissolving film of TNZ HCl was prepared by the solvent-casting method and characterized
using scanning electron microscopy, FTIR, and XRD, and evaluated for critical quality attributes
for this type of dosage form such as disintegration time, tensile strength, drug content, dissolution, and
ex vivo permeability. In vitro cytotoxicity studies were also conducted on cancer cell lines to confirm
the cytotoxic effect.
Results: The polymeric matrix containing the drug provided a rapid disintegration time varying between
7±2 and 30±2 seconds, adequate tensile strength between 1.4 and 11.25 N/mm2, and improved permeability
through porcine buccal mucosa when compared to the reference product.
Conclusion: A study of the cytotoxic effect on the MCF-7 breast cancer cells and A549 lung carcinoma
cells revealed that tizanidine hydrochloride nanoparticles at 2.3 mg/film exhibited an IC50 value of
65.1 % cytotoxicity on MCF-7, approximately 100% on HOP92, and 83.5 % on A549 lung carcinoma
cells, thus paving the way for a new paradigm of research for a cytotoxic study on MCF-7, HOP92, and
A549 cell lines using the subject drug model prepared as oral films or biodegradable nanoparticles in
oral films for site-specific targeting.
