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Current Drug Delivery

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ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

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Research Article

Development of Biocompatible Nanoparticles of Tizanidine Hydrochloride in Orodispersible Films: In vitro Characterization, Ex vivo Permeation, and Cytotoxic Study on Carcinoma Cells

Author(s): Suhani Sinha, Sonia Thapa, Shashank Singh, Rohit Dutt*, Ravinder Verma, Parijat Pandey, Vineet Mittal, Md. Habibur Rahman and Deepak Kaushik*

Volume 19, Issue 10, 2022

Published on: 25 May, 2022

Page: [1061 - 1072] Pages: 12

DOI: 10.2174/1567201819666220321111338

Price: $65

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.

Keywords: Chitosan-alginate nanoparticles, ionotropic pregelation, spasticity, permeability, in vitro dissolution, solvent casting.

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[1]
20397 Zanaflex. Available from: https://www.accessdata.fda.gov/ drugsatfda_docs/nda/97/020397Orig1s000rev.pdf (Accessed May 17, 2021).
[2]
Nance, P.W.; Bugaresti, J.; Shellenberger, K.; Sheremata, W.; Martinez-Arizala, A. Efficacy and safety of tizanidine in the treatment of spasticity in patients with spinal cord injury. North American tizanidine study group. Neurology, 1994, 44(11)(Suppl. 9), S44-S51.
[PMID: 7970010]
[3]
D’Alessandro, R.; Granella, F. Tizanidine for chronic cluster headache. Arch. Neurol., 1996, 53(11), 1093.
[http://dx.doi.org/10.1001/archneur.1996.00550110021002] [PMID: 8912480]
[4]
Zanaflex. Available from: https://www.accessdata.fda.gov/drugsatfda_ docs/nda/2002/21447_Zanaflex_BioPharmr.pdf (Accessed May 17, 2021).
[5]
Henney, H.R., III; Chez, M. Pediatric safety of tizanidine: Clinical adverse event database and retrospective chart assessment. Paediatr. Drugs, 2009, 11(6), 397-406.
[http://dx.doi.org/10.2165/11316090-000000000-00000] [PMID: 19877725]
[6]
Sinha, S.; Dutt, R. Oral soluble films: Attributes of the polymeric material and critical process parameters for designing good quality films. Curr. Appl. Polym. Sci., 2019, 3(3), 167-188.
[http://dx.doi.org/10.2174/2452271603666191210121944]
[7]
Arya, A.; Chandra, A.; Sharma, V.; Pathak, K. Fast dissolving oral films: An innovative drug delivery system and dosage form. Int. J. Chemtech Res., 2010, 2, 576-583.
[8]
Ehtezazi, T.; Algellay, M.; Hardy, A. Next steps in 3D printing of fast dissolving oral films for commercial production. Recent Adv. Drug Deliv. Formulation, 2020, 14(1), 5-20.
[http://dx.doi.org/10.2174/1872211314666191230115851] [PMID: 31886755]
[9]
Gijare, C.; Deshpande, A. Orodispersible films: A systematic patent review. Recent Adv. Drug Deliv. Formulation, 2018, 12(2), 110-120.
[http://dx.doi.org/10.2174/1872211312666180509100216] [PMID: 29745346]
[10]
Soroushnai, A.; Ganji, F.; Vasheghani-Farahani, E.; Mobedi, H. Development and evaluation of an anti-epileptic oral fast-dissolving film with enhanced dissolution and in vivo permeation. Curr. Drug Deliv., 2018, 15(9), 1294-1304.
[http://dx.doi.org/10.2174/1567201815666180723115600] [PMID: 30033870]
[11]
Mahesh, A.; Shastri, N.; Sadanandam, M. Development of taste masked fast disintegrating films of levocetirizine dihydrochloride for oral use. Curr. Drug Deliv., 2010, 7(1), 21-27.
[http://dx.doi.org/10.2174/156720110790396454] [PMID: 19863484]
[12]
Li, P.; Dai, Y.N.; Zhang, J.P.; Wang, A.Q.; Wei, Q. Chitosan-alginate nanoparticles as a novel drug delivery system for nifedipine. Int. J. Biomed. Sci., 2008, 4(3), 221-228.
[PMID: 23675094]
[13]
Shen, B.D.; Shen, C.Y.; Yuan, X.D.; Bai, J.X.; Lv, Q.Y.; Xu, H.; Dai, L.; Yu, C.; Han, J.; Yuan, H.L. Development and characterization of an orodispersible film containing drug nanoparticles. Eur. J. Pharm. Biopharm., 2013, 85(3 Pt B), 1348-1356.
[http://dx.doi.org/10.1016/j.ejpb.2013.09.019] [PMID: 24103635]
[14]
Barak, M.F.; Lerner, I.E.; Rosenberger, V. Pharmaceutical compositions and dosage forms for buccal and sublingual delivery of tizanidine and methods of delivering tizanidine sublingually or bucally. AU2003287488B2, 2003.
[15]
Shanker, G.; Kumar, C.K.; Gonugunta, C.S.R.; Kumar, B.V.; Veerareddy, P.R. Formulation and evaluation of bioadhesive buccal drug delivery of tizanidine hydrochloride tablets. AAPS PharmSciTech, 2009, 10(2), 530-539.
[http://dx.doi.org/10.1208/s12249-009-9241-2] [PMID: 19424804]
[16]
Patel, D.; Naik, S.; Misra, A. Improved transnasal transport and brain uptake of tizanidine HCl-loaded thiolated chitosan nanoparticles for alleviation of pain. J. Pharm. Sci., 2012, 101(2), 690-706.
[http://dx.doi.org/10.1002/jps.22780] [PMID: 22006260]
[17]
Mazzarino, L.; Borsali, R.; Lemos-Senna, E. Mucoadhesive films containing chitosan-coated nanoparticles: A new strategy for buccal curcumin release. J. Pharm. Sci., 2014, 103(11), 3764-3771.
[http://dx.doi.org/10.1002/jps.24142] [PMID: 25187001]
[18]
Karagianni, A.; Peltonen, L. Production of itraconazole nanocrystal-based polymeric film formulations for immediate drug release. Pharmaceutics, 2020, 12(10), 960.
[http://dx.doi.org/10.3390/pharmaceutics12100960] [PMID: 33065968]
[19]
USP35-NF30, Tizanidine HCl tablets analytical method. , 4878.
[20]
El-Newehy, M.H.; El-Hamshary, H.; Salem, W.M. Solution blowing spinning technology towards green development of urea sensor nanofibers immobilized with hydrazone probe. Polymers (Basel), 2021, 13(4), 531.
[http://dx.doi.org/10.3390/polym13040531] [PMID: 33670291]
[21]
Jing-jing, G.; Peng-Fei, Y.; Jun-lan, L. JinHana, S.; FuaShi, X.; JinaShi, Y.; Hai-Long, Y. Development and in vivo/in vitro evaluation of novel herpetrione nanosuspension. Int. J. Pharm., 2013, 4, 227-233.
[22]
Chonkar, A.D.; Rao, J.V.; Managuli, R.S.; Mutalik, S.; Dengale, S.; Jain, P.; Udupa, N. Development of fast dissolving oral films containing lercanidipine HCl nanoparticles in semicrystalline polymeric matrix for enhanced dissolution and ex vivo permeation. Eur. J. Pharm. Biopharm., 2016, 103, 179-191.
[http://dx.doi.org/10.1016/j.ejpb.2016.04.001] [PMID: 27063592]
[23]
Kevadiya, B.D.; Barvaliya, M.; Zhang, L.; Anovadiya, A.; Brahmbhatt, H.; Paul, P.; Tripathi, C. Fenofibrate nanocrystals embedded in oral strip-films for bioavailability enhancement. Bioengineering (Basel), 2018, 5(1), 1.
[http://dx.doi.org/10.3390/bioengineering5010016] [PMID: 29438297]
[24]
Shiledar, R.R.; Tagalpallewar, A.A.; Kokare, C.R. Formulation and in vitro evaluation of xanthan gum-based bilayered mucoadhesive buccal patches of zolmitriptan. Carbohydr. Polym., 2014, 101(101), 1234-1242.
[http://dx.doi.org/10.1016/j.carbpol.2013.10.072] [PMID: 24299896]
[25]
Kilor, V.; Sapkal, N.; Daud, A.; Humne, S.; Gupta, T. Development of stable nanosuspension loaded oral films of glimepiride with improved bioavailability. Int. J. Appl. Pharm., 2017, 9(2), 28-33.
[http://dx.doi.org/10.22159/ijap.2017v9i2.16714]
[26]
Liu, C.; Chang, D.; Zhang, X.; Sui, H.; Kong, Y.; Zhu, R.; Wang, W. Oral fast-dissolving films containing lutein nanocrystals for improved bioavailability: Formulation development, in vitro and in vivo evaluation. AAPS PharmSciTech, 2017, 18(8), 2957-2964.
[http://dx.doi.org/10.1208/s12249-017-0777-2] [PMID: 28462465]
[27]
Bharti, K.; Mittal, P.; Mishra, B. Formulation and characterization of fast dissolving oral films containing buspirone hydrochloride nanoparticles using design of experiment. J. Drug Deliv. Sci. Technol., 2019, 49, 420-432.
[http://dx.doi.org/10.1016/j.jddst.2018.12.013]
[28]
Qing, S.; Chengying, S.; Baode, S.; Wangquan, L.; Xiao, L. Bo, Dai.; Hailong, Y. Development of a fast-dissolving sublingual film containing meloxicam nanocrystals for enhanced dissolution and earlier absorption. J. Drug Deliv. Sci. Technol., 2018, 2, 243-252.
[29]
Castro, P.M.; Baptista, P.; Madureira, A.R.; Sarmento, B.; Pintado, M.E. Combination of PLGA nanoparticles with mucoadhesive guar-gum films for buccal delivery of antihypertensive peptide. Int. J. Pharm., 2018, 547(1-2), 593-601.
[http://dx.doi.org/10.1016/j.ijpharm.2018.05.051] [PMID: 29800740]
[30]
Li, X.Q.; Ye, Z.M.; Wang, J.B.; Fan, C.R.; Pan, A.W.; Li, C.; Zhang, R.B. Filmes bucais mucoadesivos de tramadol para o controle eficaz da dor mucoadhesive buccal films of tramadol for effective pain management. Rev. Bras Anestesiol., 2017, 67(3), 231-237.
[http://dx.doi.org/10.1016/j.bjan.2016.10.006]
[31]
Esposito, E.; Mariani, P.; Ravani, L.; Contado, C.; Volta, M.; Bido, S.; Drechsler, M.; Mazzoni, S.; Menegatti, E.; Morari, M.; Cortesi, R. Nanoparticulate lipid dispersions for bromocriptine delivery: Characterization and in vivo study. Eur. J. Pharm. Biopharm., 2012, 80(2), 306-314.
[http://dx.doi.org/10.1016/j.ejpb.2011.10.015] [PMID: 22061262]

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