Optimization of Microemulgel for Tizanidine Hydrochloride

Author(s): Swati Jagdale*, Sujata Brahmane, Anuruddha Chabukswar

Journal Name: Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents)

Volume 19 , Issue 2 , 2020

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: Tizanidine hydrochloride acts centrally as a muscle relaxant. It is used for the treatment of painful muscle spasm, spasticity associated with multiple sclerosis or spinal cord injury and treatment of muscle spasticity in spinal cord disease. Tizanidine hydrochloride belongs to BCS class II. It has low oral bioavailability and short halflife. Incorporating this drug in microemulgel is an excellent way to overcome problems associated with the drug.

Objectives: Present research work was aimed to develop and optimize a microemulsion based gel system for tizanidine hydrochloride.

Methods: Screening of oil, surfactant and co-surfactant was carried out. Ternary phase diagram was constructed to obtain concentration range of components. The prepared microemulsion was evaluated for pH, globule size, zeta potential, conductivity, density and viscosity. 32 level factorial design was applied to study the effect of concentration of carbopol 934 and HPMC K15M on % cumulative drug release and viscosity of microemulgel using software Design Expert. Microemulgel was evaluated for pH, spreadability, viscosity, syneresis, drug content, bioadhesive strength, in-vitro as well as ex-vivo diffusion study.

Results: Microemulsion was prepared by using isopropyl myristate as oil, tween 80 as a surfactant and transcutol P as cosurfactant. Largest transparent microemulsion region was found with Smix ratio of 1:1. FE-SEM showed globule size 28μm for batch B1 and zeta potential was -1.27mV indicating good stability of the microemulsion. Optimised batch was F6 which showed 92% drug release within 8 hours. It followed the Korsmeyer-Peppas model.

Conclusion: A stable, effective and elegant microemulgel formulation, exhibiting good in-vitro and ex-vivo drug release was formulated.

Keywords: Delivery, emulsion, factorial, gel, microemulgel, microemulsion, tizanidine.

[1]
Shah, M.; Dixit, M.; Shah, D. A new future approach in novel drug delivery system through microemulgel. Review WJPPS, 2016, 5(5), 243-259.
[2]
Singla, V.; Saini, S.; Joshi, B.; Rana, A. Emulgel: A new platform for topical drug delivery. Int. J. Pharma Bio Sci., 2012, 3(1), 485-498.
[http://dx.doi.org/10.22159/ijcpr.2017v9i1.16628]
[3]
Shah, C.; Shah, D. A review on microemulsion based gel: a novel approach for enhancing topical delivery of hydrophobic drug. Int J. Pharm. Pharma. Res., 2017, 8(4), 19-35.
[4]
Notes on data of the drug tizanidine hydrochloride, www.pubchem.ncbi.nlm.gov/tizanidinehydrochloride (Accessed on 27 June, 2016). www.pubchem.ncbi.nlm.gov/tizanidinehydrochloride
[5]
Notes on data of the drug tizanidine hydrochloridev www.chemspider.com/tizanidinehydrochloride (Accessed on 20 July 2016).
[6]
Trivedi, S.; Upadhyay, N.; Sudhakar, C.; Jain, S. Transdermal administration of tizanidine hydrochloride using elastic vesicles: characterisation and in vivo permeation studies. Asian J. Pharm., 2013, 3(3), 29-45.
[7]
Vinod, P.; Howard, I.S.; Jenner, M.J. Topical Drug Bioavailability, Bioequivalence, and Penetration; Springer-Verlag: New York publisher, 2014, pp. 1-402.
[8]
Soni, P; Gat, G.V.; Nithiyanandam, R.; Panda, R.R. Pharmaceutical composition of tizanidine and process for preparing the same. WO 2016/139681 A2, 2016.
[9]
Borsa, M. Pharmaceutical dosage forms of tizanidine and administration routes thereof. EP 2 338 473 A1, 2016.
[10]
Barak, M.F.; Judelman, A.G. . Tizanidine compositions and methods of treatment using the compositions. WO2007016676A1 2007.
[11]
Pellegrini, C.; Stark, P. Method of tizanidine therapy. US20030176472A1 2003.
[12]
Pravallika, K.; Ravi, P.; Lalitha, D.; Hemavathi, K.; Bhavya, M.; Ravi, P. Development and validation of UV spectroscopic method for analysis of tizanidine hydrochloride. WJPR, 2014, 3(10), 428-427.
[13]
Barot, B.S.; Parejiya, P.B.; Patel, H.K.; Gohel, M.C.; Shelat, P.K. Microemulsion-based gel of terbinafine for the treatment of onychomycosis: optimization of formulation using D-optimal design. AAPS PharmSciTech, 2012, 13(1), 184-192.
[http://dx.doi.org/10.1208/s12249-011-9742-7] [PMID: 22187363]
[14]
Moghimipour, E.; Salimi, A.; Eftekhari, S. Design and characterization of microemulsion systems for naproxen. Adv. Pharm. Bull., 2013, 3(1), 63-71.
[http://dx.doi.org/10.5681/ apb.2013.011] [PMID: 24312814]
[15]
Basheer, H.; Noordin, M.; Ghareeb, M. Characterisation of microemulsion prepared using isopropyl palmitate with various surfactants and cosurfactants. Trop. J. Pharm. Res., 2012, 12(3), 305-310.
[16]
Patel, M.; Parikh, J.; Patel, R. Novel isotretinoinmicroemulsion based gel for targeted topical therapy of acne: formulation, consideration, skin retension and skin irritation studies. Appl. Nanosci., 2016, 6, 539-553.
[http://dx.doi.org/10.1007/s13204-015-0457-z]
[17]
Jagdale, S.; Chaudhari, B. Optimization of microemulsion based transdermal gel of triamcinolone. Recent Pat Antiinfect Drug Discov, 2017, 12(1), 61-78.
[http://dx.doi.org/10.2174/1574891X12666170426092911] [PMID: 28506203]
[18]
Thakur, N.K.; Bharti, P.; Mahant, S.; Rao, R. Formulation and characterization of benzoyl peroxide gellified emulsions. Sci. Pharm., 2012, 80(4), 1045-1060.
[http://dx.doi.org/10.3797/scipharm.1206-09] [PMID: 23264949]
[19]
Government of India. Ministry of health and welfare, 2014.
[20]
Moghimipour, E.; Salimi, A.; Leis, F. Preparation and evaluation of tretinoin microemulsion based on pseudo-ternary phase diagram. Adv. Pharm. Bull., 2012, 2(2), 141-147.
[PMID: 24312785]
[21]
Jagdale, S.; Pawar, S. Gellified emulsion of ofloxacin for transdermal drug delivery system. Adv. Pharm. Bull., 2017, 7(2), 229-239.
[http://dx.doi.org/10.15171/apb.2017.028] [PMID: 28761825]
[22]
Aggarwal, N.; Goindi, S.; Khurana, R. Formulation, characterization and evaluation of an optimized microemulsion formulation of griseofulvin for topical application. Colloids Surf. B Biointerfaces, 2013, 105, 158-166.
[http://dx.doi.org/10.1016/j.colsurfb.2013.01.004] [PMID: 23357739]
[23]
Barot, B.S.; Parejiya, P.B.; Patel, H.K.; Mehta, D.M.; Shelat, P.K.; Shelat, P. Microemulsion-based antifungal gel delivery to nail for the treatment of onychomycosis: formulation, optimization, and efficacy studies. Drug Deliv. Transl. Res., 2012, 2(6), 463-476.
[http://dx.doi.org/10.1007/s13346-012-0109-8] [PMID: 25787325]
[24]
Trivedi, S.; Uppadhyay, N.; Sudhakar, C. Transdermal administration of tizanidine hydrochloride using elastic vesicles: characterization and in vitro permeation studies. Asian J. Pharm. Sci. Res., 2013, 3(3), 29-45.
[25]
Chinese Pharmacopeia. China Medical Science Press. A, 2010, II, p. 238, A242. 2010.
[26]
Indian Pharmacopeia. Indian Pharmacopeia Commission: Ghaziabad, I, 2010, pp. 189-191.
[27]
Jagdale, S.; Bari, N.; Kuchekar, B.; Chabukswar, A. Study on the effect of HPMC on compression coated floating pulsatile delivery of bisoprolol. Curr. Drug Ther., 2014, 9(2), 93-103.
[http://dx.doi.org/10.2174/1574885509666140115213810]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 19
ISSUE: 2
Year: 2020
Page: [158 - 179]
Pages: 22
DOI: 10.2174/1871523018666190308123100

Article Metrics

PDF: 21
HTML: 2
EPUB: 1
PRC: 1