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Applied Clinical Research, Clinical Trials and Regulatory Affairs

Editor-in-Chief

ISSN (Print): 2213-476X
ISSN (Online): 2213-4778

Research Article

Development and Characterization of Water-in-Oil Microemulsion for Transdermal Delivery of Eperisone Hydrochloride

Author(s): Monika D. Kumbhar*, Manisha S. Karpe and Vilasrao J. Kadam

Volume 7, Issue 1, 2020

Page: [45 - 64] Pages: 20

DOI: 10.2174/2213476X06666190318120522

Abstract

Background: Eperisone hydrochloride possesses short biological half-life due to first pass metabolism resulting in low bioavailability and short duration of response with toxic effects, ultimately limits its utilization for treatment of muscle spasm.

Objective: In view of this background, current study was designed for the development of Eperisone hydrochloride-loaded microemulsion and Eperisone hydrochloride-loaded microemulsion based cream for topical delivery and compared it with conventional cream.

Methods: Firstly, water-in-oil microemulsion was prepared by spontaneous emulsification method. The concentration of components was found out from existence of microemulsion region by constructing pseudoternary phase diagram. The oil was selected on the basis of drug solubility effect on the drug release, whereas surfactant and cosurfactant were screened on the basis of their efficiency to form microemulsion region. The influence of components on microemulsion formation, drug release capacity, permeation was studied by differential scanning calorimetry, X-ray diffraction, in-vitro release and ex-vivo drug permeation studies respectively. By using microemulsion, the cream was prepared for proving optimum structure for topical application. Microemulsion was evaluated for droplet size, zeta potential, pH, viscosity and conductivity. Besides the cream was characterized for pH, rheology and stability. Permeation of EPE from microemulsion across the rat skin was evaluated and compared with conventional cream.

Results: The microemulsion consisting Isopropyl Myristrate/Water/Span 80:Tween 80 (50/8/42% by weight) possessed droplet size of 95.77nm, zeta potential of −5.23 mV with 7.25 pH and conductivity near to zero (<0.05mScm-1). Physical parameters of the cream were satisfactory, also 2.33-fold higher permeation and 1.57-fold higher release observed as compared to conventional cream.

Conclusion: It can be concluded that Eperisone hydrochloride-loaded microemulsion and its cream is being effectively used for muscle spasticity by topical route.

Keywords: Eperisone hydrochloride, transdermal delivery, water-in-oil microemulsion, sustained release, Permeation, metabolism.

Graphical Abstract

[1]
Nisijima K, Shirnizu M, Ishiguro T. Treatment of tardive dystonia with an antispastic agent. Acta Psychiatr Scand 1998; 98(4): 341-3.
[2]
Bose K. The efficacy and safety of eperisone in patients with cervical spondylosis: results of a randomized, double-blind, placebo-controlled trial. Method fined exp clin 1999; 21(3): 209-14.
[3]
Tanaka K, Kaneko T, Yamatsu K. Effects of 4'ethyl- 2-methyl-3 piperidinopropiophenone on experimental rigidity and spinal cord activities (author's transl). Folia pharmacologica Japonica 1981; 77(5): 511-20.
[4]
Mihara K, Matsumura M, Yoshioka E, et al. Intestinal first-pass metabolism of eperisone in the rat. Pharma Res 2001; 18(8): 1131-7.
[5]
Matsunaga M, Uemura Y, Yonemoto Y, et al. Long-lasting muscle relaxant activity of eperisone hydrochloride after percutaneous administration in rats. J Pharmacol Sci 1997; 73(3): 215-20.
[6]
Schäfer-Korting M, Mehnert W, Korting HC. Lipid nanoparticles for improved topical application of drugs for skin diseases. Adv Drug Deliv Reviews 2007; 59(6): 427-43.
[7]
Yang SI, Park HY, Lee SH, et al. Transdermal eperisone elicits more potent and longer-lasting muscle relaxation than oral eperisone. Pharmacol 2004; 71(3): 150-6.
[8]
Prausnitz MR, Langer R. Transdermal drug delivery. Nat Biotechnol 2008; 26(11): 1261.
[9]
Kogan A, Garti N. Microemulsions as transdermal drug delivery vehicles. Adv Colloid Interface Sci 2006; 123: 369-85.
[10]
Schaefer H, Redelmeier TE. Skin barrier: principles of percutaneous absorption. 1st ed. Basel, Switzerland 1996; pp. 35-7.
[11]
Vicentini FT, Vaz MM, Fonseca YM, Bentley MV, Fonseca MJ. Characterization and stability study of a water-in-oil microemulsion incorporating quercetin. Drug Dev Ind Pharm 2011; 37(1): 47-55.
[12]
Shafiq-un-Nabi S, Shakeel F, Talegaonkar S, et al. Formulation development and optimization using nanoemulsion technique: a technical note. AAPS PharmSciTech 2007; 8(2): E12-7.
[13]
Sakeena MH, Muthanna FA, Ghassan ZA, et al. Formulation and in vitro evaluation of ketoprofen in palm oil esters nanoemulsion for topical delivery. J Oleo Sci 2010; 59(4): 223-8.
[14]
Zhang Y, Gao J, Zheng H, Zhang R, Han Y. The preparation of 3, 5-dihydroxy-4-isopropylstilbene nanoemulsion and in vitro release. Int J Nanomedicine 2011; 6: 649.
[15]
Neubert RH. Potentials of new nano carriers for dermal and transdermal drug delivery. Eur J Pharm Biopharm 2011; 77(1): 1-2.
[16]
Rhee YS, Choi JG, Park ES, Chi SC. Transdermal delivery of ketoprofen using microemulsions. Int J Pharma 2001; 228 1(2): 161-70.
[17]
Zhao X, Liu JP, Zhang X, Li Y. Enhancement of transdermal delivery of theophylline using microemulsion vehicle. Int J Pharma 2006; 327(2): 58-64.
[18]
Benson HA, Watkinson AC. Skin structure, function, and permeation Topical and transdermal drug delivery: principles and practice. John Wiley & Sons, Inc. 2012; pp. 409-46.
[19]
Avdeef A. Solubility of sparingly soluble ionizable drugs. Adv Drug Deliv Rev 2007; 59(7): 568-90.
[20]
Chen H, Chang X, Weng T, et al. A study of microemulsion systems for transdermal delivery of triptolide. J Control Release 2004; 98(3): 427-36.
[21]
Al-Adham IS, Ashour H, Al-Kaissi E, Khalil E, Kierans M, Collier PJ. Studies on the kinetics of killing and the proposed mechanism of action of microemulsions against fungi. Int J pharma 2013; 454(1): 226-32.
[22]
Baboota S, Al-Azaki A, Kohli K, Ali J, Dixit N, Shakeel F. Development and evaluation of a microemulsion formulation for transdermal delivery of terbinafine. PDA J Pharm Sci Technol 2007; 61(4): 276-85.
[23]
Jadhav KR, Shetye SL, Kadam VJ. Design and evaluation of microemulsion based drug delivery system. Int J Advances in Pharma Sci 2010; 1(2)
[24]
Okur NÜ, Yavaşoğlu A, Karasulu HY. Preparation and evaluation of microemulsion formulations of naproxen for dermal delivery. Chem Pharm Bull 2014; 62(2): 135-43.
[25]
Jain J, Fernandes C, Patravale V. Formulation development of parenteral phospholipid-based microemulsion of etoposide. Aaps PharmSciTech 2010; 11(2): 826-31.
[26]
Muthu MS, Singh S. Poly (D, L-lactide) nanosuspensions of risperidone for parenteral delivery: formulation and in-vitro evaluation. Curr Drug Deliv 2009; 6(1): 62-8.
[27]
Aggarwal N, Goindi S, Mehta SD. Preparation and evaluation of dermal delivery system of griseofulvin containing vitamin E-TPGS as penetration enhancer. AAPS PharmSciTech 2012; 13(1): 67-74.
[28]
Lawrence MJ, Rees GD. Microemulsion-based media as novel drug delivery systems. Adv Drug Deliv Rev 2012; 64(1): 175-93.
[29]
Sharma N, Bansal M, Visht S, Sharma PK, Kulkarni GT. Nanoemulsion: A new concept of delivery system. Chron Young Sci 2010; 1(2): 2.
[30]
Farahpour MR, Habibi M. Evaluation of the wound healing activity of an ethanolic extract of Ceylon cinnamon in mice. Vet Med 2012; 57(1): 53-7.
[31]
Ridd MJ, Redmond NM, Hollinghurst S, et al. Choice of Moisturiser for Eczema Treatment (COMET): study protocol for a randomized controlled trial. Trials 2015; 16(1): 304.
[32]
Lachman L, Lieberman HA. Kanig M Martin Emulsions, in the theory and practice of industrial pharmacy Philadelphia. Lea & Febiger. New York 3rd ed.. 1990; pp. 1-909.
[33]
Tadros T. Principles of emulsion stabilization with special reference to polymeric surfactants. J Cosmet Sci 2006; 57(2): 153-69.
[34]
Teixeira GF, Vieira-Neto AE, da Costa FN, e Silva AR, Campos AR. Antinociceptive effect of (-)-α-bisabolol in nanocapsules. Biomed & Pharmaco 2017; 91: 946-50.
[35]
Mishra BK, Kuanar M, Chauhan G, Patel N. Behaviour of non-ionic Inicroe1nulsion containing Tween-80, iso-amyl alcohol, hexane and water. Indian J Chem Technol 2000; 7: 338-41.
[36]
Shi J, Xue SJ, Wang B, Wang W, Ye X, Quek SY. Optimization of formulation and influence of environmental stresses on stability of lycopene-microemulsion. LWT-Food Sci Techn 2015; 60(2): 999-1008.
[37]
Wakita K, Kuwabara H, Furusho N, Tatebe C, Sato K, Akiyama H. A comparative study of the hydroxyl and saponification values of polysorbate 60 in international food additive specifications. Am J Anal Chem 2014; 5(3): 199.
[38]
Bumajdad A, Eastoe J. Conductivity of water-in-oil microemulsions stabilized by mixed surfactants. J Colloid Interface Sci 2004; 274(1): 268-76.
[39]
Anjali CH, Dash M, Chandrasekaran N, Mukherjee A. Antibacterial activity of sunflower oil microemulsion. Int J Pharm Pharm Sci 2010; 2(1): 123-8.
[40]
Arshad AI, Khan SH, Akhtar NA. Formulation development of topical cream loaded with ananas comosus extract: in vivo evaluation for changes in skin barrier function using biophysical techniques. Acta Pol Pharm 2016; 73(2): 485-94.
[41]
Goldberg-Cettina M, Liu P, Nightingale J, Kurihara-Bergstrom T. Enhanced transdermal delivery of estradiol in vitro using binary vehicles of isopropyl myristate and short-chain alkanols. Int J Pharm 1995; 114(2): 237-45.
[42]
Chen H, Mou D, Du D, et al. Hydrogel-thickened microemulsion for topical administration of drug molecule at an extremely low concentration. Int J Pharma 2007; 341(1-2): 78-84.
[43]
Som I, Bhatia K, Yasir M. Status of surfactants as penetration enhancers in transdermal drug delivery. J Pharma bioallied sci 2012; 4(1) : 2.

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