FORMULATION, OPTIMIZATION AND CHARACTERIZATION OF IBUPROFEN LOADED MICROEMULSION SYSTEM USING D-OPTIMAL MIXTURE DESIGN

Authors

  • YASSIR EL ALAOUI Laboratory of Pharmaceutics, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco
  • AICHA FAHRY Laboratory of Pharmaceutics, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco
  • YOUNES RAHALI Laboratory of Pharmaceutics, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco
  • NAWAL CHERKAOUI Laboratory of Pharmaceutics, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco
  • YAHYA BENSOUDA Laboratory of Pharmaceutics, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco
  • ABDELKADER LAATIRIS Laboratory of Pharmaceutics, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco

DOI:

https://doi.org/10.22159/ijap.2019v11i4.33076

Keywords:

Microemulsion, Ibuprofen, Mixture design, Surfactant, Co-surfactant

Abstract

Objective: The purpose of this study was to develop, optimize and characterize a stable microemulsion, with an improvement of the solubility of a poorly aqueous soluble drug, ibuprofen.

Methods: Various oils (oleic acid, cottonseed oil, olive oil, argan oil, and labrafac® WL 1349), surfactants (tween® 80, tween® 40, tween® 20) and co-surfactants including polyethylene glycol 400, ethanol, 1-butanol, and propylene glycol were selected after solubility studies. Then, pseudo-ternary phase diagrams with surfactant/co-surfactant ratio of 1:2, 1:1, 2:1 and 3:1 were constructed and a D-optimal mixture design method was used to optimize the ibuprofen loaded microemulsion. The optimized microemulsion was evaluated for several characteristics including globule size, zeta potential, pH, conductivity, refractive index and stability studies.

Results: Optimized microemulsion obtained was composed of oleic acid (6.88% w/w), tween® 80/1-butanol (3:1, 63.11% w/w) and water (30.00% w/w). The results obtained showed an average globule size of 117.5 nm, a zeta potential of-6.47 mV and a transmittance of 96.95±0.77%. The optimized formulation showed an improvement in the solubility of ibuprofen with unchanged characteristics for one month.

Conclusion: The use of pseudo-ternary phase diagrams and mathematical modeling allows to obtain an optimal microemulsion with perfect stability for 1 mo and a better solubilization capacity of ibuprofen.

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References

Bushra R, Aslam N. An overview of clinical pharmacology of Ibuprofen. Oman Med J 2010;25:155-61.

Rainsford KD. Ibuprofen: pharmacology, efficacy and safety. Inflammopharmacology 2009;17:275-342.

Irvine J, Afrose A, Islam N. Formulation and delivery strategies of ibuprofen: challenges and opportunities. Drug Dev Ind Pharm 2018;44:173-83.

Lewis F, Connolly MP, Bhatt A. A pharmacokinetic study of an ibuprofen topical patch in healthy male and female adult volunteers. Clin Pharmacol Drug Dev 2018;7:684-91.

Nagai N, Tanino T, Ito Y. Pharmacokinetic studies of gel system containing ibuprofen solid nanoparticles. J Oleo Sci 2016;65:1045-53.

Aliberti ALM, de Queiroz AC, Praca FSG, Eloy JO, Bentley M, Medina WSG. Ketoprofen microemulsion for improved skin delivery and in vivo anti-inflammatory effect. AAPS PharmSciTech 2017;18:2783-91.

Xing Q, Song J, You X, Xu D, Wang K, Song J, et al. Microemulsions containing long-chain oil ethyl oleate improve the oral bioavailability of piroxicam by increasing drug solubility and lymphatic transportation simultaneously. Int J Pharm 2016;511:709-18.

Priano L, Albani G, Brioschi A, Calderoni S, Lopiano L, Rizzone M, et al. Transdermal apomorphine permeation from microemulsions: a new treatment in Parkinson's disease. Mov Disord 2004;19:937-42.

Cao M, Ren L, Chen G. Formulation optimization and ex vivo and in vivo evaluation of celecoxib microemulsion-based gel for transdermal delivery. AAPS PharmSciTech 2017;18:1960-71.

Hashem FM, Shaker DS, Ghorab MK, Nasr M, Ismail A. Formulation, characterization, and clinical evaluation of microemulsion containing clotrimazole for topical delivery. AAPS PharmSciTech 2011;12:879-86.

Dogrul A, Arslan SA, Tirnaksiz F. Water/oil type microemulsion systems containing lidocaine hydrochloride: in vitro and in vivo evaluation. J Microencapsulation 2014;31:448-60.

Kawakami K, Yoshikawa T, Hayashi T, Nishihara Y, Masuda K. Microemulsion formulation for enhanced absorption of poorly soluble drugs. II. In vivo study. J Controlled Release 2002;81:75-82.

Lawrence MJ, Rees GD. Microemulsion-based media as novel drug delivery systems. Adv Drug Delivery Rev 2012;64:175-93.

Tole K, G Deshmukh. Design and characterization of microemulsion gel for transdermal drug delivery system of duloxetine hydrochloride. Asian J Pharm Clin Res 2018;11:157-61.

Talegaonkar S, Azeem A, Ahmad F, Khar R, A Pathan S, Iqbal Z. Microemulsions: a novel approach to enhanced drug delivery. Recent Pat Drug Delivery Formulation 2008;2:238-57.

Narang AS, Delmarre D, Gao D. Stable drug encapsulation in micelles and microemulsions. Int J Pharm 2007;345:9-25.

Jaiswal PL, Darekar AB, Saudagar RB. A recent review on nasal microemulsion for the treatment of cns disorder. Int J Curr Pharm Res 2017;9:5-13.

Sanjaymitra PvSS, Ganesh GNK. Dissolution and solubility enhancement strategies: Current and novel prospectives. J Crit Rev 2018;5:1-10.

Chen H, Chang X, Du D, Li J, Xu H, Yang X. Microemulsion-based hydrogel formulation of ibuprofen for topical delivery. Int J Pharm 2006;315:52-8.

Sabale V, Vora S. Formulation and evaluation of microemulsion-based hydrogel for topical delivery. Int J Pharm Invest 2012;2:140-9.

Djekic L, Primorac M, Filipic S, Agbaba D. Investigation of surfactant/cosurfactant synergism impact on ibuprofen solubilization capacity and drug release characteristics of nonionic microemulsions. Int J Pharm 2012;433:25-33.

Gustmann PC. Development of Brazil nut oil microemulsion as vehicle for levamisole. J Appl Pharm Sci 2017;7:92-8.

Junyaprasert VB, Boonme P, Songkro S, Krauel K, Rades T. Transdermal delivery of hydrophobic and hydrophilic local anesthetics from o/w and w/o Brij 97-based microemulsions. J Pharm Pharm Sci 2007;10:288-98.

Shah N, Seth A, Balaraman R, Sailor G, Javia A, Gohil D. Oral bioavailability enhancement of raloxifene by developing microemulsion using D-optimal mixture design: optimization and in vivo pharmacokinetic study. Drug Dev Ind Pharm 2018;44:687-96.

Mandal S, Das Mandal S, Chuttani K, Subudhi bb. Mucoadhesive microemulsion of ibuprofen: design and evaluation for brain targeting efficiency through intranasal route. Braz J Pharm Sci 2015;51:721-31.

Zhu W, Yu A, Wang W, Dong R, Wu J, Zhai G. Formulation design of microemulsion for dermal delivery of penciclovir. Int J Pharm 2008;360:184-90.

Hua L, Weisan P, Jiayu L, Ying Z. Preparation, evaluation, and NMR characterization of vinpocetine microemulsion for transdermal delivery. Drug Dev Ind Pharm 2004;30:657-66.

Fanun M. Celecoxib solubilization in nonionic microemulsions. J Dispersion Sci Technol 2010;31:241-7.

Hu L, Hu Q, Yang J. Enhancement of transdermal delivery of ibuprofen using microemulsion vehicle. Iran J Basic Med Sci 2014;17:760-6.

Xavier Junior FH, Vauthier C, Morais ARV, Alencar EN, Egito EST. Microemulsion systems containing bioactive natural oils: an overview on the state of the art. Drug Dev Ind Pharm 2016;43:1-15.

Mauludin R, SF Bt Mohamad, T Suciati. Formulation and characterization of ascorbyl palmitate loaded o/w microemulsion. Int J Pharm Pharm Sci 2014;6:294-8.

Kumar A, Kushwaha V, Sharma P. Pharmaceutical microemulsion: formulation, characterization and drug deliveries across skin. Int J Drug Dev Res 2014;6:1-21.

Kilor V, N Sapkal, G Vaidya. Design and development of novel microemulsion based topical formulation of hesperidin. Int J Pharm Pharm Sci 2015;7:142-8.

Desai SA, Mohite RA, Hajare A. Screening of safflower oil microemulsion for enhancing bioavailability of lovastatin. Int J Pharm Sci Res 2015;6:28-49.

Date AA, Nagarsenker MS. Design and evaluation of microemulsions for improved parenteral delivery of propofol. AAPS PharmSciTech 2008;9:138-45.

Date AA, Nagarsenker MS. Parenteral microemulsions: an overview. Int J Pharm 2008;355:19-30.

Shah KA, Joshi MD, Patravale VB. Biocompatible microemulsions for fabrication of glyceryl monostearate solid lipid nanoparticles (SLN) of tretinoin. J Biomed Nanotechnol 2009;5:396-400.

Kale NJ, Allen LV. Studies on microemulsions using Brij 96 as surfactant and glycerin, ethylene glycol and propylene glycol as cosurfactants. Int J Pharm 1989;57:87-93.

Yati K, Srifiana Y, Putra F. Effect of optimization of tween 80 and propylene glycol as a surfactant and cosurfactant on the physical properties of aspirin microemulsion. Int J Appl Pharm 2017;9:127-9.

Wang X, Xue M, Gu J, Fang X, Sha X. Transdermal microemulsion drug delivery system for impairing male reproductive toxicity and enhancing efficacy of tripterygium wilfordii hook f. Fitoterapia 2012;83:690-8.

Abd Allah FI, Dawaba HM, Ahmed AM. Preparation, characterization, and stability studies of piroxicam-loaded microemulsions in topical formulations. Drug Discoveries Ther 2010;4:267-75.

Subramanian N, Ghosal SK, Moulik SP. Topical delivery of celecoxib using microemulsion. Acta Pol Pharm 2004;61:335-41.

Biruss B, Valenta C. The advantage of polymer addition to a non-ionic oil in water microemulsion for the dermal delivery of progesterone. Int J Pharm 2008;349:269-73.

Pereira Lachataignerais J, Pons R, Panizza P, Courbin L, Rouch J, Lopez O. Study and formation of vesicle systems with low polydispersity index by ultrasound method. Chem Phys Lipids 2006;140:88-97.

Patel V, Kukadiya H, Mashru R, Surti N, Mandal S. Development of microemulsion for solubility enhancement of clopidogrel. Iran J Pharm Res 2010;9:327-34.

Shah P, Swarnkar D, Parikh R. Development and characterization of microemulsion containing antihypertensive agent using factorial design. J Pharm Bioallied Sci 2012;4(Suppl 1):69-70.

Djekic L, Martinovic M, Stepanovic Petrovic R, Micov A, Tomic M, Primorac M. Formulation of hydrogel-thickened nonionic microemulsions with enhanced percutaneous delivery of ibuprofen assessed in vivo in rats. Eur J Pharm Sci 2016;92:255-65.

Published

07-07-2019

How to Cite

ALAOUI, Y. E., FAHRY, A., RAHALI, Y., CHERKAOUI, N., BENSOUDA, Y., & LAATIRIS, A. (2019). FORMULATION, OPTIMIZATION AND CHARACTERIZATION OF IBUPROFEN LOADED MICROEMULSION SYSTEM USING D-OPTIMAL MIXTURE DESIGN. International Journal of Applied Pharmaceutics, 11(4), 304–312. https://doi.org/10.22159/ijap.2019v11i4.33076

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