OPTIMIZATION, DEVELOPMENT, AND SAFETY EVALUATION OF OLIVE OIL NANOEMULSION FOR TOPICAL APPLICATION: A RESPONSE SURFACE METHODOLOGY

Authors

  • Wan Maznah Wan Ishak Faculty of Chemical and Process Engineering Technology, Universiti Malaysia Pahang, Gambang, Pahang, Malaysia.
  • Mohd Hanif Zulfakar Centre for Drug Delivery Technology, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia. https://orcid.org/0000-0003-0547-0370

DOI:

https://doi.org/10.22159/ajpcr.2022.v15i9.45964

Keywords:

olive oil, nanoemulsion, response surface methodology, skin irritation

Abstract

Objective: Nanoemulsions consist of fine oil-in-water dispersions, with droplets covering the size range of 50–500 nm. Olive oil is frequently utilized in cosmetic and pharmaceutical topical product for its healing, protecting, and moisturizing properties due to its high fatty acid and antioxidant content. In the present work, a nanoemulsion composed of olive oil, Span 80 as surfactant, and Labrasol as cosurfactant was developed using a high-pressure homogenization method and was evaluated for its physicochemical characteristics.

Methods: Response surface methodology was utilized to investigate the influence of the main nanoemulsion components: olive oil (X1), Span 80 (X2), and Labrasol (X3) on the droplet size (Y1) and polydispersity index (PDI) (Y2). A total of 17 formulations were generated by the Box-Behnken model.

Results: The model was found to be highly significant with R2 values of 0.9833 and 0.9382 for droplet size and PDI, respectively. The optimized nanoemulsion presented the droplet size of 144.2±0.8 nm and PDI of 0.105±0.014. Span 80 seems to be the most influential factor that determines the droplet size as it has higher significant linear and interaction effects. The developed nanoemulsion was, further, evaluated with an in vivo skin irritancy study using the rat model.

Conclusion: Results indicate that the developed nanoemulsion did not demonstrate any skin irritations in gross and histological examinations, suggesting that it is safe for topical applications.

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References

Tavakoli S, Klar AS. Advanced hydrogels as wound dressings. Biomolecules 2020;10:1169. doi: 10.3390/biom10081169, PMID 32796593

Silna EA, Krishnakumar K, Nair SK, Narayanan AV. Hydrogels in topical drug delivery-a review. Int J Innov Drug Discov 2016;6:87-93.

Bouchemal K, Briançon S, Perrier E, Fessi H. Nano-emulsion formulation using spontaneous emulsification: Solvent, oil and surfactant optimisation. Int J Pharm 2004;280:241-51. doi: 10.1016/j. ijpharm.2004.05.016, PMID 15265563

Abolmaali SS, Tamaddon AM, Farvadi FS, Daneshamuz S, Moghimi H. Pharmaceutical nanoemulsions and their potential topical and transdermal applications. Iran J Pharm Sci 2011;7:12.

Al-Edresi S, Baie S. In-vitro and in-vivo evaluation of a photo-protective kojic dipalmitate loaded into nano-creams. Asian J Pharm Sci 2010;16:251-65.

Rabasco Alvarez AM, González Rodríguez ML. Lipids in pharmaceutical and cosmetic preparations. Grasas Aceites 2000;51:74-96. doi: 10.3989/ gya.2000.v51.i1-2.409

Taguchi K, Fukushima S, Yamaoka Y, Takeuchi Y, Suzuki M. Enhancement of propylene glycol distribution in the skin by high purity cis-unsaturated fatty acids with different alkyl chain lengths having different double bond position. Biol Pharm Bull 1999;22:407-11. doi: 10.1248/bpb.22.407, PMID 10328563

Schürer N, Schliep V, Williams ML. Differential utilization of linoleic and arachidonic acid by cultured human keratinocytes. Skin Pharmacol 1995;8:30-40. doi: 10.1159/000211328, PMID 7786523

Cicerale S, Lucas L, Keast R. Biological activities of phenolic compounds present in virgin olive oil. Int J Mol Sci 2010;11:458-79. doi: 10.3390/ijms11020458, PMID 20386648

Ichihashi M, Ahmed NU, Budiyanto A, Wu A, Bito T, Ueda M, et al. Preventive effect of antioxidant on ultraviolet-induced skin cancer in mice. J Dermatol Sci 2000;23:S45-50. doi: 10.1016/s0923- 1811(00)00083-9, PMID 10764992

Cardoso CR, Souza MA, Ferro EA, Favoreto S, Pena JD. Influence of topical administration of n-3 and n-6 essential and n-9 nonessential fatty acids on the healing of cutaneous wounds. Wound Repair Regen 2004;12:235-43. doi: 10.1111/j.1067-1927.2004.012216.x, PMID 15086775

Bhatt P, Madhav S. A detailed review on nanoemulsion drug delivery system. Int J Pharm Sci Res 2011;2:2482-9.

McClements DJ. Nanoemulsions versus microemulsions: Terminology, differences, and similarities. Soft Matter 2012;8:1719-29. doi: 10.1039/ C2SM06903B

Wani TA, Ahmad A, Zargar S, Khalil NY, Darwish IA. Use of response surface methodology for development of new microwell-based spectrophotometric method for determination of atrovastatin calcium in tablets. Chem Cent J 2012;6:134. doi: 10.1186/1752-153X-6-134, PMID 23146143

Bezerra MA, Santelli RE, Oliveira EP, Villar LS, Escaleira LA. Response surface methodology (RSM) as a tool for optimization in analytical chemistry. Talanta 2008;76:965-77. doi: 10.1016/j.talanta.2008.05.019, PMID 18761143

Gunst RF. Response surface methodology: Process and product optimization using designed experiments. Technometrics 1996;38:284-6. doi: 10.1080/00401706.1996.10484509

Zainol S, Basri M, Basri HB, Shamsuddin AF, Abdul-Gani SS, Karjiban RA, et al. Formulation optimization of a palm-based nanoemulsion system containing levodopa. Int J Mol Sci 2012;13:13049- 64. doi: 10.3390/ijms131013049, PMID 23202937

Singh G, Pai RS, Devi VK. Response surface methodology and process optimization of sustained release pellets using Taguchi orthogonal array design and central composite design. J Adv Pharm Technol Res 2012;3:30-40. doi: 10.4103/2231-4040.93565, PMID 22470891

Aqil M, Kamran M, Ahad A, Imam SS. Development of clove oil based nanoemulsion of olmesartan for transdermal delivery: Box-behnken design optimization and pharmacokinetic evaluation. J Mol Liq 2016;214:238-48. doi: 10.1016/j.molliq.2015.12.077

More BH, Sakharwade SN, Tembhurne SV, Sakarkar DM. Evaluation for skin irritancy testing of developed formulations containing extract of Butea monosperma for its topical application. Int J Toxicol Appl Pharmacol 2013;3:10-3.

Hosseini S, Tarzi BG, Gharachorloo M, Ghavami M, Bakhoda H. Optimization on the stability of linseed oil-in-water nanoemulsions generated by ultrasonic emulsification using response surface methodology (RSM). Orient J Chem 2015;31:1223-30. doi: 10.13005/ojc/310282

Villar AM, Naveros BC, Campmany AC, Trenchs MA, Rocabert CB, Bellowa LH. Design and optimization of self-nanoemulsifying drug delivery systems (SNEDDS) for enhanced dissolution of gemfibrozil. Int J Pharm 2012;431:161-75. doi: 10.1016/j.ijpharm.2012.04.001, PMID 22498011

Ferreira SL, Bruns RE, Ferreira HS, Matos GD, David JM, Brandão GC, et al. Box-behnken design: An alternative for the optimization of analytical methods. Anal Chim Acta 2007;597:179-86. doi: 10.1016/j. aca.2007.07.011, PMID 17683728

Kotta S, Khan AW, Ansari SH, Sharma RK, Ali J. Formulation of nanoemulsion: A comparison between phase inversion composition method and high-pressure homogenization method. Drug Deliv 2013;22:455-66.

Alzorqi I, Ketabchi MR, Sudheer S, Manickam S. Optimization of ultrasound induced emulsification on the formulation of palm-olein based nanoemulsions for the incorporation of antioxidant β-D-Glucan polysaccharides. Ultrason Sonochem 2016;31:71-84. doi: 10.1016/j. ultsonch.2015.12.004, PMID 26964925

Barry-Ryan C, Gaston E, Frias JM, Burke R, Traynor M. Formation and stability of an oil in water emulsion containing lecithin, xanthan gum and sunflower oil. Int Food Res J. 2013;20(5):2173-81.

Hasani F, Pezeshki A, Hamishehkar H. Effect of surfactant and oil type on size droplets of betacarotene bearing nanoemulsions. Int J Curr Microbiol Appl Sci 2015;4:146-55.

Li PH, Chiang BH. Process optimization and stability of D-limonene-in-water nanoemulsions prepared by ultrasonic emulsification using response surface methodology. Ultrason Sonochem 2012;19:192-7. doi: 10.1016/j.ultsonch.2011.05.017, PMID 21680223

Chanana GD, Sheth BB. Particle size reduction of emulsions by formulation design-II: Effect of oil and surfactant concentration. PDA J Pharm Sci Technol 1995;49:71-6. PMID 7780748

Esquena J, Forgiarini A, González C, Solans C. Formation and stability of nanoemulsions in mixed nonionic surfactant systems. Prog Colloid Polym Sci 2001;118:184-9.

Shafiq S, Shakeel F, Talegaonkar S, Ahmad FJ, Khar RK, Ali M. Development and bioavailability assessment of ramipril nanoemulsion formulation. Eur J Pharm Biopharm 2007;66:227-43. doi: 10.1016/j. ejpb.2006.10.014, PMID 17127045

Modi JD, Patel JK. Nanoemulsion-based gel formulation of aceclofenac for topical delivery. Int J Pharm Pharm Sci Res 2011;1:6-12.

Çelik B, Sağıroğlu AA, Özdemir S. Design, optimization and characterization of coenzyme Q10-and D-Panthenyl triacetate-loaded liposomes. Int J Nanomedicine 2017;12:4869-78. doi: 10.2147/IJN. S140835, PMID 28744121

Mahdi ES, Noor AM, Sakeena MH, Abdullah GZ, Abdulkarim MF, Sattar MA. Formulation and in vitro release evaluation of newly synthesized palm kernel oil esters-based nanoemulsion delivery system for 30 % ethanolic dried extract derived from local phyllanthus urinaria for skin antiagin. Int J Nanomedicine 2011;6:2499-512. doi: 10.2147/ IJN.S22337, PMID 22072884

James O, Sunday AB. Evaluation of acute dermal irritation and wound contraction by Gymnema sylvestre and Datura Metel extracts in rats. Am J Biomed Life Sci 2014;2:83-8. doi: 10.11648/j.ajbls.20140204.14

Mitsuishi M, Oshikata T, Kumabe S, Kobayashi A, Katoku K, Kanno T, et al. Histological dermal changes caused by preparation and application procedures in percutaneous dose toxicity studies in dogs, rabbits and rats. J Toxicol Pathol 2015;28:1-9. doi: 10.1293/tox.2014-0021, PMID 26023255

Published

07-09-2022

How to Cite

Wan Ishak, W. M., and M. H. Zulfakar. “OPTIMIZATION, DEVELOPMENT, AND SAFETY EVALUATION OF OLIVE OIL NANOEMULSION FOR TOPICAL APPLICATION: A RESPONSE SURFACE METHODOLOGY”. Asian Journal of Pharmaceutical and Clinical Research, vol. 15, no. 9, Sept. 2022, pp. 167-73, doi:10.22159/ajpcr.2022.v15i9.45964.

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