Author(s):
Nadhifatun Nahdhia, Esti Hendradi, M. Agus Syamsur Rijal
Email(s):
nadhifatunnahdhia@gmail.com , esti-h@ff.unair.ac.id , muh-a-s-r@ff.unair.ac.id
DOI:
10.52711/0974-360X.2025.00320
Address:
Nadhifatun Nahdhia, Esti Hendradi, M. Agus Syamsur Rijal
Faculty of Pharmacy, Universitas Airlangga, Surabaya, 60115, Indonesia.
*Corresponding Author
Published In:
Volume - 18,
Issue - 5,
Year - 2025
ABSTRACT:
Diclofenac sodium is the most widely prescribed NSAIDs, but it has side effects on the GI tract. To overcome this, it can be formed in topical delivery. Diclofenac sodium is included in BCS class II with a log P value of 1.1. Diclofenac sodium can be designed in a nanoemulsion system to increase solubility and penetration effect on the skin. Nanoemulsion is a novel drug delivery consisting of two immiscible liquids, water and oil, which are stabilized by surfactant and cosurfactant. The components ratio of nanoemulsion must be appropriately combined to produce desirable properties, including small particle sizes and stable systems. Determining their optimal ratio is possible via the simplex lattice design (SLD) method. The SLD method was utilized as an optimization technique to generate model formulations of nanoemulsions by the nanoemulsion region extracted from the pseudo-ternary phase diagram. Nanoemulsion was prepared between water, oleic acid (oil), Tween 80-Span 80 (surfactant), and ethanol (cosurfactant) by low energy emulsification method. Their characteristics were evaluated. Tween 80-Span 80 and ethanol with a 2:1 ratio was chosen because they showed maximum nanoemulsion region. The optimal nanoemulsion formulation comprises 15.28% water, 21.25% oil, and 63.47% emulsifier. The results of nanoemulsion characteristics were good, with 108.8 nm particle size, 0.443 PDI, 99.8% transmittance, and 5.276 pH. The observed values were not significantly different from the predicted values. The utilization of the simplex lattice design method in the optimization of nanoemulsions is advantageous for the advancement of pharmaceutical development.
Cite this article:
Nadhifatun Nahdhia, Esti Hendradi, M. Agus Syamsur Rijal. Design and optimization of nanoemulsion system by simplex lattice design method to improve solubility of topical diclofenac sodium. Research Journal of Pharmacy and Technology. 2025;18(5):2237-3. doi: 10.52711/0974-360X.2025.00320
Cite(Electronic):
Nadhifatun Nahdhia, Esti Hendradi, M. Agus Syamsur Rijal. Design and optimization of nanoemulsion system by simplex lattice design method to improve solubility of topical diclofenac sodium. Research Journal of Pharmacy and Technology. 2025;18(5):2237-3. doi: 10.52711/0974-360X.2025.00320 Available on: https://rjptonline.org/AbstractView.aspx?PID=2025-18-5-43
REFERENCES:
1. Altman R. Bosch B. Brune K. Patrignani P. Young C. Advances in NSAID Development: Evolution of Diclofenac Products Using Pharmaceutical Technology. Drugs. 2015; 75(8): 859-877. doi.org/10.1007/s40265-015-0392-z
2. Sacha M. Faucon L. Hamon E. Ly I. Haltner-Ukomadu E. Ex Vivo Transdermal Absorption of A Liposome Formulation of Diclofenac. Biomedicine and Pharmacotherapy. 2019; 111(March 2019): 785-790. doi.org/10.1016/j.biopha.2018.12.079
3. Hendradi E. Rosita N. Rahmadhanniar E. Effect of Lipid Ratio of Stearic Acid and Oleic Acid on Characteristics of Nanostructure Lipid Carrier (NLC) System of Diethylammonium Diclofenac. Indonesian Journal of Pharmacy. 2017; 28(4): 198-204. doi.org/10.14499/indonesianjpharm28iss4pp198
4. Gan TJ. Diclofenac: An Update on Its Mechanism of Action and Safety Profile. Current Medical Research and Opinion. 2010; 26(7): 1715-1731. doi.org/10.1185/03007995.2010.486301
5. Rius B. Clària J. Principles, mechanisms of action, and future prospects of anti-inflammatory drugs. In NSAIDs and Aspirin: Recent Advances and Implications for Clinical Management. 2016; 17-34, Springer International Publishing. doi.org/10.1007/978-3-319-33889-7_2
6. Hamed R. Basil M. AlBaraghthi T. Sunoqrot S. Tarawneh O. Nanoemulsion-Based Gel Formulation of Diclofenac Diethylamine: Design, Optimization, Rheological Behavior and In Vitro Diffusion Studies. Pharmaceutical Development and Technology. 2015; 21(8): 980-989. doi.org/10.3109/10837450.2015.1086372
7. Donthi MR. Munnangi SR. Krishna KV. Saha RN. Singhvi G. Dubey SK. Nanoemulgel: A Novel Nano Carrier as a Tool for Topical Drug Delivery. Pharmaceutics. 2023; 15(164): 1-28. doi.org/10.3390/pharmaceutics15010164
8. Bashir M. Ahmad J. Asif M. et al. Nanoemulgel, An Innovative Carrier for Diflunisal Topical Delivery with Profound Anti-Inflammatory Effect: In Vitro and In Vivo Evaluation. International Journal of Nanomedicine. 2021; 16: 1457-1472. doi.org/10.2147/IJN.S294653
9. Nayak A. Mandal SK. Ramadan MA. Rath SK. Formulation, Development and Physicochemical Characterization of Diclofenac Topical Emulgel. Egyptian Journal of Chemistry. 2021; 64(3): 1563-1573. doi:10.21608/ejchem.2021.58467.3259
10. Agnihotri N. Soni GC. Prajapati SK. Chanchal DK. Khan A. Tiwari S. Formulation and Evaluation of Nanoemulsion for Targeting and Systemic Delivery of Diclofenac Sodium. Scholars Academic Journal of Pharmacy. 2019; 8(8): 376-393. doi:10.21276/sajp.2019.8.8.1
11. Ameliana L. Hendradi E. Yuwono M. Influence of Oleic Acid on The In Vitro Penetration of Diclofenac Sodium Gel. International Conference on Medicine and Health Sciences. 2016; 43-46. https://jurnal.unej.ac.id/index.php/prosiding/article/view/3887
12. Nagajyothi M. Pramod K. Bijin EN. Baby JN. Valsalakumari J. Nanoemulsified System of a Poorly Water Soluble Drug. Research Journal of Pharmaceutical Dosage Forms and Technology. 2015; 7(3): 169-174. doi.org/10.5958/0975-4377.2015.00025.7
13. Singh Y. Meher JG. Raval K. et al. Nanoemulsion: Concepts, Development and Applications in Drug Delivery. Journal of Controlled Release. 2017; 252: 28-49. doi.org/10.1016/j.jconrel.2017.03.008
14. Md S. Alhakamy NA. Aldawsari HM. et al. Improved Analgesic and Anti-Inflammatory Effect of Diclofenac Sodium by Topical Nanoemulgel: Formulation Development—In Vitro and In Vivo Studies. Journal of Chemistry. 2020; 2020: 1-10. doi.org/10.1155/2020/4071818
15. Jadhav RP. Koli VW. Kamble AB. Bhutkar MA. A Review on Nanoemulsion. Asian Journal of Research in Pharmaceutical Science. 2020; 10(2): 103-108. doi.org/10.5958/2231-5659.2020.00020.x
16. Saudagar RB. Vaishnav S. Pharmaceutical Nanoemulsion as a Rational Carrier for Drug Delivery. Research Journal of Pharmacy and Technology. 2016; 9(3): 298-304. doi.org/10.5958/0974-360X.2016.00055.X
17. Sujitha H. Reddy PA. Pavani S. Simplified Informative Study on Nanoemulsion. Research Journal of Pharmacy and Technology. 2013; 6(4): 325-335.
18. Abdesh and Gupta SK. Formulation and Evaluation of Nanoemulsion Based Nanoemulgel of Aceclofenac. Journal of Pharmaceutical Sciences and Research. 2020; 12(4): 524-532.
19. Ekshinge VB and Garala KC. Formulation Development of Tramadol Hydrochloride Rapid- Disintegrating Tablets Using Simplex Lattice Design. Research Journal of Pharmacy and Technology. 2009; 2(4):753-755.
20. Patel A. Gohel M. Soni T. Partial Least Square Analysis and Mixture Design for The Study of The Influence of Composition Variables on Nanoemulsions As Drug Carriers. Research Journal of Pharmacy and Technology. 2014; 7(12): 1446-1455.
21. Duangjit S. Mehr LM. Kumpugdee-Vollrath M. Ngawhirunpat T. Role of Simplex Lattice Statistical Design in The Formulation and Optimization of Microemulsions for Transdermal Delivery. Biological and Pharmaceutical Bulletin. 2014; 37(12): 1948-1957. doi.org/10.1248/bpb.b14-00549
22. Fithri NA. Mardiyanto M. Novita RP. Andrean V. Furosemide Self Nano Emulsifying Drug Delivery System (SNEDDS) Formulation Comprising of Capryol-90, Polysorbate-80, and PEG-400 with Simplex-Lattice-Design. Science and Technology Indonesia. 2017; 2(4): 85-88. doi.org/10.26554/sti.2017.2.4.85-88
23. Astuti IY. Marchaban M. Martien R. Nugroho AE. Design and Optimization of Self Nano-Emulsifying Drug Delivery System Containing a New Anti-Inflammatory Agent Pentagamavunon-0. Indonesian Journal of Chemistry. 2017; 17(3): 365-375. doi.org/10.22146/ijc.22640
24. Indrati O. Martien R. Rohman A. Nugroho AK. Application of Simplex Lattice Design on The Optimization of Andrographolide Self Nanoemulsifying Drug Delivery System (SNEDDS). Indonesian Journal of Pharmacy. 2020; 31(2): 124-130. doi:10.14499/indonesianjpharm31iss2pp124
25. Maskare RG. Indurwade NH. Deshmukh RA. Kuthe PV. Londhe PM. Deshmukh MT. Nanoemulsions: Increasing Possibilities In Oral Drug Delivery. Asian Journal of Pharmacy and Technology. 2021; 11(1): 53-58. doi.org/10.5958/2231-5713.2021.00009.x
26. Chauhan S. and Batra S. Development and In Vitro Characterization of Nanoemulsion Embedded Thermosensitive In-Situ Ocular Gel of Diclofenac Sodium for Sustained Delivery. International Journal of Pharmaceutical Sciences and Research. 2018; 9(6): 2301-2314. doi.org/10.13040/IJPSR.0975-8232.9(6).2301-14
27. Chong WT. Tan CP. Cheah YK. et al. Optimization of Process Parameters in Preparation of Tocotrienol-Rich Red Palm Oil-Based Nanoemulsion Stabilized by Tween 80-Span 80 Using Response Surface Methodology. PLoS One. 2018; 13(8): 1-22. doi.org/10.1371/journal.pone.0202771
28. Rebolleda S. Sanz MT. Benito JM. Beltrán S. Escudero I. González San-José ML. Formulation and Characterisation of Wheat Bran Oil-In-Water Nanoemulsions. Food Chemistry. 2015; 167: 16-23. doi.org/10.1016/j.foodchem.2014.06.097
29. Debnath S. Kumar GV. Satayanarayana SV. Design, Development and Evaluation of Novel Nanoemulsion of Terbinafine HCl. Research Journal of Pharmacy and Technology. 2012; 5(10): 1301-1307.
30. Erawati T. Hendradi E. Soeratri W. Praformulation Study of P-Methoxycinnamic Acid (PMCA) Nanoemulsion Using Vegetable Oils (Soybean Oil, Corn Oil, VCO). International Journal of Pharmacy and Pharmaceutical Sciences. 2014; 6(2): 99-101.
31. Suryani. Sahumena MH. Mabilla SY. et al. Preparation and Evaluation of Physical Characteristics of Vitamin E Nanoemulsion Using Virgin Coconut Oil (VCO) and Olive Oil as Oil Phase with Variation Concentration of Tween-80 Surfactant. Research Journal of Pharmacy and Technology. 2020; 13(7): 3232-3236. doi.org/10.5958/0974-360X.2020.00572.7
32. Gupta PK. Pandit JK. Narain PJ. Gupta RN. Gupta SK. Preparation of Diclofenac Diethylamine Nanoemulsions by Ultrasonication-Stability and Process Parameter Evaluation Under Various Conditions. Research Journal of Pharmaceutical Dosage Forms and Technology. 2011; 3(6): 285-293.
33. Gao L. Zhang D. Chen M. Drug Nanocrystals for The Formulation of Poorly Soluble Drugs and Its Application as a Potential Drug Delivery System. Journal of Nanoparticle Research. 2008; 10(5): 845-862. doi.org/10.1007/s11051-008-9357-4
34. Gurpreet K. and Singh SK. Review of Nanoemulsion Formulation and Characterization Techniques. Indian Journal of Pharmaceutical Sciences. 2018; 80(5): 781-789. doi.org/10.4172/pharmaceutical-sciences.1000422
35. Carreres-Prieto D. García JT. Carrillo JM. Vigueras-Rodríguez A. Towards Highly Economical and Accurate Wastewater Sensors by Reduced Parts of The LED-Visible Spectrum. Science of The Total Environment. 2023; 871(December 2022): 1-11. doi.org/10.1016/j.scitotenv.2023.162082
36. Manjunatha KM. Ramana M. Satyaranayana D. Design and Evaluation of Diclofenac Sodium Controlled Drug Delivery Systems. Indian Journal of Pharmaceutical Sciences. 2007; May-June: 384-389.
37. Rowe RC. Sheskey PJ. Cook WG. Quinn ME. Owen SC. Weller PJ. Handbook of Pharmaceutical Excipients, 7th Ed. 2012; The Pharmaceutical Press.