Formulation development and characterization of flucinolone acetonide nanoemulsion for ocular drug delivery system

Chetan Amrutkar; Sanjay B.  Patil

doi:10.69857/joapr.v13i5.1501

Authors

Chetan Amrutkar Department of Pharmaceutics, SNJB’s SSDJ College of Pharmacy, Neminagar, Chandwad, Nashik-423101, Maharashtra- 411007, India
Sanjay B. Patil Department of Pharmaceutics, SNJB’s SSDJ College of Pharmacy, Neminagar, Chandwad, Nashik-423101, Maharashtra- 411007, India

DOI:

https://doi.org/10.69857/joapr.v13i5.1501

Keywords:

Flucinolone acetonide, Macular edema, Posterior uveitis, Nano-emulsion, Ex vivo permeation, Cell line

Abstract

Background: The purpose of this study is to enhance and demonstrate the effectiveness of the corticosteroid drug fluocinolone acetonide in the form of an ophthalmic nanoemulsion. This formulation is designed to improve targeted delivery and ocular penetration, making it suitable for the treatment of conditions such as age-related macular degeneration, diabetic macular edema, and posterior uveitis. Methodology: To formulate the nanoemulsion, we used polysorbate 20 and a castor oil derivative known as HCO-40. The continuous emulsification method was employed to prepare the formulation. Initial batches were tested for key properties, including pH, osmolality, drug content, globule size, and zeta potential. A factorial design approach was applied, in which polysorbate 20 and the castor oil derivative (Cremophor RH 40) were considered independent variables. The nanoemulsion was further evaluated for ocular irritancy using cell line analysis, in vitro scleral permeability, and the Hen’s Egg Chorioallantoic Membrane (HET-CAM) test. Results and Discussion: The optimized batch of the nanoemulsion showed a penetration rate exceeding 80% and a small globule size of 19–20 nm. In vitro tests using human retinal pigment epithelial (ARPE-19) cells and the HET-CAM test indicated that the formulated nanoemulsion is non-toxic and non-irritating to the eye, confirming its cytocompatibility. Conclusion: The developed optimized nanoemulsion formulation of flucinolone acetonide provides improved targeting, non-invasive administration & enhanced patient compliance when used as a topical eye drop for treating ocular diseases such as age-related macular degeneration and posterior uveitis.

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References

Salama AH, Mahmoud AA, Kamel R. A Novel Method for Preparing Surface-Modified Fluocinolone Acetonide Loaded PLGA Nanoparticles for Ocular Use: In Vitro and In Vivo Evaluations. AAPS PharmSciTech, 17, 1159-72 (2016) https://doi.org/10.1208/s12249-015-0448-0.

Bucolo C, Drago F, Salomone S. Ocular drug delivery: a clue from nanotechnology. Front Pharmacol, 25, 188 (2012) https://doi.org/10.3389/fphar.2012.00188.

Amrutkar CS, Patil SB. Nanocarriers for ocular drug delivery: Recent advances and future opportunities. Indian journal of ophthalmology, 71, 2355-2366 (2023) https://doi.org/10.4103/ijo.ijo_1893_22.

Wang R, Gao Y, Liu A, Zhai G, A review of nanocarrier mediated drug delivery systems for posterior segment eye disease: challenges analysis and recent advances. Journal of Drug Targeting, 29, 1-31 (2021) https://doi.org/10.1080/1061186X.2021.1878366.

Hemnani N, Suresh P, Fabrication and study of release kinetics of moxifloxacin and dexamethasone loaded nanostructured lipid carrier system for ocular drug delivery. Journal of applied pharmaceutical research, 13, 141 – 153 (2025) https://doi.org/10.69857/joapr.v13i3.1162.

Cunha-Vaz J, Ashton P, Iezzi R, Campochiaro P, Dugel P, Holz F et al. Sustained delivery fluocinolone acetonide vitreous implants: long term benefit in patients with chronic diabetic macular edema. Ophthalmology, 121, 1892-903 (2014) https://doi.org/10.1016/j.ophtha.2014.04.019.

Kane FE, Green KE, Ocular Pharmacokinetics of Fluocinolone Acetonide Following Iluvien Implantation in the Vitreous Humor of Rabbits. J Ocul Pharmacol Ther., 31, 11-6 (2015) https://doi.org/10.1089/jop.2014.0100

Kempen JH, Altaweel MM, Holbrook JT, Jabs DA, Sugar EA. The Multicenter Uveitis Steroid Treatment (MUST) Trial: Rationale, Design and Baseline Characteristics. Am J Ophthalmol., 149, 550–561 (2010) https://doi.org/10.1016/j.ajo.2009.11.019.

Fernández RV, Tomé VD, Rodríguez AL, Penedo AC, Otero XG, Álvarez AL, et al. Drug Delivery to the Posterior Segment of the Eye: Biopharmaceutic and Pharmacokinetic Considerations. Pharmaceutics, 12, 269 (2020) https://doi.org/10.3390/pharmaceutics12030269.

Dean E, Kumar RP. Surgical management of intraocular inflammation and infection. New Delhi: JP Medical Publishers. 1/e, 126 (2013) https://doi.org/10.5005/jp/books/11926.

Schmit-Eilenberger VK. A novel intravitreal fluocinolone acetonide implant (Iluvien((R)) in the treatment of patients with chronic diabetic macular edema that is insufficiently responsive to other medical treatment options: a case series. Clin Ophthalmol. 9, 801-11 (2015) https://doi.org/10.2147/Opth.S79785.

Cunha-Vaz J, Ashton P, Iezzi R, Campochiaro P, Dugel PU, Holz FG. Sustained delivery fluocinolone acetonide vitreous implants: long-term benefit in patients with chronic diabetic macular edema. Ophthalmology, 121, 1892–903 (2014) https://doi.org/10.1016/j.ophtha.2014.04.019.

Parekh A, Srivastava S, Bena J, Albini T, Nguyen QD, Goldstein DA. Risk factors associated with intraocular pressure increase in patients with uveitis treated with the fluocinolone acetonide implant. JAMA Ophthalmol., 133, 568–73 (2015) https://doi.org/10.1001/jamaophthalmol.2015.51.

Galdino MB, Sandeep Jain S, Simon Kaja S. Ocular Pharmacokinetic Studies: Challenges and Best Practices. Challenges and Best Practices [Internet]. Pharmacokinetics and Pharmacogenetics - Principles, Applications, and Challenges [Working Title]. IntechOpen; 2025 http://doi.org/10.5772/intechopen.1011599.

Cao Y, Samy KE, Bernards DA, Desai TA. Recent advances in intraocular sustained-release drug delivery devices, Drug Discov. Today, 24, 1694–1700 (2019) https://doi.org/10.1016/j.drudis.2019.05.031.

Han H, Li S, Xu M, Zhong Y, Fan W, Xu J, Zhou T, Ji J, Ye J, Yao K. Polymer- and lipid-based nanocarriers for ocular drug delivery: Current status and future perspectives. Advanced Drug Delivery Reviews, 196, 114770 (2023) https://doi.org/10.1016/j.addr.2023.114770.

Agrahari V, Mandal A, Agrahari V, Trinh HM, Joseph M, Ray A et al. A comprehensive insight on ocular pharmacokinetics. Drug Deliv. and Transl. Res., 6, 735–754 (2016) https://doi.org/10.1007/s13346-016-0339-2.

Bansal P, Garg, S, Sharma Y, Venkatesh P. Posterior Segment Drug Delivery Devices: Current and Novel Therapies in Development. J Ocul Pharmacol Ther., 32, 135-44 (2016) https://doi.org/10.1089/jop.2015.0133.

Parmar K, Patel JK, Bhatia, D. Pathak, YV. Drug Delivery for the Retina and Posterior Segment Disease. Springer International Publishing, 397−409 (2018) https://doi.org/10.1007/978-3-319-95807-1.

Cholkar K, Gunda S, Earla R, Pal D, Mitra AK. Nanomicellar Topical Aqueous Drop Formulation of Rapamycin for Back-of-the-Eye Delivery. AAPS PharmSciTech, 16, 610−22 (2015) https://doi.org/10.1208/s12249-014-0244-2.

Nayak K, Misra M. Triamcinolone Acetonide-Loaded PEGylated Microemulsion for the Posterior Segment of Eye. ACS Omega, 5, 7928-39 (2020) https://doi.org/10.1021/acsomega.9b04244.

Algahtani MS, Ahmad MZ, Ahmad J. Nanoemul gel for improved topical delivery of retinyl palmitate: Formulation design and stability evaluation. Nanomaterials (Basel), 10, 848 (2020) https://doi.org/10.3390/nano10050848.

Arumugam S, Balabaskaran S, Abhilash BA, Sowmiya K, Baalann KP, Surya BN. Study of risk factors in myopic individuals among medical students in Chennai, Tamil Nadu. Journal of applied pharmaceutical research, 11, 10-14 (2023) https://doi.org/10.18231/j.joapr.2023.11.4.10.14.

Khalid N, Shu G, Holland BJ, Kobayashi I, Nakajima M, Barrow CJ. Formulation and characterization of O/W nanoemulsions encapsulating high concentration of astaxanthin. Food Res. Int. 102, 364-371 (2017) https://doi.org/10.1016/j.foodres.2017.06.019.

Prasad D, Mohanta GP, Sudhakar M. A review on preparation and evaluation of nanoemulsions. International Journal of Pharma Research and Health Sciences, 7, 2915-22(2019) https://doi.org/10.21276/ijprhs.2019.01.11.

Ustundag-Okur N, Gokçe EH, Eğrilmez S, Ozer O, Ertan G. Novel ofloxacin-loaded microemulsion formulations for ocular delivery. Journal of Ocular Pharmacology and Therapeutics, 30, 319-32 (2014) https://doi.org/10.1089/jop.2013.0114.

Jacob S, Nair AB, Shah J. Emerging role of nanosuspensions in drug delivery systems. Biomater Res., 24, 3 (2020) https://doi.org/10.1186/s40824-020-0184-8.

Harun S, Nordin SA, Abd Gani SS, Shamsuddin AF, Basri M, Bin Basri H. Development of nanoemulsion for efficient brain parenteral delivery of cefuroxime: Designs, characterizations, and pharmacokinetics. Int J Nanomedicine, 13, 2571-2584 (2018) https://doi.org/10.2147/IJN.S151788.

Dave V, Paliwal S, Yadav S, Sharma S. Effect of in vitro transcorneal approach of aceclofenac eye drops through excised goat, sheep, and buffalo corneas. Scientific World Journal, 7 (2015) https://doi.org/10.1155/2015/432376.

Alambiaga-Caravaca AM, Calatayud-Pascual MA, Rodilla V, Angel Concheiro A, López-Castellano A, Alvarez-Lorenzo C. Micelles of Progesterone for Topical Eye Administration: Interspecies and Intertissues Differences in Ex Vivo Ocular Permeability. Pharmaceutics, 12, 702 (2020) https://doi.org/10.3390/pharmaceutics12080702.

Sapino S, Chindamo G, Peira E, Chirio D, Foglietta F, Serpe L, Vizio B, Gallarate M. Development of ARPE-19-Equipped Ocular Cell Model for In Vitro Investigation on Ophthalmic Formulations. Pharmaceutics. 15, 2472 (2023) https://doi.org/10.3390/pharmaceutics15102472.

Rivero MN , Lenze M , Izaguirre M , Damonte SH , Aguilar A, Gutiérrez ML. Comparison between HET-CAM protocols and a product use clinical study for eye irritation evaluation of personal care products including cosmetics according to their surfactant composition. Food Chem Toxicol, 153, 112229 (2021) https://doi.org/10.1016/j.fct.2021.112229.

Viera LM , Silva RS , Silva CC , Presgrave OA , Boas MHS. Comparison of the different protocols of the Hen's Egg Test-Chorioallantoic Membrane (HET-CAM) by evaluating the eye irritation potential of surfactants. Toxicol In Vitro, 78, 105255 (2022) https://doi.org/10.1016/j.tiv.2021.105255.

Shaikh S, Desai S, Jain H, Sahu A, Meshram DB. Formulation and evaluation of in situ ophthalmic gel of loteprednol etabonate. Journal of applied pharmaceutical research, 9, 1-7 (2021) https://doi.org/10.18231/j.joapr.2021.25.29