Submit Manuscript | Track Article | Contact
IJAPH Logo

International Journal of Advanced Pharmaceutical and Healthcare

Peer-reviewed | Open Access | International Journal

ISSN 3144-5055

Development and Characterization of a SMEDDS-Based in Situ Ophthalmic Drug Delivery System for Nepafenac

2026/10/1
VOLUME 1, ISSUE 3
Research Article
Published

Authors

Sheeshpalsinh Solanki, Jaini K. Patel*, Amar M. Raval, Dr. Disha Suthar, Priyanka Yadav

Abstract

Topical ocular instillation remains the preferred route for treating anterior segment ocular disorders, however, conventional eye drops exhibit notoriously low ocular bioavailability (< 5%) due to stringent physiological barriers, including rapid nasolacrimal drainage, blinking reflex, and the impermeability of the corneal epithelium. This challenge is significantly magnified for Nepafenac, a BCS Class II nonsteroidal anti-inflammatory prodrug whose extremely poor aqueous solubility (0.014 mg/mL) severely limits therapeutic permeation across lipophilic-hydrophilic corneal layers. To overcome these dual physiological and physicochemical bottlenecks, this study developed and evaluated an integrated nanocarrier-hydrogel platform: a Self-Microemulsifying Drug Delivery System (SMEDDS) embedded in an ion-activated in situ gelling matrix. The optimized lipid phase comprised Capryol 90 (oil), Cremophor RH 40 (surfactant), and PEG 400 (co-surfactant), which upon aqueous dispersion yielded optical clarity (99.34% transmittance), a mean globule size of 206.1 nm, and an electrostatically stabilizing zeta potential of −17.1 mV. Incorporation into a Gellan gum/HPMC polymeric system facilitated an instantaneous sol-to-gel phase transition (3 seconds) in the presence of simulated tear fluid conditions. Rheological assessment demonstrated a sharp transition from a freely pourable Newtonian sol (48 cps) to a viscoelastic pseudoplastic gel (8190 cps), resisting premature precorneal drainage. In vitro permeation profiles exhibited biphasic kinetics characterized by an initial burst release (25–30% within the first hour) followed by sustained diffusion over 6 hours, achieving 99.45% cumulative drug release for the optimized batch F7. Accelerated stability testing (40°C/75% RH for 1 month) confirmed no phase separation and robust chemical integrity with an assay of 95.32%. This dual delivery system presents a clinically promising approach to maximize transcorneal flux, enhance precorneal retention, and minimize dosing frequency.

Keywords

Nepafenac SMEDDS (Self-Microemulsifying Drug Delivery System) In situ ophthalmic gel Ion-activated gelation Gellan gum Precorneal residence time Ocular bioavailability Sustained release.

References

  1. Gaballa SA, Saleh MG, Kompella UB, Alany RG, Abdelkader H. Non‐Steroidal Anti‐Inflammatory Drugs (NSAIDs): Ocular Pharmacology, Pharmaceutical Innovations, and Drug Delivery Perspectives. Advanced Therapeutics, 2026 May; 9(5): e00580.
  2. Vashi R, Sorathia K. Novel stable micellar formulation for ocular delivery of nepafenac: optimization, characterization and in-vitro evaluation. Drug Development and Industrial Pharmacy, 2026 Mar 4; 52(3): 557-69.
  3. Devi S, Saini V, Mehan N, Kumar M, Mujtaba MA, Elhassan GO, Haider N, Warsi MH. Development and Evaluation of Prednisolone Acetate-Loaded Nanostructured Lipid Carriers Integrated into pH-Triggered In Situ Gels for Ocular Drug Delivery. ASSAY and Drug Development Technologies, 2026 Jan 1; 24(1): 49-64.
  4. Bakhrushina EO, Leonova KS, Belyavsky NO, Gegechkori VI, Belyaev VV, Sysuev BB, Salakhetdinov DK, Krasnyuk II, Atkova EL, Yartsev VD. Punctal and Intracanalicular Drug Delivery Systems for Ophthalmic Use: A Narrative Review of Technologies, Clinical Outcomes, and Critical Quality Attributes. Pharmaceutics, 2026 Jul 7; 18(7): 830.
  5. Subhash NE, Prabhu M, Hazarika M, S S, Bhandary SV, Guru BR. Advances in the management of ocular anterior segment diseases using biomaterials-based drug delivery systems. Journal of Biomaterials Applications, 2026 Jan; 40(6): 666-89.
  6. Toprak G. Novel Trauma Drug Treatment Delivery Systems for Ocular. Modern Approaches to Ocular Trauma Diagnosis Management and Rehabilitation, 2026 Apr 1: 351.
  7. El-Emam KR, El-Masry AA, Elmansi H, El-Gohary NS. Fabrication of Fe-Mn mixed oxide nanosheets via microwave assistance as an advanced probe for ultra-sensitive nepafenac sensing in diverse matrices, paving the way for future applications. BMC chemistry, 2026 May 30; 20(1): 117.
  8. Choi Y, Jung MY, Han E, Park CY. Recent Advances in Extended Ocular Drug Delivery for the Ocular Surface. Molecules, 2026 May 31; 31(11): 1883.
  9. Alatas F, Ammarullah W. Chitosan-Based In-Situ Gels for Topical Drug Delivery: A Review of Mechanisms, Applications, and Future Prospects. Jurnal Ilmu Farmasi dan Farmasi Klinik, 2026 May 1; 23(1): 73-88.
  10. Kumar N, Kumar A, Kumar S. ONE-POT FABRICATION OF A BETAXOLOL HYDROCHLORIDE-LOADED NANOSTRUCTURED LIPID CARRIER THERMO-RESPONSIVE OCULAR NANOGEL FOR ENHANCED CORNEAL PERMEATION AND RETENTION. Genetics and Molecular Research, 2026 Sep 14.
  11. Patil MA, Matter BA, Santana C, Kompella UB. Interspecies scaling of suprachoroidal drug delivery using ocular geometry and drug physicochemical properties. Scientific Reports, 2026 Jan 16; 16(1): 4502.
  12. Raval MA, Suthar MA, Durani MB, Thakar MN, Zankhwala MF, Kushkiwala MA, Rathod MS. Smart Co-Processed Excipient Platforms: A Novel Strategy for Multifunctional Optimization of Ibuprofen Tablet Formulations. Practice, 2025; 1: 2.
  13. Huang W, Wen Z, Tourmouzis K, Huang L, Goldstein SM, Natke E, Honkanen R, Rigas B. Phosphosulindac (OXT-328) restores the suppressed corneal sensitivity in rabbits with dry eye disease: therapeutic implications. Frontiers in Drug Delivery, 2026 Jun 3; 6: 1778440.
  14. Zankhwala MF, Raval MA, Kushkiwala MA, Sarvaiya MS, Raval MK, Thakar MN, Barjod MS. Formulation And Evaluation Of Optimized Polymer Blends For Diclofenac Diethylamine Transdermal System. The Review of Diabetic Studies, 2025 Sep 14; 701-8.
  15. Raval AM, Ratnakar BP, Utpalkumar PF, Utpalkumar PV. Development and Evaluation of Multifunctional Co-Processed Excipients for Fast Dissolving Tablet Formulation. Asian Journal of Pharmaceutical Research and Development, 2026 Apr 15; 14(2): 226-33.
  16. Omer S, Nagy N, Szőcs E, Kádár S, Völgyi G, Pinke B, Mészáros L, Katona G, Vincze A, Dormán P, Nagy ZZ. Development of innovative electrospun nepafenac-loaded nanofibers-based ophthalmic inserts. International Journal of Pharmaceutics, 2023 Nov 25; 647: 123554.
  17. Patra RN, Shah KR, Mishra A, Halder J, Sahoo RK, Rajwar TK, Pradhan D, Dash P, Das C, Rai VK, Manoharadas S. Design and characterization of preservative free nepafenac loaded polyvinyl alcohol nanofiber for the treatment of dry eye syndrome. Polymers for Advanced Technologies, 2025 Dec; 36(12): e70437.
  18. Chandragirivar PC, Banu A, Raval AM, Kusuma R, Srinidhi G, Yashwanth HB, Suheel A. Improved Dissolution Performance of Fenoprofen Calcium Using PEG 6000 Solid Dispersions: Preparation by Fusion Method and Physicochemical Characterization. Int J Drug Deliv Technol, 2026; 16(36s): 771-81.
  19. Vincze A, Facskó R, Budai-Szűcs M, Katona G, Gyarmati B, Csorba A, Zelkó R, Nagy ZZ, Szente L, Balogh GT. Cyclodextrin-enabled nepafenac eye drops with improved absorption open a new therapeutic window. Carbohydrate Polymers, 2023 Jun 15; 310: 120717.
  20. Khandai M, Panda SK, Sahoo DK, Zankhwala FM, Raval MA, Suthar MA, Gupta MA, Khade MS. Artificial Intelligence in Precision Drug Delivery: From Machine Learning to Intelligent Nanomedicine. International Journal of Artificial Intelligence and Machine Learning, 2026 Sep 14; 6(10s): 56-68.
  21. Singh S, Singh S, Khandelwal V, Singh AP, Sachan K, Singh PK. Novel Approach and Recent Advancement In-Situ Gel as Smart Carriers for Controlled Drug Delivery via Ophthalmic Route. Drug Delivery Letters. 2025 Dec, 15(4): 427-48.
  22. D’Souza A, Pissurlenkar RR. Design and development of nanoparticle-loaded in-situ gel for enhanced and sustained ophthalmic delivery. Drug Delivery Letters, 2025 Jun; 15(2): 145-62.
  23. Patel N, Raval AM. Gastro-retentive drug delivery system: A review. Int J Pharm Sci., 2026; 4(1): 734-42.
  24. Raval AM, Bhavsar PR, Pandya FU, Patel D. Co-processed excipients in pharmaceutical formulation: advances, characterization, and applications. Asian Journal of Pharmaceutical Research and Development, 2026 Feb 16, 14(01): 105-3.
  25. Devi S, Saini V, Mehan N, Kumar M, Mujtaba MA, Elhassan GO, Haider N, Warsi MH. Development and Evaluation of Prednisolone Acetate-Loaded Nanostructured Lipid Carriers Integrated into pH-Triggered In Situ Gels for Ocular Drug Delivery. ASSAY and Drug Development Technologies, 2026 Jan 1; 24(1): 49-64.
  26. Pawar PK, Rathod RD, Jagdale MS. A review on topical ophthalmic drug delivery system: Reference to viscosity enhancer. Polymers in Medicine, 2024 Apr 5; 54(1): 10-7219.
  27. Pawar PK, Rathod RD, Jagdale MS. A review on topical ophthalmic drug delivery system: Reference to viscosity enhancer. Polymers in Medicine, 2024 Apr 5; 54(1): 10-7219.
  28. Tsung TH, Chen YH, Lu DW. Updates on biodegradable formulations for ocular drug delivery. Pharmaceutics, 2023 Feb 22; 15(3): 734.
  29. Thakor AD, Dharajiya RM, Shaikh MZ, Raval AM. A review on neuropharmacology: mechanisms, drug classes, and clinical applications. Asian Journal of Pharmaceutical Research and Development, 2026 Feb 15; 14(01): 114-21.
  30. Falwariya R, Jethva T, Raval AM, Lokhande D. Comprehensive review: Microneedle patches-A painless revolution in transdermal drug delivery. World J Pharm Med Res, 2026; 12(1): 199-207.
  31. Kale SS, Kulkarni D, Magar AG, Butle SR, Chalikwar SS, Moravkar KK. SeDeM and Powder flow tools-assisted design of solid SMEDDS of luliconazole for antifungal therapy. Therapeutic Delivery, 2026 Jan 2; 17(1): 39-52.
  32. Kushkiwala AM, Zankhwala FM, Patel MD, Raval AM. Flurbiprofen loaded Ethosomal gel: Design, optimization, and anti-inflammatory activity. International Journal of Research and Analytical Reviews, 2024; 11(4): 709-20.
  33. Dokania S, Joshi AK. Self-microemulsifying drug delivery system (SMEDDS)-challenges and road ahead. Drug delivery, 2015 Aug 18; 22(6): 675-90.
  34. Rahman MA, Hussain A, Hussain MS, Mirza MA, Iqbal Z. Role of excipients in successful development of self-emulsifying/microemulsifying drug delivery system (SEDDS/SMEDDS). Drug development and industrial pharmacy, 2013 Jan 1; 39(1): 1-9.
  35. Liu C, Guo L, Chen L, Gong X, Han Z, Feng J, Zhang C, Wu S, Yang Q. Development and Evaluation of a Phospholipid Complex-Loaded SMEDDS for Enhanced Oral Delivery of H007, a Novel Anti-Hyperlipidemic Drug. Pharmaceutics, 2026 Apr 13; 18(4): 474.

Document Actions

Full Article Download
Article views: 35

Citation

Sheeshpalsinh Solanki, Jaini K. Patel, Amar M. Raval, Dr. Disha Suthar, Priyanka Yadav (2026). Development and Characterization of a SMEDDS-Based in Situ Ophthalmic Drug Delivery System for Nepafenac. International Journal of Advanced Pharmaceutical and Healthcare, 1(3), 01–09.

DOI: https://doi.org/10.5281/zenodo.23344977

Copyright © Creative Commons Attribution 4.0 (CC BY 4.0)

© 2026 International Journal of Advanced Pharmaceutical and Healthcare (IJAPH). All rights reserved. | Licensed under Creative Commons Attribution 4.0 (CC BY 4.0)