Skip to content
2000
Volume 15, Issue 2
  • ISSN: 2210-3031
  • E-ISSN: 2210-304X

Abstract

Background

Flurbiprofen, a non-selective COX inhibitor utilized for managing mild to moderate pain and inflammation, operates through reversible inhibition of both COX-1 and COX-2 pathways. However, as a BCS class II drug, it exhibits limited aqueous solubility, leading to suboptimal ocular bioavailability and a brief corneal contact.

Objectives

The goal of this study was to amplify the aqueous solubility of Flurbiprofen by formulating it into a nanosuspension, which was subsequently incorporated into an gelling system so as to extend the ocular residence time and to achieve sustained drug release.

Methods

Nanosuspensions were crafted through the anti-solvent precipitation ultra-sonication method. The assessment included parameters, such as particle size, surface morphology, XRD, and FT-IR. The optimized nanosuspension was then incorporated into a pH-sensitive gel.

Results

The developed formulation was stable and showed enhanced contact time, minimizing the frequency of administration. Morphological analysis unveiled spherical drug nanoparticles in the nanosuspension without any signs of aggregation, supported by high-resolution transmission electron microscopy. The permeation studies showed a drug release of 83.48%, indicating good permeation and histopathology, and isotonicity indicated no ocular irritation and tissue damage.

Conclusion

The design and development of Flurbiprofen nanosuspension were found to be liquid at the formulated pH and formed gel due to changes in bonds between polymers. ocular gels minimize the risk of systemic absorption of the drug, as they are designed to stay localized on the ocular surface and within the eye. An optimum point can be reached in the shortest time with minimum efforts to achieve desirable rheological and release properties for gelling systems.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/ddl/10.2174/0122103031315270241120053529
2024-12-13
2025-09-13

  • From This Site

    /content/journals/ddl/10.2174/0122103031315270241120053529
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. RudrarajuM. NarayananS.P. SomanathP.R. Regulation of blood-retinal barrier cell-junctions in diabetic retinopathy.Pharmacol. Res.202016110511510.1016/j.phrs.2020.10511532750417
     [Google Scholar]
  2. AkhterM.H. AhmadI. AlshahraniM.Y. Al-HarbiA.I. KhalilullahH. AfzalO. AltamimiA.S.A. Najib UllahS.N.M. OjhaA. KarimS. Drug delivery challenges and current progress in nanocarrier-based ocular therapeutic system.Gels2022828210.3390/gels802008235200463
     [Google Scholar]
  3. SubriziA. del AmoE.M. Korzhikov-VlakhV. TennikovaT. RuponenM. UrttiA. Design principles of ocular drug delivery systems: importance of drug payload, release rate, and material properties.Drug Discov. Today20192481446145710.1016/j.drudis.2019.02.00130738982
     [Google Scholar]
  4. ShahM.R. ImranM. UllahS. Overcoming ocular barriers through nanocarrier-based drug delivery systems.Nanocarriers for Organ-Specific and Localized Drug Delivery.Elsevier202222524410.1016/B978‑0‑12‑821093‑2.00009‑8
     [Google Scholar]
  5. WengY. LiuJ. JinS. GuoW. LiangX. HuZ. Nanotechnology-based strategies for treatment of ocular disease.Acta Pharm. Sin. B20177328129110.1016/j.apsb.2016.09.00128540165
     [Google Scholar]
  6. (a) MofidfarM. AbdiB. AhadianS. MostafaviE. DesaiT.A. AbbasiF. SunY. MancheE.E. TaC.N. FlowersC.W. Drug delivery to the anterior segment of the eye: A review of current and future treatment strategies.Int. J. Pharm.202160712092410.1016/j.ijpharm.2021.12092434324989
     [Google Scholar]
  7. (a) MofidfarM. AbdiB. AhadianS. MostafaviE. DesaiT.A. AbbasiF. SunY. MancheE.E. TaC.N. FlowersC.W. Drug delivery to the anterior segment of the eye: A review of current and future treatment strategies.Int. J. Pharm.202160712092410.1016/j.ijpharm.2021.12092434324989
     [Google Scholar]
  8. KhandbahaleS.V. A Review-Nanosuspension Technology in Drug Delivery System.Asian Journal of Pharmaceutical Research20199213010.5958/2231‑5691.2019.00021.2
     [Google Scholar]
  9. GuptaS. KesarlaR. OmriA. Formulation strategies to improve the bioavailability of poorly absorbed drugs with special emphasis on self-emulsifying systems.ISRN Pharm.2013201311610.1155/2013/84804324459591
     [Google Scholar]
  10. SalawiA. Self-emulsifying drug delivery systems: a novel approach to deliver drugs.Drug Deliv.20222911811182310.1080/10717544.2022.208372435666090
     [Google Scholar]
  11. YadollahiR. VasilevK. SimovicS. Nanosuspension Technologies for Delivery of Poorly Soluble Drugs.J. Nanomater.20152015121637510.1155/2015/216375
     [Google Scholar]
  12. PurkayasthaH.D. HossianS.K.I. NANOSUSPENSION: A MODERN TECHNOLOGY USED IN DRUG DELIVERY SYSTEM.Int. J. Curr. Pharm. Res.20191–31310.22159/ijcpr.2019v11i3.34098
     [Google Scholar]
  13. MakwanaS.B. PatelV.A. ParmarS.J. Development and characterization of in-situ gel for ophthalmic formulation containing ciprofloxacin hydrochloride.Results Pharma Sci.201661610.1016/j.rinphs.2015.06.00126949596
     [Google Scholar]
  14. AshishB. Ashish B. Budhrani Kirti G. Sahu Sukeshini B. Lote Manish P. Deshmukh Sagar B. Wankhede Deepak S. Khobragade Nanosuspension: A Modern Approach In Drug Delivery System- A Review.International Journal of Research in Pharmaceutical Sciences202011SPL41526153010.26452/ijrps.v11iSPL4.4333
     [Google Scholar]
  15. KocbekP. BaumgartnerS. KristlJ. Preparation and evaluation of nanosuspensions for enhancing the dissolution of poorly soluble drugs.Int. J. Pharm.20063121-217918610.1016/j.ijpharm.2006.01.00816469459
     [Google Scholar]
  16. SeyfoddinA. ShawJ. Al-KassasR. Solid lipid nanoparticles for ocular drug delivery.Drug Deliv.201017746748910.3109/10717544.2010.48325720491540
     [Google Scholar]
  17. DasankoppaF. KujurS. Ahmed SholapurH.N. JamakandiV. Design, formulation and evaluation of carboxy methyl tamarind based in situ gelling ophthalmic drug delivery system of dorzolamide hydrochloride.Indian Journal of Health Sciences and Biomedical Research (KLEU)20169156[KLEU].10.4103/2349‑5006.183688
     [Google Scholar]
  18. NoureenS. NoreenS. GhummanS.A. AbdelrahmanE.A. BatoolF. AslamA. MehdiM. ShirinfarB. AhmedN. A novel pH-responsive hydrogel system based on Prunus armeniaca gum and acrylic acid: Preparation and evaluation as a potential candidate for controlled drug delivery.Eur. J. Pharm. Sci.202318910655510.1016/j.ejps.2023.10655537543064
     [Google Scholar]
  19. HanagandiV. Sidagouda PatilA. MasareddyR.S. DandagiP.M. BolmalU.B. Development and Evaluation of Nanosuspension Incorporated in situ gel of Brimonidine Tartarate for Ocular Drug Delivery.Indian Journal of Pharmaceutical Education and Research20225619410210.5530/ijper.56.1.12
     [Google Scholar]
  20. PaulS. MajumdarS. ChakrabortyM. Revolutionizing ocular drug delivery: recent advancements in in situ gel technology.Bull. Natl. Res. Cent.202347115410.1186/s42269‑023‑01123‑9
     [Google Scholar]
  21. DubashynskayaN. PoshinaD. RaikS. UrttiA. SkorikY.A. Polysaccharides in Ocular Drug Delivery.Pharmaceutics20191212210.3390/pharmaceutics1201002231878298
     [Google Scholar]
  22. KarkiS. KimH. NaS.J. ShinD. JoK. LeeJ. Thin films as an emerging platform for drug delivery.Asian Journal of Pharmaceutical Sciences201611555957410.1016/j.ajps.2016.05.004
     [Google Scholar]
  23. TanejaS. ShilpiS. KhatriK. Formulation and optimization of efavirenz nanosuspensions using the precipitation-ultrasonication technique for solubility enhancement.Artif. Cells Nanomed. Biotechnol.20151710.3109/21691401.2015.100850525724312
     [Google Scholar]
  24. KhuranaL.K. SinghR. SinghH. SharmaM. Systematic Development and Optimization of an in-situ Gelling System for Moxifloxacin Ocular Nanosuspension using High-pressure Homogenization with an Improved Encapsulation Efficiency.Curr. Pharm. Des.201824131434144510.2174/138161282466618040311510629611480
     [Google Scholar]
  25. KolawoleO.M. CookM.T. In situ gelling drug delivery systems for topical drug delivery.Eur. J. Pharm. Biopharm.2023184364910.1016/j.ejpb.2023.01.00736642283
     [Google Scholar]
  26. HimawanA. DjideN.J.N. MardikasariS.A. UtamiR.N. ArjunaA. DonnellyR.F. PermanaA.D. A novel in vitro approach to investigate the effect of food intake on release profile of valsartan in solid dispersion-floating gel in-situ delivery system.Eur. J. Pharm. Sci.202216810605710.1016/j.ejps.2021.10605734743031
     [Google Scholar]
  27. MaddiboyinaB. JhawatV. DesuP.K. GandhiS. NakkalaR.K. SinghS. Formulation and evaluation of thermosensitive flurbiprofen in situ nano gel for the ocular delivery.J. Biomater. Sci. Polym. Ed.202132121584159710.1080/09205063.2021.192746033977874
     [Google Scholar]
  28. FosterC. VitaleA. Al-DhibiH. Nonsteroidal Anti-inflammatory Drugs.StatPearlsTreasure Island (FL)StatPearls Publishing201310.5005/jp/books/11822_11
     [Google Scholar]
  29. BoddedaB. BodduP. AvasaralaH. JayantiV. Design and Ocular Tolerance of Flurbiprofen Loaded Nanosuspension.Pharm. Nanotechnol.201531566710.2174/2211738503666150630185230
     [Google Scholar]
  30. PignatelloR. BucoloC. SpedalieriG. MalteseA. PuglisiG. Flurbiprofen-loaded acrylate polymer nanosuspensions for ophthalmic application.Biomaterials200223153247325510.1016/S0142‑9612(02)00080‑712102196
     [Google Scholar]
  31. KesharwaniD. Das PaulS. PaliwalR. SatapathyT. Development, QbD based optimization and in vitro characterization of Diacerein loaded nanostructured lipid carriers for topical applications.Journal of Radiation Research and Applied Sciences202316210056510.1016/j.jrras.2023.100565
     [Google Scholar]
  32. ParekhH.B. JivaniR. JivaniN.P. PatelL.D. MakwanaA. SamejaK. NOVEL INSITU POLYMERIC DRUG DELIVERY SYSTEM: A REVIEW.J. Drug Deliv. Ther.20122510.22270/jddt.v2i5.276
     [Google Scholar]
  33. SingareD.S. MarellaS. GowthamrajanK. KulkarniG.T. VooturiR. RaoP.S. Optimization of formulation and process variable of nanosuspension: An industrial perspective.Int. J. Pharm.20104021-221322010.1016/j.ijpharm.2010.09.04120933066
     [Google Scholar]
  34. SharmaD.K. PattnaikG. BeheraA. Development and in-vitro, in-vivo evaluation of Pioglitazone-loaded polymeric nanoparticles using central composite design surface response methodology.OpenNano20231110014110.1016/j.onano.2023.100141
     [Google Scholar]
  35. DwiastutiR. SuhendraP.A. YulianiS.H. OctaF.D.R. Application of the central composite design approach for optimization of the nanosilver formula using a natural bioreductor from Camellia sinensis L. extract.J. Appl. Pharm. Sci.2022485610.7324/JAPS.2022.120806
     [Google Scholar]
  36. BhattacharyaS. Central composite design for response surface methodology and its application in pharmacy.Response Surface Methodology in Engineering ScienceIntechOpen202110.5772/intechopen.95835
     [Google Scholar]
  37. NjokuN. Application of central composite design with design expert v13 in process optimization.Response Surface Methodology - Research Advances and ApplicationsIntechOpen202310.5772/intechopen.109704
     [Google Scholar]
  38. BhargavE. Chaithanya BarghavG. Padmanabha ReddyY. Pavan kumarC. RamalingamP. HaranathC. A Design of Experiment (DoE) based approach for development and optimization of nanosuspensions of telmisartan, a BCS class II antihypertensive drug.Future Journal of Pharmaceutical Sciences2020611410.1186/s43094‑020‑00032‑2
     [Google Scholar]
  39. HaoJ. GaoY. ZhaoJ. ZhangJ. LiQ. ZhaoZ. LiuJ. Preparation and optimization of resveratrol nanosuspensions by antisolvent precipitation using Box-Behnken design.AAPS PharmSciTech201516111812810.1208/s12249‑014‑0211‑y25209687
     [Google Scholar]
  40. LiuZ. YangL. Antisolvent precipitation for the preparation of high polymeric procyanidin nanoparticles under ultrasonication and evaluation of their antioxidant activity in vitro.Ultrason. Sonochem.20184320821810.1016/j.ultsonch.2018.01.01929555277
     [Google Scholar]
  41. NanakiS. EleftheriouR.M. BarmpalexisP. KostoglouM. KaravasE. BikiarisD. Evaluation of Dissolution Enhancement of Aprepitant Drug in Ternary Pharmaceutical Solid Dispersions with Soluplus® and Poloxamer 188 Prepared by Melt Mixing.Sci2019124810.3390/sci1020048
     [Google Scholar]
  42. JakubowskaE. MilanowskiB. LulekJ. A Systematic Approach to the Development of Cilostazol Nanosuspension by Liquid Antisolvent Precipitation (LASP) and Its Combination with Ultrasound.Int. J. Mol. Sci.202122221240610.3390/ijms22221240634830298
     [Google Scholar]
  43. TeanmetawongS. ChantaramaneeT. LhosupasiriratS. WongariyakaweeA. SrikhirinT. A Comparison Study of Magnetic Stirrer and Sonicator Technique to Disperse 1% Span20 Treated Layered Double Hydroxides (LDHs).IOP Conf. Ser. Mater. Sci. Eng.201910.1088/1757‑899X/654/1/012005
     [Google Scholar]
  44. KumarS. HaglundB.O. HimmelsteinK.J. In Situ -Forming Gels for Ophthalmic Drug Delivery.J. Ocul. Pharmacol. Ther.1994101475610.1089/jop.1994.10.47
     [Google Scholar]
  45. PatelN. ThakkarV. MetaliaV. BaldaniyaL. GandhiT. GohelM. Formulation and development of ophthalmic in situ gel for the treatment ocular inflammation and infection using application of quality by design concept.Drug Dev. Ind. Pharm.20164291406142310.3109/03639045.2015.113730626716613
     [Google Scholar]
  46. MittalN. KaurG. In situ gelling ophthalmic drug delivery system: Formulation and evaluation.J. Appl. Polym. Sci.20141312app.3978810.1002/app.39788
     [Google Scholar]
  47. SopyanI. Design-expert software (doe): An application tool for optimization in pharmaceutical preparations formulation.Int. J. Appl. Pharmaceut.20222022556310.22159/ijap.2022v14i4.45144
     [Google Scholar]
  48. DwibediV. RathS.K. PrakashR. SaxenaS. Response surface statistical optimization of fermentation parameters for resveratrol production by the endophytic fungus Arcopilus aureus and its tyrosinase inhibitory activity.Biotechnol. Lett.202143362764410.1007/s10529‑020‑03032‑733159246
     [Google Scholar]
  49. ShelleyH. Rodriguez-GalarzaR.M. DuranS.H. AbarcaE.M. BabuR.J. In Situ Gel Formulation for Enhanced Ocular Delivery of Nepafenac.J. Pharm. Sci.2018107123089309710.1016/j.xphs.2018.08.01330170009
     [Google Scholar]
  50. ShirodkarS. PissurlenkarR. Formulation and Characterisation of Cilnidipine Microsponge Loaded Hydrogels for Antihypertensive Activity.Drug Deliv. Lett.2023131486810.2174/2210303113666221207142644
     [Google Scholar]
  51. AmmarH.O. SalamaH.A. GhorabM. MahmoudA.A. Development of dorzolamide hydrochloride in situ gel nanoemulsion for ocular delivery.Drug Dev. Ind. Pharm.201036111330133910.3109/0363904100380188520545523
     [Google Scholar]
  52. PANKAJ JADHAV ADHIKRAO YADAV Formulation, Optimization, and in vitro evaluation of polymeric nanosuspension of flurbiprofen.Asian J. Pharm. Clin. Res.201918319110.22159/ajpcr.2019.v12i11.35670
     [Google Scholar]
  53. SultanaA. ZareM. ThomasV. KumarT.S.S. RamakrishnaS. Nano-based drug delivery systems: Conventional drug delivery routes, recent developments and future prospects.Medicine in Drug Discovery20221510013410.1016/j.medidd.2022.100134
     [Google Scholar]
  54. AsasutjaritR. ThanasanchokpibullS. FuongfuchatA. VeeranondhaS. Optimization and evaluation of thermoresponsive diclofenac sodium ophthalmic in situ gels.Int. J. Pharm.20114111-212813510.1016/j.ijpharm.2011.03.05421459137
     [Google Scholar]
  55. KalariaV.J. SaisivamS. AlshishaniA. Aljariri AlhesanJ.S. ChakrabortyS. RahamathullaM. Design and evaluation of in situ gel eye drops containing nanoparticles of Gemifloxacin Mesylate.Drug Deliv.2023301218518010.1080/10717544.2023.218518036876464
     [Google Scholar]
  56. VyasU. GehalotN. JainV. MahajanS.C. A review on in situ gelling system for ophthalmic drug delivery.Current Research in Pharmaceutical Sciences20221149810610.24092/CRPS.2021.110402
     [Google Scholar]
  57. BalasingamR. KhanA. ThinakaranR. Formulation of in situ gelling system for ophthalmic delivery of erythromycin.Int. J. Stud. Res. Technol. Manage.201751810.18510/ijsrtm.2017.531
     [Google Scholar]
  58. EdsmanK. CarlforsJ. PeterssonR. Rheological evaluation of poloxamer as an in situ gel for ophthalmic use.Eur. J. Pharm. Sci.19986210511210.1016/S0928‑0987(97)00075‑49795025
     [Google Scholar]
  59. BonferoniM.C. RossiS. FerrariF. CaramellaC. A modified Franz diffusion cell for simultaneous assessment of drug release and washability of mucoadhesive gels.Pharm. Dev. Technol.199941455310.1080/1083745990898422310027212
     [Google Scholar]
  60. RanchK.M. MaulviF.A. NaikM.J. KoliA.R. ParikhR.K. ShahD.O. Optimization of a novel in situ gel for sustained ocular drug delivery using Box-Behnken design: In vitro, ex vivo, in vivo and human studies.Int. J. Pharm.201955426427510.1016/j.ijpharm.2018.11.01630423418
     [Google Scholar]
  61. GautamD. ChaurasiaH. SinghR. Design and optimization of lomefloxacin loaded NLC gel for ophthalmic drug delivery.Int. J. Health Sci.202220227022704410.53730/ijhs.v6nS3.7637
     [Google Scholar]
  62. UyM. TelfordJ.K. Optimization by Design of Experiment techniques.2009 IEEE Aerospace conference07-14 Mar, 2009, Big Sky, MT, USA, 2009, pp. 1-10.10.1109/AERO.2009.4839625
     [Google Scholar]
  63. WuH. LiuZ. PengJ. LiL. LiN. LiJ. PanH. Design and evaluation of baicalin-containing in situ pH-triggered gelling system for sustained ophthalmic drug delivery.Int. J. Pharm.20114101-2314010.1016/j.ijpharm.2011.03.00721397671
     [Google Scholar]
  64. CharooN.A. KohliK. AliA. Preparation of in situ-forming ophthalmic gels of ciprofloxacin hydrochloride for the treatment of bacterial conjunctivitis: in vitro and in vivo studies.J. Pharm. Sci.200392240741310.1002/jps.1029012532390
     [Google Scholar]
  65. AliF.M. Al-ShohaniA.D. Preparation and evaluation of in situ ophthalmic gel with a dual triggered mechanism for the delivery of gatifloxacin and betamethasone.Al-Rafidain J. Med. Sci.20246566310.54133/ajms.v6i2.597
     [Google Scholar]
  66. SenjotiF.G. TimminsP. ConwayB.R. SmithA.M. Optimizing ophthalmic delivery of a poorly water soluble drug from an aqueous in situ gelling system.Eur. J. Pharm. Biopharm.20201541710.1016/j.ejpb.2020.06.01632599271
     [Google Scholar]
  67. AhmedB. JaiswalS. NaryalS. ShahR.M. AlanyR.G. KaurI.P. In situ gelling systems for ocular drug delivery.J. Control. Release2024371678410.1016/j.jconrel.2024.05.03138768662
     [Google Scholar]
  68. AdısanoğluP. ÖzgüneyI. Development and characterization of thermosensitive and bioadhesive ophthalmic formulations containing flurbiprofen solid dispersions.Gels202410426710.3390/gels1004026738667685
     [Google Scholar]
/content/journals/ddl/10.2174/0122103031315270241120053529
Loading
Design and Development of Nanoparticle-loaded In-situ Gel for Enhanced and Sustained Ophthalmic Delivery
Drug Deliv Lett 15, 145 (2025); https://doi.org/10.2174/0122103031315270241120053529
/content/journals/ddl/10.2174/0122103031315270241120053529
/content/journals/ddl/10.2174/0122103031315270241120053529
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): anti-inflammatory; flurbiprofen; in-situ gel; Nanosuspension; ophthalmic drug delivery; poloxamer; sustained ocular release

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test