Development and Characterization of Lornoxicam-Infused Ocular Gel for Effective Treatment of Ocular Inflammation in Domestic Cats
Main Article Content
Abstract
Lornoxicam (LOX) is a non-steroidal anti-inflammatory drug (NSAID) effective in managing ocular inflammation. Traditional delivery methods like liquid drops are cleared rapidly and may not provide sustained therapeutic levels, necessitating the development of an ocular gel formulation. Mucoadhesive polymers such as hyaluronic acid (HA), hydroxypropyl methylcellulose (HPMC), and Carbopol have been identified as suitable excipients to modify drug release profiles. This study aims to formulate an effective ophthalmic 0.1% w/w lornoxicam gel administered to pets for topical and continuous drug release, enhancing therapeutic efficacy while minimizing possible side effects. Eight formulations of lornoxicam ocular gel were developed by different concentrations of hyaluronic acid (HA) and hydroxypropyl methylcellulose (HPMC K100) with 0.5% w/v Carbopol P934. These formulations were in vitro evaluated for viscosity, spreadability, and drug release characteristics to the best formula G6. The formulation with optimal performance was G6 (0.5% w/v Hyaluronic acid). Ocular irritation testing was performed to assess the safety and tolerability of the formulation using a Rattus norvegicus Domestica (domestic Norwegian rat) model. Furthermore, the therapeutic potential of the lornoxicam gel was investigated in a domestic cat case study, demonstrating its efficacy in treating ocular inflammation resulting from traumatic eye injury. The optimized formula G6 formulation 0.5% w/v demonstrated appropriate viscosity and spreadability, making it suitable for ocular administration. In vitro release, studies revealed an initial burst release of 92.5% within the first two hours, followed by a sustained release over the subsequent 6 hours. Ocular irritation testing using a rat model confirmed that the lornoxicam ocular gel was non-irritating. Furthermore, the therapeutic effects of the gel were observed in domestic cats, with notable improvements in ocular conditions, including reduced swelling, redness, and dryness, for less than 7 days of treatment. The lornoxicam ocular gel demonstrates promising characteristics for safe and effective treatment of ocular inflammation in domestic cats.
Received: 08 November2024
Revised: 01 December 2024
Accepted: 21 January 2025
Published: 28 June 2025
Downloads
Article Details
How to Cite
References
1. Alkwak RSY, Rajab NA. Lornoxicam-loaded cubosomes: Preparation and in vitro characterization. Iraqi J Pharm Sci. 2022;31(1):144-153. https://doi.org/10.31351/vol31iss1pp144-153
2. Jassim ZE, Mohammed MF, Sadeq ZA. Formulation and evaluation of fast dissolving film of lornoxicam. Asian J Pharm Clin Res. 2018;11(9):217-223. https://doi.org/10.22159/ajpcr.2018.v11i9.27098
3. Verma NK, Singh AK, Mall PC, Yadav V. Identification and characterization of lornoxicam (non-steroidal anti-inflammatory drug). Int J Phar Clin Res. 2019;1(2):01-3. https://doi.org/10.33545/26647591.2019.v1.i2a.7
4. Shafiq M, Khan BA, Rashid SA, Khan MK, Naseem F, Alqahtani AM, et al. Biodegradable Polymeric Pharmaceutical Nanoemul gel Coloaded with Eucalyptol-Lornoxicam: Fabrication and Characterizations for Possible Better Pain Management. BioMed Res Int. 2023;2023(1):4227242. https://doi.org/10.1155/2023/4227242
5. Fatima K, Bukhari NI, Latif S, Afzal H, Hussain A, Shamim R, et al. Amelioration of physicochemical, pharmaceutical, and pharmacokinetic properties of lornoxicam by cocrystallization with a novel coformer. Drug DevIndPharm.2021;47(3):498-508. https://doi.org/10.1080/03639045.2021.1892744
6. Yin J, Huang Z, Wu B, Shi Y, Cao C, Lu Y. Lornoxicam protects mouse cornea from UVB-induced damage via inhibition of NF-κB activation. Br J Ophthalmol. 2008;92(4):562-568. https://doi.org/10.1136/bjo.2007.129064
7. Hashmat D, Shoaib MH, Ali FR, Siddiqui F. Lornoxicam controlled release transdermal gel patch: Design, characterization and optimization using co-solvents as penetration enhancers. PLoSOne. 2020;15(2):1-23. https://doi.org/10.1371/journal.pone.0228908
8. Polat HK, Ünal S, Aytekin E, Karakuyu NF, Haydar MK, Kurt N, et al. Formulation development of Lornoxicam loaded heat triggered ocular in-situ gel using factorial design. Drug Dev Ind Pharm. 2023;49(9):601-615. https://doi.org/10.1080/03639045.2023.2264932
9. Hsu KK, Pinard CL, Johnson RJ, Allen DG, Kukanich BK, Nykamp SG. Systemic absorption and adverse ocular and systemic effects after topical ophthalmic administration of 0.1% diclofenac to healthy cats. Am J Vet Res. 2015;76(3):253-565. https://doi.org/10.2460/ajvr.76.3.253
10. Alkhiro AR, Ghareeb MM. Formulation and evaluation of lornoxicam as dissolving microneedle patch. Iraqi J Pharm Sci. 2020;29(1):184-194. https://doi.org/10.31351/vol29iss1pp184-194
11. Hosmani AH, Patil ND, Pawar AA, Honmane SM. Development and evaluation of fenofibrate surface solid dispersion for improved solubility and dissolution rate. Ind. J. Pharm. Edu. Res. 2024;58(2):446-452. https://doi.org/10.5530/ijper.58.2.50
12. Dawood BY, Kassab HJ. Preparation and in vitro evaluation of naproxen as a pH sensitive ocular insitu gel. Int J Appl Pharm. 2019;11(2):37-44. https://doi.org/10.22159/ijap.2019v11i2.31229
13. Salunke SR, Patil SB. Ion activated in situ gel of gellan gum containing salbutamol sulphate for nasal administration. Int J Biol Micromole. 2016; 87:41-7. https://doi.org/10.1016/j.ijbiomac.2016.02.044
14. Kumar P, Rawat M, Thakur H, Pharmacy DOF. Formulation and Evaluation of Ocular in Situ Gelling Systems of Ciprofloxacin Hydrochloride. Int J Res Anal Rev.2024;11(2). https://www.ijrar.org/papers/IJRARTH00232.pdf
15. Agibayeva LE, Kaldybekov DB, and Porfiryeva NN, et al. Gellan gum and its methacrylate derivatives as in situ gelling mucoadhesive formulations of pilocarpine: In vitro and in vivo studies. Int J Pharm. 2020;577. https://doi.org/10.1016/j.ijpharm.2020.119093
16. Neama JM J, Al- Akkam E. Characterization and animal skin irritations investigation of vemurafenib microemulsion-based hydrogel using oily ionic liquid. Iraqi J Vet Med. 2024;48(1):81-92. https://doi.org/10.30539/8z83dp63
17. Bao Q, Jog R, Shen J, Newman B, Wang Y, Choi S, et al. Physicochemical attributes and dissolution testing of ophthalmic ointments. Int J Pharm. 2017;523(1):310-319. https://doi.org/10.1016/j.ijpharm.2017.03.039
18. Thombre NA, Niphade PS, D. Ahire E, J. Kshirsagar S. Formulation development and evaluation of microemulsion based lornoxicam gel. Biosci Biotechnol Res Asia. 2022;19(1):69-80. https://doi.org/10.13005/bbra/2968
19. Jin CJ, Yu SH, Wang XM, Woo SJ, Park HJ, Lee HC, et al. The effect of lithospermic acid, an antioxidant, on development of diabetic retinopathy in spontaneously obese diabetic rats. PLoS One. 2014;9(6). https://doi.org/10.1371/journal.pone.0098232
20. Anumolu PD, Sunitha G, Bindu SH, Satheshbabu PR, Subrahmanyam CVS. Development and validation of discriminating and biorelevant dissolution test for lornoxicam tablets. Indian J Pharm Sci. 2015;77(3):312-20. https://doi.org/10.4103/0250-474X.159653
21. Xie F, Ji S, Cheng Z. In vitro dissolution similarity factor (f2) and in vivo bioequivalence criteria, how and when do they match? Using a BCS class II drug as a simulation example. Eur J Pharm Sci. 2015;66:163-172. https://doi.org/10.1016/j.ejps.2014.10.002
22. OECD. Test Guideline No. 405: Acute Eye Irritation/Corrosion. 2023; 405. https://www.oecd.org/en/publications/2023/07/test-no-405-acute-eye-irritation-corrosion_g1g24072.html
23. Krakowian D, Gądarowska D, Daniel-Wójcik A, Mrzyk I. A proposal for a new in vitro method for direct classification of eye irritants by cytotoxicity test Preliminary study. Toxicol Lett. 202;338:58-66. https://doi.org/10.1016/j.toxlet.2020.12.003
24. Krishnatreyya H, Hazarika H, Saha A, Chattopadhyay P. Fundamental pharmacological expressions on ocular exposure to capsaicin, the principal constituent in pepper sprays. Sci Rep. 2018;8(1):1-18. https://doi.org/10.1038/s41598-018-30542-2
25. Eaton JS, Miller PE, Bentley E, Thomasy SM, Murphy CJ. The SPOTS System: An Ocular Scoring System Optimized for Use in Modern Preclinical Drug Development and Toxicology. J Ocul Pharmacol Ther. 2017;33(10):718-734. https://doi.org/10.1089/jop.2017.0108
26. Budai L, Budai M, Fülöpné Pápay ZE, Vilimi Z, Antal I. Rheological considerations of pharmaceutical formulations: Focus on viscoelasticity. Gels. 2023;9(6). https://doi.org/10.3390/gels9060469
27. Jassim BM, Al-Khedairy EBH. Formulation and in vitro/in vivo evaluation of silymarin solid dispersion-based topical gel for wound healing. Iraqi J Pharm Sci. 2023;32:42-53. https://doi.org/10.31351/vol32issSuppl.pp42-53
28. Pawar PK, Rathod RD, Jagadale SR. A review on topical ophthalmic drug delivery system: Reference to viscosity enhancer. Polim Med. 2024;54(1):71-84. https://doi.org/10.17219/pim/166413
29. Sunitha R, Venugopal K, Satyanarayana SV. Design, development, and evaluation of controlled release tablets of Nateglinide solid dispersions. Asian J Pharm. 2021;15(1):115-123. https://doi.org/10.22377/ajp.v15i1.3610
30. Kaluzhny Y, Klausner M. In vitro reconstructed 3D corneal tissue models for ocular toxicology and ophthalmic drug development. Vitr Cell Dev Biol - Anim. 2021;57(2):207-237. https://doi.org/10.1007/s11626-020-00533-7
31. Ross A, Willson VL. One-Way Anova. In: Basic and Advanced Statistical Tests. Rotterdam: SensePublishers; 2017. p. 21–24. https://doi.org/10.1007/978-94-6351-086-8_5
32. Zewail MB, Asaad GF, Swellam SM, El-Hamid MA, El-Khordagui LK, Sallah SK, et al. Design, characterization and in vivo performance of solid lipid nanoparticles (SLNs)-loaded mucoadhesive buccal tablets for efficient delivery of Lornoxicam in experimental inflammation. Int J Pharm. 2022;624:122006. https://doi.org/10.1016/j.ijpharm.2022.122006