IN SITU GELLING OCULAR FILMS OF LORATADINE: A MUCOADHESIVE PLATFORM FOR ENHANCED ANTIHISTAMINIC OCULAR DELIVERY
DOI:
https://doi.org/10.22159/ijap.2026v18i2.56656Keywords:
Loratadine, Ocular drug delivery, In situ gelling film, Solvent casting method, Sustained release, Mucoadhesive filmAbstract
Objective: The objective of this study was to prepare an in situ gelling, mucoadhesive ocular film of loratadine, with extended precorneal retention and sustained release.
Methods: The films were formulated using the solvent casting method, using hydroxypropyl methylcellulose K4M (HPMC K4M) as a film-forming polymer, sodium hyaluronate (SH), sodium alginate (SA), polyvinylpyrrolidone K30 (PVP K-30) as mucoadhesive polymers, and propylene glycol (PG) as a plasticizer.
Results: Among the fourteen formulations prepared (F1-F14), formula (F5), containing 1% HPMC K4M and 0.75% SA, exhibited high drug content (99.11±3.57 %), suitable pH (7.03±0.09), thickness (0.080±0.008 mm) and tensile strength (3.44±0.11 N/mm2). The film quickly hydrated to form a gel-like structure with proper mucoadhesion (4.436±0.09 N), and in vitro dissolution studies showed sustained drug release (99.43% over 12 h) that best fitted Korsmeyer–Peppas model, suggesting Fickian diffusion. The developed film showed no cytotoxicity or irritation to eyes in studies conducted on rabbits.
Conclusion: The optimized in situ gelling loratadine ocular film has desirable properties, and is promising for long-term topical ocular delivery of loratadine.
References
1. Rodrigues J, Kuruvilla ME, Vanijcharoenkarn K, Patel N, Hom MM, Wallace DV. The spectrum of allergic ocular diseases-2020. Ann Allergy Asthma Immunol. 2021;126(3):240-54. doi: 10.1016/j.anai.2020.11.016, PMID 33276116.
2. Rozi MF, Mohmad Sabere AS. Review on conventional and novel topical ocular drug delivery system. Journal of Pharmacy. 2021;1(1):19-26. doi: 10.31436/jop.v1i1.32.
3. Jumelle C, Gholizadeh S, Annabi N, Dana R. Advances and limitations of drug delivery systems formulated as eye drops. J Control Release. 2020;321:1-22. doi: 10.1016/j.jconrel.2020.01.057, PMID 32027938.
4. Dosmar E, Walsh J, Doyel M, Bussett K, Oladipupo A, Amer S. Targeting ocular drug delivery: an examination of local anatomy and current approaches. Bioengineering (Basel). 2022;9(1):41. doi: 10.3390/bioengineering9010041, PMID 35049750.
5. Pelusi L, Mandatori D, Mastropasqua L, Agnifili L, Allegretti M, Nubile M. Innovation in the development of synthetic and natural ocular drug delivery systems for eye diseases treatment: focusing on drug-loaded ocular inserts contacts and intraocular lenses. Pharmaceutics. 2023;15(2):625. doi: 10.3390/pharmaceutics15020625, PMID 36839947.
6. Van Nguyen K, Dang TK, Vu LT, Ha NT, Truong HD, Tran TH. Orodispersible film incorporating nanoparticulate loratadine for an enhanced oral bioavailability. J Pharm Investig. 2023;53(3):417-26. doi: 10.1007/s40005-023-00613-2.
7. Sharif Makhmalzadeh BS, Salimi A, Niroomand A. Loratadine-loaded thermoresponsive hydrogel: characterization and ex-vivo rabbit cornea permeability studies. Iran J Pharm Res. 2018;17(2):460-9. PMID 29881404.
8. Abd El AE GOA, Shams ME, Maria DN. Formulation and in vitro evaluation of loratadine ocuserts. RGUHS J Pharm Sci. 2013;3(4):62-8. doi: 10.13140/RG.2.1.2297.4887.
9. Abd El-Gawad AE, Soliman OA, Shams ME, Maria DN. Formulation and in vitro evaluation of loratadine gels for ophthalmic use. RGUHS J Pharm Sci. 2014;4(2):62-9. doi: 10.5530/rjps.2014.2.5.
10. Abdelmonem R, Al-Samadi IE, El Nashar RM, Jasti BR, El-Nabarawi MA. Fabrication of nanostructured lipid carriers ocugel for enhancing Loratadine used in treatment of COVID-19 related symptoms: statistical optimization in vitro ex-vivo, and in vivo studies evaluation. Drug Deliv. 2022;29(1):2868-82. doi: 10.1080/10717544.2022.2115164, PMID 36065090.
11. Nyamweya NN. Applications of polymer blends in drug delivery. Futur J Pharm Sci. 2021;7(1):18. doi: 10.1186/s43094-020-00167-2.
12. Tundisi LL, Mostaco GB, Carricondo PC, Petri DF. Hydroxypropyl methylcellulose: physicochemical properties and ocular drug delivery formulations. Eur J Pharm Sci. 2021;159:105736. doi: 10.1016/j.ejps.2021.105736, PMID 33516807.
13. Ibrahim AG, Thomas LM. Formulation and evaluation of bilastine thermosensitive mucoadhesive ophthalmic in situ gel. Al-Rafidain J Med Sci. 2024;7(1):1-7. doi: 10.54133/ajms.v7i1.1014.
14. Al-Saedi ZH, Alzhrani RM, Boddu SH. Formulation and in vitro evaluation of cyclosporine-a inserts prepared using hydroxypropyl methylcellulose for treating dry eye disease. J Ocul Pharmacol Ther. 2016;32(7):451-62. doi: 10.1089/jop.2016.0013, PMID 27294697.
15. Ghadermazi R, Hamdipour S, Sadeghi K, Ghadermazi R, Khosrowshahi Asl A. Effect of various additives on the properties of the films and coatings derived from hydroxypropyl methylcellulose-a review. Food Sci Nutr. 2019;7(11):3363-77. doi: 10.1002/fsn3.1206, PMID 31762990.
16. Shukr M. Formulation in vitro and in vivo evaluation of lidocaine HCl ocular inserts for topical ocular Anesthesia. Arch Pharm Res. 2014;37(7):882-9. doi: 10.1007/s12272-013-0317-x, PMID 24395530.
17. Franco P, De Marco I. The use of poly(N-vinyl pyrrolidone) in the delivery of drugs: a review. Polymers. 2020;12(5):1114. doi: 10.3390/polym12051114, PMID 32414187.
18. Naga Priya KR, Bhattacharyya S, Ramesh Babu P. Formulation and evaluation of erodible ocular films of valacyclovir hydrochloride. Dhaka Univ J Pharm Sci. 2014;13(1):75-81. doi: 10.3329/dujps.v13i1.21866.
19. Huynh A, Priefer R. Hyaluronic acid applications in ophthalmology rheumatology and dermatology. Carbohydr Res. 2020;489:107950. doi: 10.1016/j.carres.2020.107950, PMID 32070808.
20. Hurtado A, Aljabali AA, Mishra V, Tambuwala MM, Serrano Aroca A. Alginate: enhancement strategies for advanced applications. Int J Mol Sci. 2022;23(9):4486. doi: 10.3390/ijms23094486, PMID 35562876.
21. Trastullo R, Abruzzo A, Saladini B, Gallucci MC, Cerchiara T, Luppi B. Design and evaluation of buccal films as paediatric dosage form for transmucosal delivery of ondansetron. Eur J Pharm Biopharm. 2016;105:115-21. doi: 10.1016/j.ejpb.2016.05.026, PMID 27267732.
22. Okeke OC, Boateng JS. Composite HPMC and sodium alginate-based buccal formulations for nicotine replacement therapy. Int J Biol Macromol. 2016;91:31-44. doi: 10.1016/j.ijbiomac.2016.05.079, PMID 27222284.
23. Khurana G, Arora S, Pawar PK. Ocular insert for sustained delivery of gatifloxacin sesquihydrate: preparation and evaluations. Int J Pharm Investig. 2012;2(2):70-7. doi: 10.4103/2230-973X.100040, PMID 23119235.
24. Jethava JK, Jethava GK. Design formulation and evaluation of novel sustained-release bioadhesive in-situ gelling ocular inserts of ketorolac tromethamine. Int J Pharm Investig. 2014;4(4):226-32. doi: 10.4103/2230-973X.143131, PMID 25426444.
25. Alwan ZS, Rajab NA. Preparation and characterization of febuxostat nanosuspension as a fast-dissolving oral film. Al-Rafidain J Med Sci. 2024;6(2):171-7. doi: 10.54133/ajms.v6i2.873.
26. Ghadhban HY, Ahmed KK. Nanosuspension-based repaglinide fast-dissolving buccal film for dissolution enhancement. AAPS PharmSciTech. 2024;25(6):161. doi: 10.1208/s12249-024-02868-w, PMID 38992175.
27. Wafa HG, Essa EA, El-Sisi AE, El Maghraby GM. Ocular films versus film-forming liquid systems for enhanced ocular drug delivery. Drug Deliv Transl Res. 2021;11(3):1084-95. doi: 10.1007/s13346-020-00825-1, PMID 32728811.
28. Radhi ZA, Ghareeb MM. Preparation and evaluation of rebamipide film using casting technique for local action. Iraqi J Pharm Sci. 2019;28(1):24-36. doi: 10.31351/vol28iss1pp24-36.
29. Kareem H, Rajab N. Formulation and characterization of eplerenone nanocrystal as sublingual fast-dissolving film. Iraqi J Pharm Sci. 2024;33(4):151-65. doi: 10.31351/vol33iss4pp151-165.
30. Alhamhoom Y, Said AK, Kumar A, Nanjappa SH, Wali D, Rahamathulla M. Sublingual fast-dissolving thin films of loratadine: characterization in vitro and ex vivo evaluation. Polymers. 2024;16(20):2919. doi: 10.3390/polym16202919, PMID 39458747.
31. Hermans K, Van Den Plas D, Kerimova S, Carleer R, Adriaensens P, Weyenberg W. Development and characterization of mucoadhesive chitosan films for ophthalmic delivery of cyclosporine a. Int J Pharm. 2014;472(1-2):10-9. doi: 10.1016/j.ijpharm.2014.06.017, PMID 24929014.
32. Aburahma MH, Mahmoud AA. Biodegradable ocular inserts for sustained delivery of brimonidine tartarate: preparation and in vitro/in vivo evaluation. AAPS PharmSciTech. 2011;12(4):1335-47. doi: 10.1208/s12249-011-9701-3, PMID 21979886.
33. Jovanovic M, Tomic N, Cvijic S, Stojanovic D, Ibric S, Uskokovic P. Mucoadhesive gelatin buccal films with propranolol hydrochloride: evaluation of mechanical mucoadhesive and biopharmaceutical properties. Pharmaceutics. 2021;13(2):273. doi: 10.3390/pharmaceutics13020273, PMID 33670448.
34. Abdelkader H, Pierscionek B, Alany RG. Novel in situ gelling ocular films for the opioid growth factor-receptor antagonist-naltrexone hydrochloride: fabrication mechanical properties mucoadhesion, tolerability and stability studies. Int J Pharm. 2014;477(1-2):631-42. doi: 10.1016/j.ijpharm.2014.10.069, PMID 25445974.
35. Sivadasan D, Venkatesan K, Mohamed JM, Alqahtani S, Asiri YI, Faisal MM. Application of 32 factorial design for loratadine-loaded nanosponge in topical gel formulation: comprehensive in vitro and ex vivo evaluations. Sci Rep. 2024;14(1):6361. doi: 10.1038/s41598-024-55953-2, PMID 38493177.
36. Costa P, Sousa Lobo JM. Modeling and comparison of dissolution profiles. Eur J Pharm Sci. 2001;13(2):123-33. doi: 10.1016/S0928-0987(01)00095-1, PMID 11297896.
37. Zhang Y, Huo M, Zhou J, Zou A, Li W, Yao C. DDSolver: an add-in program for modeling and comparison of drug dissolution profiles. AAPS J. 2010;12(3):263-71. doi: 10.1208/s12248-010-9185-1, PMID 20373062.
38. Shah P, Thakkar V, Anjana V, Christian J, Trivedi R, Patel K. Exploring of taguchi design in the optimization of brinzolamide and timolol maleate ophthalmic in-situ gel used in treatment of glaucoma. Curr Drug Ther. 2020;15(5):524-42. doi: 10.2174/1574885514666190916151506.
39. Hardia A. Preparation and evaluation of biodegradable ocular inserts of timolol maleate. IJPSM. 2021;6(3):21-38. doi: 10.47760/ijpsm.2021.v06i03.003.
40. Teba HE, Khalil IA, Gebreel RM, Fahmy LI, Sorogy HM. Development of antifungal fibrous ocular insert using the freeze-drying technique. Drug Deliv Transl Res. 2024;14(9):2520-38. doi: 10.1007/s13346-024-01527-8, PMID 38366116.
41. Jafer RS, J Kassab HJ. Development and characterization of lornoxicam-infused ocular gel for effective treatment of ocular inflammation in domestic cats. Iraqi J Vet Med. 2025;49(1):8-15. doi: 10.30539/pw6vsy73.
42. Fulgencio GdO, Viana FA, Ribeiro RR, Yoshida MI, Faraco AG, Cunha-Junior AdS. New mucoadhesive chitosan film for ophthalmic drug delivery of timolol maleate: in vivo evaluation. J Ocul Pharmacol Ther. 2012;28(4):350-8. doi: 10.1089/jop.2011.0174, PMID 22320419.
43. Mishra D, Gilhotra R. Design and characterization of bioadhesive in-situ gelling ocular inserts of gatifloxacin sesquihydrate. DARU J Pharm Sci. 2008;16(1):1-8.
44. Chughtai FR, Zaman M, Khan AH, Amjad MW, Aman W, Khan SM. Formulation and evaluation of sustained release ocular inserts of betaxolol hydrochloride using arabinoxylan from Plantago ovata. Pak J Pharm Sci. 2021;34(Suppl 3):S1069-74. doi: 10.36721/PJPS.2021.34.3.
45. British Pharmacopoeia Commission. London: the stationery office. Appendix XII C. Consistency of Formulated Preparations; 2023.
46. Nanda A, Das S, Sahoo RN, Nandi S, Swain R, Pattanaik S. Aspirin–hydrogel ocular film for topical delivery and ophthalmic anti-inflammation. J Serb Chem Soc. 2022;87(7-8):829-43. doi: 10.2298/JSC210504019N.
47. Dave V. Design and evaluation of aceclofenac ocular inserts with special reference to cataracts and conjunctivitis. J Chin Pharm Sci. 2013;22(5):449. doi: 10.5246/jcps.2013.05.066.
48. Noori MM, Al-Shohani AD, Yousif NZ. Fabrication and characterization of new combination ocular insert for the combined delivery of tinidazole and levofloxacin. Mater Today Proc. 2023;80:2652-9. doi: 10.1016/j.matpr.2021.07.008.
49. Ding C, Zhang M, Li G. Preparation and characterization of collagen/hydroxypropyl methylcellulose (HPMC) blend film. Carbohydr Polym. 2015;119:194-201. doi: 10.1016/j.carbpol.2014.11.057, PMID 25563960.
50. Wang Y, Jiang S, Chen Y, Qiu D, Weng Y. Synthesis and characterization of a novel composite edible film based on hydroxypropyl methyl cellulose grafted with gelatin. Gels. 2023;9(4):332. doi: 10.3390/gels9040332, PMID 37102944.
51. Kraisit P, Limmatvapirat S, Nunthanid J, Sriamornsak P, Luangtana Anan M. Preparation and characterization of hydroxypropyl methylcellulose/polycarbophil mucoadhesive blend films using a mixture design approach. Chem Pharm Bull (Tokyo). 2017;65(3):284-94. doi: 10.1248/cpb.c16-00849, PMID 27980251.
52. Salih SI, Jabur AR, Mohammed T, editors. The effect of PVP addition on the mechanical properties of ternary polymer blends. IOP Conf S Mater Sci Eng. 2018;433:012071. doi: 10.1088/1757-899X/433/1/012071.
53. Salih SI, Jabur AR, Mohammed T. The effect of PVP addition on the mechanical properties of ternary polymer blends. IOP Conf Ser: Mater Sci Eng. 2018;433:012071. doi: 10.1088/1757-899X/433/1/012071.
54. Jain D, Carvalho E, Banerjee R. Biodegradable hybrid polymeric membranes for ocular drug delivery. Acta Biomater. 2010;6(4):1370-9. doi: 10.1016/j.actbio.2009.11.001, PMID 19900594.
55. Ghosal K, Ranjan A, Bhowmik BB. A novel vaginal drug delivery system: anti-HIV bioadhesive film containing abacavir. J Mater Sci Mater Med. 2014;25(7):1679-89. doi: 10.1007/s10856-014-5204-6, PMID 24699799.
56. Wang Y, Zhang L, Liu H, Yu L, Simon GP, Zhang N. Relationship between morphologies and mechanical properties of hydroxypropyl methylcellulose/hydroxypropyl starch blends. Carbohydr Polym. 2016;153:329-35. doi: 10.1016/j.carbpol.2016.07.029, PMID 27561503.
57. Zhang L, Wang XF, Liu H, Yu L, Wang Y, Simon GP. Effect of plasticizers on microstructure compatibility and mechanical property of hydroxypropyl methylcellulose/hydroxypropyl starch blends. Int J Biol Macromol. 2018;119:141-8. doi: 10.1016/j.ijbiomac.2018.07.064, PMID 30016660.
58. Ravindran VK, Repala S, Subadhra S, Appapurapu AK. Chick chorioallantoic membrane model for in ovo evaluation of timolol maleate-brimonidine tartrate ocular inserts. Drug Deliv. 2014;21(4):307-14. doi: 10.3109/10717544.2013.845272, PMID 24134746.
59. Hernandez Gonzalez ME, Rodriguez Gonzalez CA, Valencia Gomez LE, Hernandez Paz JF, Jimenez Vega F, Salcedo M. Characterization of HPMC and PEG 400 mucoadhesive film loaded with retinyl palmitate and ketorolac for intravaginal administration. Int J Mol Sci. 2024;25(23):12692. doi: 10.3390/ijms252312692, PMID 39684402.
60. Tighsazzadeh M, Mitchell JC, Boateng JS. Development and evaluation of performance characteristics of timolol-loaded composite ocular films as potential delivery platforms for treatment of glaucoma. Int J Pharm. 2019;566:111-25. doi: 10.1016/j.ijpharm.2019.05.059, PMID 31129346.
61. Al-Mamari A, Shahitha F, Al-Sibani M, Al Saadi A, Al Harrasi A, Ahmad A. Novel antibacterial wound healing hydrogels based on HEC/SA/HA using green chemistry approach. Lett Appl Nanobiosci. 2023;12:69. doi: 10.1016/j.eurpolymj.2018.09.003.
62. Abou-Okeil A, Fahmy HM, El-Bisi MK, Ahmed-Farid OA. Hyaluronic acid/Na-alginate films as topical bioactive wound dressings. Eur Polym J. 2018;109:101-9. doi: 10.1016/j.eurpolymj.2018.09.003.
63. El Gamal SS, Naggar VF, Allam AN. Formulation and evaluation of acyclovir ophthalmic inserts. Asian J Pharm Sci. 2008;3(2):58-67.
64. Bayer IS. Recent advances in mucoadhesive interface materials, mucoadhesion characterization and technologies. Adv Materials Inter. 2022;9(18):2200211. doi: 10.1002/admi.202200211.
65. Nanda A, Sahoo RN, Pramanik A, Mohapatra R, Pradhan SK, Thirumurugan A. Drug-in-mucoadhesive type film for ocular anti-inflammatory potential of amlodipine: effect of sulphobutyl-ether-beta-cyclodextrin on permeation and molecular docking characterization. Colloids Surf B Biointerfaces. 2018;172:555-64. doi: 10.1016/j.colsurfb.2018.09.011, PMID 30218981.
66. Alzahrani A, Adel Ali Youssef AA, Senapati S, Tripathi S, Bandari S, Majumdar S. Formulation development and in vitro–ex vivo characterization of hot-melt extruded ciprofloxacin hydrochloride inserts for ocular applications: part I. Int J Pharm. 2023;630:122423. doi: 10.1016/j.ijpharm.2022.122423, PMID 36427695.
67. Pamlenyi K, Kristo K, Jojart Laczkovich O, Regdon G. Formulation and optimization of sodium alginate polymer film as a buccal mucoadhesive drug delivery system containing cetirizine dihydrochloride. Pharmaceutics. 2021;13(5):619. doi: 10.3390/pharmaceutics13050619, PMID 33925927.
68. Gilhotra RM, Gilhotra N, Mishra DN. Piroxicam bioadhesive ocular inserts: physicochemical characterization and evaluation in prostaglandin-induced inflammation. Curr Eye Res. 2009;34(12):1065-73. doi: 10.3109/02713680903340738, PMID 19958126.
69. Pan P, Svirskis D, Waterhouse GIN, Wu Z. Hydroxypropyl methylcellulose bioadhesive hydrogels for topical application and sustained drug release: the effect of polyvinylpyrrolidone on the physicomechanical properties of hydrogel. Pharmaceutics. 2023;15(9):2360. doi: 10.3390/pharmaceutics15092360, PMID 37765328.
70. Pınar Yagcılar A, Guven GK, Sefik Caglar E, Okur NU, Siafaka PI. Development and ex vivo / in vitro evaluation of sodium alginate/ hydroxypropyl methylcellulose films for dermal and/or transdermal delivery of p-hydroxycinnamic acid. J Holist Integr Pharm. 2025;6(2):175-83. doi: 10.1016/j.jhip.2025.06.002.
71. Everaert A, Wouters Y, Melsbach E, Zakaria N, Ludwig A, Kiekens F. Optimisation of HPMC ophthalmic inserts with sustained release properties as a carrier for thermolabile therapeutics. Int J Pharm. 2017;528(1-2):395-405. doi: 10.1016/j.ijpharm.2017.06.047, PMID 28624658.
72. Patil AV, Mahajan HS. Modified pea starch-based ocular films of azelastine hydrochloride: development and characterization. Carbohydr Polym Technol Appl. 2021;2:100078. doi: 10.1016/j.carpta.2021.100078.
73. Patel DP, Setty CM, Mistry GN, Patel SL, Patel TJ, Mistry PC. Development and evaluation of ethyl cellulose-based transdermal films of furosemide for improved in vitro skin permeation. AAPS PharmSciTech. 2009;10(2):437-42. doi: 10.1208/s12249-009-9224-3, PMID 19381831.
74. Perioli L, Ambrogi V, Angelici F, Ricci M, Giovagnoli S, Capuccella M. Development of mucoadhesive patches for buccal administration of ibuprofen. J Control Release. 2004;99(1):73-82. doi: 10.1016/j.jconrel.2004.06.005, PMID 15342182.
75. Sulaiman HT, Jabir SA, Kadhem Al-Kinani K. Investigating the effect of different grades and concentrations of PH-sensitive polymer on preparation and characterization of lidocaine hydrochloride as in situ gel buccal spray. Asian J Pharm Clin Res. 2018;11(11):401. doi: 10.22159/ajpcr.2018.v11i11.28492.
76. Taghe S, Mirzaeei S, Ahmadi A. Preparation and evaluation of nanofibrous and film-structured ciprofloxacin hydrochloride inserts for sustained ocular delivery: pharmacokinetic study in rabbit’s eye. Life (Basel). 2023;13(4):913. doi: 10.3390/life13040913, PMID 37109442.
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