Development and Evaluation of in situ eye gel for delivery of gatifloxacin and betamethasone sodium phosphate
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Abstract
Drug delivery to ocular tissues is challenging due to the rapid removal of instilled drugs due to the low resident time in ocular tissues. The study aimed to formulate an ophthalmic in situ gel that delivers two drugs (betamethasone sodium phosphate [BSP] and gatifloxacin [GTN]). The new combination will allow the simultaneous administration and extended release of the two drugs, which could potentially improve resident time in ocular tissues, patient compliance, and treatment adherence.
Formulations containing different gelling agents at different concentrations were prepared to choose the optimum combination regarding physical properties and release. Formulations containing 17% poloxamer 407 and 0.5% gellan gum with different percentages of methylcellulose were prepared and compared regarding gelation temperature, gelling capacity, gelation time, and release and mucoadhesive, permeation study. Increasing the concentration of MC enhanced all the physical properties of the poloxamer-gellan gum gel.
The optimum formula (F3) which contains 0.3% MC had a gelation time of 5 sec. at 31oC and remained in gel form for 24 hr. Both drugs had extended-release time and increased the viscosity and mucoadhesion force of the preparation. The results indicated an outsized increase in viscosity at 37°C with the addition of MC which provided sustained release of the drug over 10 hours. and the formulation is isotonic to the eye as well no irritation on the rabbit eye was observed when tested on animals.
Conclusion: F3 in situ gel was used to produce a simultaneous and prolonged release of the two drugs. The capacity to administer hydrophilic and hydrophobic medications using a single formulation, eliminating the need for two drops, will increase patient compliance and, consequently, treatment compliance.
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1- Alsaidan, O.A., et al., Development of Ciprofloxacin-Loaded Bilosomes In-Situ Gel for Ocular Delivery: Optimization, In-Vitro Characterization, Ex-Vivo Permeation, and Antimicrobial Study. 2022. 8(11): p. 687. DOI: https://doi.org/10.3390/gels8110687
2- Ranch, K., et al., Development of in situ Ophthalmic gel of Dexamethasone Sodium Phosphate and Chloramphenicol: A Viable Alternative to Conventional Eye Drops. Journal of Applied Pharmaceutical Science, 2017. 7: p. 101-108.
3- Abul Kalam, M., et al., Gelrite-Based In Vitro Gelation Ophthalmic Drug Delivery System of Gatifloxacin. Journal of Dispersion Science and Technology, 2008. 29: p. 89-96.
4- Kurniawansyah, I., et al., A REVIEW ON POLOXAMER AND HYDROXY PROPYL METHYL CELLULOSE COMBINATION AS THERMORESPONSIVE POLYMERS IN NOVEL OPHTHALMIC IN SITU GEL FORMULATION AND THEIR CHARACTERIZATION. International Journal of Applied Pharmaceutics, 2021.
5- Gb, P. and E. Narendra, Formulation and evaluation of in situ mucoadhesive ophthalmic hydrogel for sustained delivery of pefloxacin mesylate. International Journal of Pharmacy and Pharmaceutical Sciences, 2015. 7: p. 345-350.
6- Kumar, L., et al., Insitu gel: A novel system for ocular drug delivery. International Journal of Pharmaceutical Sciences Review and Research, 2011. 9: p. 83-91.
7- Wu, Y., et al., Research progress of in-situ gelling ophthalmic drug delivery system. Asian J Pharm Sci, 2019. 14(1): p. 1-15. DOI: https://doi.org/10.1016/j.ajps.2018.04.008
8- Tagalpallewar, A., et al., Formulation, Optimization and Evaluation of Ion Triggered Ophthalmic in Situ Gel. Journal of Pharmaceutical Research International, 2021: p. 58-77. DOI: https://doi.org/10.9734/jpri/2021/v33i28A31511
9- Kadam, A., et al., DESIGN AND EVALUATION OF MODIFIED CHITOSAN BASED IN SITU GEL FOR OCULAR DRUG DELIVERY. International Journal of Pharmacy and Pharmaceutical Sciences, 2017. 9: p. 87. DOI: https://doi.org/10.22159/ijpps.2017v9i11.20938
10- Morsi, N., et al., Ketoroloac tromethamine loaded nanodispersion incorporated into thermosensitive in situ gel for prolonged ocular delivery. Int J Pharm, 2016. 506(1-2): p. 57-67. DOI: https://doi.org/10.1016/j.ijpharm.2016.04.021
11- Szalai, B., et al., Design and Optimization of In Situ Gelling Mucoadhesive Eye Drops Containing Dexamethasone. Gels, 2022. 8(9). DOI: https://doi.org/10.3390/gels8090561
12- Pandey, M., et al., Potential of Stimuli-Responsive In Situ Gel System for Sustained Ocular Drug Delivery: Recent Progress and Contemporary Research. Polymers (Basel), 2021. 13(8). DOI: https://doi.org/10.3390/polym13081340
13- Kurniawansyah, I.S., et al., Comparative Study of In Situ Gel Formulation Based on the Physico-Chemical Aspect: Systematic Review. 2023. 9(8): p. 645. DOI: https://doi.org/10.3390/gels9080645
14- Rawat, M. and G.J.J.o.P.N.R. Gnanarajan, Development And In-Vitro Characterization Of Liposomal Embedded In-Situ Ocular Gel Of Dorzolamide Hydrochloride For The Treatment Of Glaucoma. 2023: p. 25-36.
15- Sultana, Y., et al., Evaluation of carbopol-methyl cellulose based sustained-release ocular delivery system for pefloxacin mesylate using rabbit eye model. Pharm Dev Technol, 2006. 11(3): p. 313-9. DOI: https://doi.org/10.1080/10837450600767698
16- Hezhen, T., et al., Effect of gatifloxacin in the treatment of ophthalmological diseases and continuous nursing intervention. Pak J Pharm Sci, 2018. 31(4(Special)): p. 1707-1712.
17- Sabry, H.S., A.D.H. Al-Shohani, and S.Z. Mahmood, Formulation and Evaluation of Levofloxacin and Betamethasone Ophthalmic Emulgel. J Pharm Bioallied Sci, 2021. 13(2): p. 205-211. DOI: https://doi.org/10.4103/jpbs.JPBS_338_20
18- Chan, C.Y., et al., Otologic safety of intratympanic N-acetylcysteine in an animal model. International Journal of Pediatric Otorhinolaryngology, 2023. 173: p. 111702. DOI: https://doi.org/10.1016/j.ijporl.2023.111702
19- Scoper, S.V., et al., Ocular distribution, bactericidal activity and settling characteristics of TobraDex® ST ophthalmic suspension compared with TobraDex® ophthalmic suspension. Advances in Therapy, 2008. 25(2): p. 77-88. DOI: https://doi.org/10.1007/s12325-008-0019-9
20- Eaga, C., J. Kandukuri, and V. Allenki, Preparation and Evaluation of In-Situ-Gels for Ocular Drug Delivery. Journal of Pharmacy Research, 2009. 2.
21- Huang, Y., et al., The gelling behavior of gellan in the presence of different sodium salts. International Journal of Biological Macromolecules, 2021. 193: p. 768-777. DOI: https://doi.org/10.1016/j.ijbiomac.2021.10.173
22- Khule, M. and S. Vyavahare, A Review: in-situ Gel Drug Delivery System. 2021. 9: p. 2455-6211.
23- Sun, J. and Z. Zhou, A novel ocular delivery of brinzolamide based on gellan gum: in vitro and in vivo evaluation. Drug Des Devel Ther, 2018. 12: p. 383-389. DOI: https://doi.org/10.2147/DDDT.S153405
24- Albazzaz, F. and M. Alkotaji, Ophthalmic in-situ sustained gel of ciprofloxacin, preparation and evaluation study. International Journal of Applied Pharmaceutics, 2018. 10: p. 153. DOI: https://doi.org/10.22159/ijap.2018v10i4.26885
25- Dewan, M., et al., Effect of gellan gum on the thermogelation property and drug release profile of Poloxamer 407 based ophthalmic formulation. International Journal of Biological Macromolecules, 2017. 102: p. 258-265. DOI: https://doi.org/10.1016/j.ijbiomac.2017.03.194
26- Salmo, H.M., et al., Development and In-Vitro Clinical Study of Tinidazole-Chlorhexidine Gluconate ophthalmic suspension for Treatment of Keratitis. 2007. 4(1): p. 55-63. DOI: https://doi.org/10.32947/ajps.v4i1.380
27- Liu, Z., et al., Study of an alginate/HPMC-based in situ gelling ophthalmic delivery system for gatifloxacin. International Journal of Pharmaceutics, 2006. 315(1): p. 12-17. DOI: https://doi.org/10.1016/j.ijpharm.2006.01.029
28- Mandal, S., et al., Formulation and evaluation of an in situ gel-forming ophthalmic formulation of moxifloxacin hydrochloride. Int J Pharm Investig, 2012. 2(2): p. 78-82. DOI: https://doi.org/10.4103/2230-973X.100042
29- Ali, M.H.M. and W.K.J.A.M.J.o.P.S. Ali, Preparation and Evaluation of Emulgel as Topical Drug Delivery for Nimesulide by Using Conventional Emulsion. 2019. 19(4): p. 16-26. DOI: https://doi.org/10.32947/ajps.v19i4.629
30- Amer, Z., Z. Mahdi, and A. Alhamdany, Formulation and Evaluation of Ocular in-Situ gelling system containing Ciprofloxacin and Naproxen Sodium. Research Journal of Pharmacy and Technology, 2021. 14: p. 91-95. DOI: https://doi.org/10.5958/0974-360X.2021.00017.2
31- Khatera, N.A.A., et al., In-situ gelling ophthalmic formulations for sustained release and enhanced ocular delivery of fluconazole. 2016. 11(2): p. 43-51.
32- Alhaddad, M., Fabrication and characterization of new combination ocular insert for the combined delivery of tinidazole and levofloxacin. 2023.
33- Alkufi, H.k. and H.J. Kassab. Formulation and Evaluation of Sustained Release Sumatriptan Mucoadhesive Intranasal in-Situ Gel. 2019.
34- Wafa, H.G., et al., Ocular films versus film-forming liquid systems for enhanced ocular drug delivery. Drug Deliv Transl Res, 2021. 11(3): p. 1084-1095. DOI: https://doi.org/10.1007/s13346-020-00825-1
35- 35. Gadad, A.P., et al., Thermosensitive in situ gel for ocular delivery of lomefloxacin. Indian Journal of Pharmaceutical Education and Research, 2016. 50: p. S96-S105.
36- Rathore, K.S., Development and in vivo in vitro characterizations of timolol maleate in-situ gels. International Journal of Pharma and Bio Sciences, 2011. 2: p. 248-263.
37- Pawar, P., et al., Hp-β-CD-voriconazole in situ gelling system for ocular drug delivery: in vitro, stability, and antifungal activities assessment. Biomed Res Int, 2013. 2013: p. 341218. DOI: https://doi.org/10.1155/2013/341218
38- Abbas, M.N., et al., Nanoparticles Loaded Thermoresponsive In Situ Gel for Ocular Antibiotic Delivery against Bacterial Keratitis. 2022. 14(6): p. 1135. DOI: https://doi.org/10.3390/polym14061135
39- Kalam, M.A., et al., Gelrite‐Based In Vitro Gelation Ophthalmic Drug Delivery System of Gatifloxacin. 2008. 29: p. 89 - 96. DOI: https://doi.org/10.1080/01932690701688482
40- Soliman, K.A., et al., Poloxamer-based in situ gelling thermoresponsive systems for ocular drug delivery applications. Drug Discovery Today, 2019. 24(8): p. 1575-1586. DOI: https://doi.org/10.1016/j.drudis.2019.05.036
41- Deepthi, S. and J. Jose, Novel hydrogel-based ocular drug delivery system for the treatment of conjunctivitis. Int Ophthalmol, 2019. 39(6): p. 1355-1366. DOI: https://doi.org/10.1007/s10792-018-0955-6
42- Budumuru, P., R. Nagaraju, and D. Prasanth, A comprehensive review on in situ gels. International Journal of Applied Pharmaceutics, 2020. 12: p. 24-33. DOI: https://doi.org/10.22159/ijap.2020v12i6.38918
43- Youssef, A., N. Dudhipala, and S. Majumdar, Ciprofloxacin Loaded Nanostructured Lipid Carriers Incorporated into In-Situ Gels to Improve Management of Bacterial Endophthalmitis. 2020. 12(6): p. 572. DOI: https://doi.org/10.3390/pharmaceutics12060572
44- Abraham, S., et al., Sustained ophthalmic delivery of ofloxacin from an ion-activated in situ gelling system. Pak J Pharm Sci, 2009. 22(2): p. 175-9.
45- Tassew, N.G., et al., Tolerability Assessment of Formulation pH in New Zealand White Rabbits Following Intravitreal Administration. Toxicol Pathol, 2021. 49(3): p. 605-609. DOI: https://doi.org/10.1177/0192623320969667
46- Dewan, M., et al., Effect of methyl cellulose on gelation behavior and drug release from poloxamer based ophthalmic formulations. Int J Biol Macromol, 2015. 72: p. 706-10. DOI: https://doi.org/10.1016/j.ijbiomac.2014.09.021
47- Bain, M.K., et al., Effect of PVA on the gel temperature of MC and release kinetics of KT from MC based ophthalmic formulations. International Journal of Biological Macromolecules, 2012. 50(3): p. 565-572. DOI: https://doi.org/10.1016/j.ijbiomac.2012.01.025
48- El-Kamel, A.H., In vitro and in vivo evaluation of Pluronic F127-based ocular delivery system for timolol maleate. International Journal of Pharmaceutics, 2002. 241(1): p. 47-55. DOI: https://doi.org/10.1016/S0378-5173(02)00234-X
49- Gupta, B., et al., Cellulosic Polymers for Enhancing Drug Bioavailability in Ocular Drug Delivery Systems. Pharmaceuticals (Basel), 2021. 14(11). DOI: https://doi.org/10.3390/ph14111201
50- Vodithala, S., et al., Development and evaluation of thermoreversible ocular gels of ketorolac tromethamine. Int J Biopharm, 2010. 1: p. 39-45.
51- KURNIAWANSYAH, I.S., et al., A review on poloxamer and hydroxy propyl methyl cellulose combination as thermoresponsive polymers in novel ophthalmic in situ gel formulation and their characterization. 2021. 13: p. 27-31. DOI: https://doi.org/10.22159/ijap.2021v13i1.39697
52- Arthanari, S., et al., Preparation and characterization of gatifloxacin-loaded alginate/poly (vinyl alcohol) electrospun nanofibers. Artif Cells Nanomed Biotechnol, 2016. 44(3): p. 847-52.
53- Zhang, Y., et al., Preparation and characterization of (betamethasone sodium phosphate intercalated layered double hydroxide)@liposome nanocomposites. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2017. 529: p. 824-831. DOI: https://doi.org/10.1016/j.colsurfa.2017.06.063