Abstract
Background: Ocular in situ gels (ISG) are an adequate substitute to overcome the pitfalls of conventional eye drops as they acquaintance the advantages of solutions, including accuracy, dosing frequency, and ease of administration with prolonged contact with the ocular membrane.
Objective: The present investigation aims to develop the ion-triggered in situ gel (ITISG) system for the convenient administration of Ciprofloxacin HCl (CFH) and Olopatadine HCl (OLH) in combination by employing gellan gum to prolong the pre-corneal residence, optic bioavailability and declines dosing frequency.
Methods: The ISG material and critical quality attributes (CQA) were identified. Quality by Design (QbD) was established to optimize the formulation. Nine experimental formulations were designed (F1-F9) and assigned to distinct physicochemical and in vitro examinations.
Results: Optimized batch F2 exhibited all the findings within acceptable limits. The Ion-triggered ISG technique exhibits maximum drug release over a 240-min cycle, much more significant than conventional eyedrops (60 min), suggesting sustained drug distribution and superior corneal penetration and absorption.
Conclusion: Comprehensive findings of the present investigation conclude that the CFH and OLH would be effectively formulated as an ion-triggered ISG system to manage several drawbacks associated with prolonged release, ocular retention, and better corneal penetration compared with conventional eyedrops.
Graphical Abstract
[http://dx.doi.org/10.1016/j.jconrel.2007.07.009] [PMID: 17719120]
[http://dx.doi.org/10.1016/j.ijpharm.2006.01.029] [PMID: 16616442]
[http://dx.doi.org/10.1177/1120672118769776] [PMID: 29756507]
[http://dx.doi.org/10.3390/pr9111949]
[http://dx.doi.org/10.1002/aic.690491202]
[http://dx.doi.org/10.1016/j.ijbiomac.2020.02.097] [PMID: 32057864]
[http://dx.doi.org/10.1016/j.addr.2017.12.017] [PMID: 29288733]
[http://dx.doi.org/10.1155/2012/187824]
[http://dx.doi.org/10.1080/1744666X.2023.2200165] [PMID: 37038974]
[http://dx.doi.org/10.3390/pharmaceutics10010010] [PMID: 29342879]
[http://dx.doi.org/10.3390/pharmaceutics12090859] [PMID: 32927595]
[http://dx.doi.org/10.1016/j.ajps.2018.04.008] [PMID: 32104434]
[http://dx.doi.org/10.1016/j.jconrel.2020.01.057] [PMID: 32027938]
[http://dx.doi.org/10.22270/jddt.v9i1.2231]
[http://dx.doi.org/10.15406/japlr.2016.02.00022]
[http://dx.doi.org/10.1016/j.rinphs.2015.06.001] [PMID: 26949596]
[http://dx.doi.org/10.1080/713840402] [PMID: 12944139]
[http://dx.doi.org/10.3390/pharmaceutics12060572] [PMID: 32575524]
[http://dx.doi.org/10.1016/j.ijpharm.2018.11.016] [PMID: 30423418]
[http://dx.doi.org/10.3390/pharmaceutics15010108] [PMID: 36678736]
[http://dx.doi.org/10.1007/978-1-4614-4439-8_7]
[http://dx.doi.org/10.1037/a0015826] [PMID: 19719358]
[http://dx.doi.org/10.3109/03639045.2015.1137306] [PMID: 26716613]
[http://dx.doi.org/10.1021/nn405674m] [PMID: 24274814]
[http://dx.doi.org/10.1016/j.bfopcu.2017.09.006]
[http://dx.doi.org/10.1016/j.bmcl.2015.02.013] [PMID: 25740159]
[http://dx.doi.org/10.22161/ijaers.5.6.28]
[http://dx.doi.org/10.4103/0975-1483.90233] [PMID: 22224031]
[http://dx.doi.org/10.1186/s43094-020-00140-z]
[http://dx.doi.org/10.1016/j.ajps.2016.07.006] [PMID: 32104308]
[http://dx.doi.org/10.3390/pharmaceutics12030287] [PMID: 32210126]
[http://dx.doi.org/10.4103/2230-973X.100042] [PMID: 23119236]
[http://dx.doi.org/10.1155/2014/861904] [PMID: 24772038]
[http://dx.doi.org/10.1016/j.ejps.2021.105906] [PMID: 34118409]
[http://dx.doi.org/10.3390/ph16060864] [PMID: 37375811]
[http://dx.doi.org/10.3109/10717544.2014.987333] [PMID: 25579467]
[http://dx.doi.org/10.1021/ja065867x] [PMID: 17117838]
[http://dx.doi.org/10.1016/j.ijpharm.2022.121512] [PMID: 35085730]
[http://dx.doi.org/10.3390/gels8120802] [PMID: 36547326]
[http://dx.doi.org/10.1016/j.xphs.2018.08.013] [PMID: 30170009]
[http://dx.doi.org/10.4103/kleuhsj.kleuhsj_131_17]
[http://dx.doi.org/10.1016/j.jpba.2008.03.012] [PMID: 18514459]
[PMID: 23675017]
[http://dx.doi.org/10.3390/pharmaceutics14112324] [PMID: 36365143]
[http://dx.doi.org/10.2217/nnm.09.75] [PMID: 19958220]
[http://dx.doi.org/10.1016/j.biopha.2016.06.024] [PMID: 27470557]
[http://dx.doi.org/10.3390/ma12081202] [PMID: 31013801]
[http://dx.doi.org/10.1631/jzus.B0920229] [PMID: 19946951]
[http://dx.doi.org/10.1136/bjophthalmol-2019-315623]
[http://dx.doi.org/10.1016/S2221-1691(12)60216-0] [PMID: 23570001]
[http://dx.doi.org/10.1016/j.envint.2015.09.013] [PMID: 26411644]
[http://dx.doi.org/10.1371/journal.pone.0172306]
[http://dx.doi.org/10.1155/2019/5372530] [PMID: 31178944]
[http://dx.doi.org/10.1128/JCM.02351-15]
[http://dx.doi.org/10.1128/spectrum.03161-22]
[http://dx.doi.org/10.4103/2230-973X.143131] [PMID: 25426444]
[http://dx.doi.org/10.3390/pharmaceutics14101995] [PMID: 36297431]
[http://dx.doi.org/10.1088/1757-899X/736/2/022030]
[PMID: 24511475]
[http://dx.doi.org/10.4103/0975-9476.85550] [PMID: 22022154]
[http://dx.doi.org/10.1016/j.ijpharm.2015.05.023] [PMID: 25980731]
[http://dx.doi.org/10.1093/ps/79.6.827] [PMID: 10875763]
[http://dx.doi.org/10.1177/1091581816672187] [PMID: 27733445]
[http://dx.doi.org/10.1016/j.tiv.2021.105255] [PMID: 34743969]
[http://dx.doi.org/10.1016/j.jconrel.2018.03.003] [PMID: 29518465]
[http://dx.doi.org/10.1016/j.jddst.2016.03.011]
[http://dx.doi.org/10.1155/2015/432376] [PMID: 25654129]