Glaucoma, a class of visual neuropathies, is caused by the progressive degeneration of retinal ganglion cells, resulting in vision loss. Acetazolamide, a carbonic anhydrase inhibitor, is typically used to treat glaucoma. To minimize its harmful effects, the current study aimed to develop an acetazolamide-loaded in situ gel by combining natural polymers, such as sodium alginate and xanthan gum (XG), and cold-processable synthetic polymer Aristoflex (AF).
Methods:
Design Expert software was used to identify the optimized formulation by analyzing in vitro drug release study and viscosity data. The selected in situ gel was evaluated based on its physicochemical properties and other nonclinical evaluations.
Results:
Optimized formulation yielded satisfactory results in physicochemical characterizations. The drug-excipient compatibility analysis revealed no drug–polymer interactions. In vitro and ex vivo release studies showed release of up to 70% and 65%, respectively, in 6 h. The intraocular pressure of the rabbit decreased over a long period after applying the optimized gel compared with the marketed formulation.
Conclusion:
Therefore, the research provided a brief explanation that the combination of AF and XG can be utilized in in situ gels owing to its high retention time and reduced harmful effects for ocular illnesses.
HeijlA, LeskeMC, BengtssonB, Early Manifest Glaucoma Trial Group. et al.; Reduction of intraocular pressure and glaucoma progression: Results from the Early Manifest Glaucoma Trial. Arch Ophthalmol2002;120(10):1268–1279; doi: 10.1001/archopht.120.10.1268
2.
HarasymowyczP, BirtC, GooiP, et al.Medical management of glaucoma in the 21st century from a Canadian perspective. J Ophthalmol.2016;2016(1):6509809; doi: 10.1155/2016/6509809
3.
GetasewB. Factors affecting intraocular pressure control in glaucoma patients at Felege Hiwot Referral Hospital, Bahir Dar, Ethiopia. Sci Afr2022;16:e01160; doi: 10.1016/j.sciaf.2022.e01160
4.
BurgoyneCF, DownsJC, BellezzaAJ, et al.The optic nerve head as a biomechanical structure: A new paradigm for understanding the role of IOP-related stress and strain in the pathophysiology of glaucomatous optic nerve head damage. Prog Retin Eye Res2005;24(1):39–73; doi: 10.1016/j.preteyeres.2004.06.001
5.
LiuP, WangF, SongY, et al.Current situation and progress of drugs for reducing intraocular pressure. Ther Adv Chronic Dis2022;13:20406223221140392; doi: 10.1177/20406223221140392
6.
KaurIP, SinghM, KanwarM. Formulation and evaluation of ophthalmic preparations of acetazolamide. Int J Pharm.2000;199(2):119–127; doi: 10.1016/s0378-5173(00)00359-8
7.
HeC, KimSW, LeeDS. In situ gelling stimuli-sensitive block copolymer hydrogels for drug delivery. J Control Release.2008;127(3):189–207; doi: 10.1016/j.jconrel.2008.01.005
8.
GuptaH, JainS, MathurR, et al.Sustained ocular drug delivery from a temperature and pH triggered novel in situ gel system. Drug Deliv.2007;14(8):507–515; doi: 10.1080/10717540701606426
9.
Wójcik-PastuszkaD, NowakM, KwiecieńI, et al.Synthetic polymer-based gels: Release kinetics and biocompatibility assessment. Biomedicines2024;13(1):39; doi: 10.3390/biomedicines13010039
10.
PaulS, DuttaD, SinghR, et al.Revolutionizing ocular drug delivery: Recent advancements in in-situ gel technology. Bull Natl Res Cent2023;47(1):45; doi: 10.1186/s42269-023-01123-9
11.
OaR, KovalevskaIV, MasliiYS, et al.The study of the physicochemical properties of rectal cream samples with carrot extract and rutin. News Pharm2024;107(1):28–33; doi: 10.24959/nphj.24.15
12.
PatelA, CholkarK, AgrahariV, et al.Considerations for polymers used in ocular drug delivery. Front Med (Lausanne)2021;8:787644; doi: 10.3389/fmed.2021.787644
13.
MaanJ, SharmaD, VermaS, et al.Biodegradable polymer-based drug-delivery systems for ocular diseases. Int J Mol Sci2023;24(16):12976; doi: 10.3390/ijms241612976
14.
PatelN, ThakkarV, MetaliaV, et al.Formulation and development of ophthalmic in situ gel for the treatment of ocular inflammation and infection using application of quality by design concept. Drug Dev Ind Pharm2016;42(9):1406–1423; doi: 10.3109/03639045.2015.1137306
15.
NairAB, ShahJ, JacobS, et al.Experimental design, formulation and in vivo evaluation of a novel topical in situ gel system to treat ocular infections. PLoS One2021;16(3):e0248857; doi: 10.1371/journal.pone.0248857
16.
GadadAP, WadklarPD, DandghiP, et al.Thermosensitive in situ gel for ocular delivery of lomefloxacin. Ind J Pharm Edu Res2015;50(2s):S96–S105; doi: 10.5530/ijper.50.2.24
17.
VijayaC, GoudKS. Ion-activated in situ gelling ophthalmic delivery systems of azithromycin. Indian J Pharm Sci2011;73(6):615–620; doi: 10.4103/0250-474x.100234
18.
GuptaH, VelpandianT, JainS. Ion- and pH-activated novel in situ gel system for sustained ocular drug delivery. J Drug Target.2010;18(7):499–505.
19.
MandalS, ThimmasettyMK, PrabhushankarGL, et al.Formulation and evaluation of an in situ gel-forming ophthalmic formulation of moxifloxacin hydrochloride. Int J Pharm Investig2012;2(2):78–82; doi: 10.4103/2230-973x.100042
20.
MittalN, KaurG. In situ gelling ophthalmic drug delivery system: Formulation and evaluation. J of Applied Polymer Sci2014;131(2); doi: 10.1002/app.39788
21.
DestruelPL, ZengN, MauryM, et al.In vitro and in vivo evaluation of in situ gelling systems for sustained topical ophthalmic delivery: State of the art and beyond. Drug Discov Today2017;22(4):638–651; doi: 10.1016/j.drudis.2016.12.008
22.
ZhangYX, WangLY, DaiJK, et al.The comparative study of cocrystal/salt in simultaneously improving solubility and permeability of acetazolamide. J Mol Struct2019;1184:225–232; doi: 10.1016/j.molstruc.2019.01.090
23.
RahimzadehG, SaeediM, NokhodchiA, et al.Evaluation of in situ gel-forming eye drop containing bacteriophage against Pseudomonas aeruginosa keratoconjunctivitis in vivo. Bioimpacts2021;11(4):281–287; doi: 10.34172/bi.2021.10
24.
Vila-FarresX, SauveK, OhJ, et al.Rapid bacteriolysis of Staphylococcus aureus by lysin exebacase. Microbiol Spectr2023;11(5):e01906–23; doi: 10.1128/spectrum.01906-23
25.
RanchKM, MaulviFA, NaikMJ, et al.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 Pharm2019;554:264–275; doi: 10.1016/j.ijpharm.2018.11.016
26.
WaltersTR, DuBinerHB, CarpenterSP, Bimatoprost Circadian IOP Study Group. et al.; 24-hour IOP control with once-daily bimatoprost, timolol gel-forming solution, or latanoprost: A 1-month, randomized, comparative clinical trial. Surv Ophthalmol.2004;49(Suppl 1):S26–S35; doi: 10.1016/j.survophthal.2003.12.017
27.
RojekB, WesolowskiM. FTIR and TG analyses coupled with factor analysis in a compatibility study of acetazolamide with excipients. Spectrochim Acta A Mol Biomol Spectrosc2019;208:285–293; doi: 10.1016/j.saa.2018.10.020
28.
PathakMK, ChhabraG, PathakK. Design and development of a novel pH-triggered nanoemulsified in situ ophthalmic gel of fluconazole: Transcorneal permeation, corneal toxicity and irritation testing. Drug Dev Ind Pharm.2013;39(5):780–790; doi: 10.3109/03639045.2012.707203
29.
MoraisM, CoimbraP, PinaME. Comparative analysis of morphological and release profiles in ocular implants of acetazolamide prepared by electrospinning. Pharmaceutics.2021;13(2):260; doi: 10.3390/pharmaceutics13020260
30.
SahooRN, DashR, NandiS, et al.Controlled crystallization of acetazolamide from aqueous polymeric solutions for enhancing dissolution rate: Application of statistical moment theory and molecular docking. J Sci Ind Res2023;82(5); doi: 10.56042/jsir.v82i05.1080
31.
ChaudhariLP, PatelSN. Corrosion inhibition study of expired acetazolamide on mild steel in dilute hydrochloric acid solution. J Bio Tribo Corros2019;5(1):1–3; doi: 10.1007/s40735-018-0212-6
