A COMPREHENSIVE CHEMICAL CHARACTERIZATION OF IN SITU OPHTHALMIC GEL

Authors

  • INSAN SUNAN KURNIAWANSYAH Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, West Java, Indonesia
  • IYAN SOPYAN PUSDI Drug Delivery and Drug Disposition Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, West Java, Indonesia
  • TAOFIK RUSDIANA Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, West Java, Indonesia
  • FIRDA SILVIA PRAMASHELA Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, West Java, Indonesia
  • ANAS SUBARNAS Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, West Java, Indonesia

DOI:

https://doi.org/10.22159/ijap.2021v13i6.42457

Keywords:

Chemical characteristics, In situ gel, Ophthalmic, Irritation

Abstract

In situ ophthalmic gel is a gel preparation that is initially in the form of ophthalmic solution that dripped into the eye and then the solution turns into a gel after contact with the surface of the eye. In situ gel will undergo phase change to gel due to pH, electrolyte and temperature conditions. So that the preparation of ophthalmic in situ gel is required characterization to make sure that the prepared preparations meet the standards and are safe when used. Chemical evaluation includes pH, concentration, chemical bonds, crystallization and drug and polymer interactions. The purpose of this review is to discuss the evaluation methods used in preparations, and to see whether the pH of in situ ophthalmic gel formulation that provided can met the ideal pH requirements of the eye, so that the ophthalmic in situ gel preparation would not causing irritation and liquid tear production.

Downloads

Download data is not yet available.

References

Nanjawade BK, Manvi FV, Manjappa AS. In situ-forming hydrogels for sustained ophthalmic drug delivery. J Controlled Release. 2007;122(2):119-34. doi: 10.1016/j.jconrel. 2007.07.009, PMID 17719120.

Ludwig A. The use of mucoadhesive polymers in ocular drug delivery. Adv Drug Delivery Rev. 2005;57(11):1595-639. doi: 10.1016/j.addr.2005.07.005, PMID 16198021.

Cholkar K, Patel SP, Vadlapudi AD, Mitra AK. Novel strategies for anterior segment ocular drug delivery. J Ocul Pharmacol Ther. 2013;29(2):106-23. doi: 10.1089/jop.2012.0200, PMID 23215539.

Kumar K, Dhawan N, Sharma H, Vaidya S, Vaidya B. Bioadhesive polymers: novel tool for drug delivery. Artif Cells Nanomed Biotechnol. 2014;42(4):274-83. doi: 10.3109/21691401.2013.815194, PMID 23859698.

Sathali AH, Mohanambal E, Arun K. Formulation and evaluation of pH triggered in situ gelling system of levofloxacin. Indian J Pharm Educ Res. 2011;45:58-64.

Nagalakshmi S, Seshank RR, Shanmuganathan S. Formulation and evaluation of stimuli sensitive pH triggered in-situ gelling system of fluconazole in ocular drug delivery. Int J Pharm Sci Res. 2014;5:1339-44.

Nanjawade BK, Manjappa AS, Murthy RS, Pol YD. A novel pH triggered in situ gel for sustained ophthalmic delivery of ketorolac. Asian J Pharm Sci. 2009;4:189-99.

Matanovic MR, Kristl J, Grabnar PA. Thermoresponsive polymers: insights into decisive hydrogel characteristics, mechanisms of gelation, and promising biomedical applications. Int J Pharm. 2014;472(1-2):262-75. doi: 10.1016/j.ijpharm.2014.06.029, PMID 24950367.

Singh NK, Lee DS. In situ gelling pH- and temperature-sensitive biodegradable block copolymer hydrogels for drug delivery. J Controlled Release. 2014;193:214-27. doi: 10.1016/ j.jconrel.2014.04.056, PMID 24815421.

Patel A, Cholkar K, Agrahari V, Mitra AK. Ocular drug delivery systems: an overview. World J Pharmacol. 2013;2(2):47-64. doi: 10.5497/wjp.v2.i2.47, PMID 25590022.

Lajri G, Ravindranath S. Ophthalmic pH sensitive in-situ gel: a review. J Drug Delivery Ther. 2019;9:682-9.

Mandal S, Thimmasetty MK, Prabhushankar G, Geetha M. Formulation and evaluation of an in situ gel-forming ophthalmic formulation of moxifloxacin hydrochloride. Int J Pharm Investig. 2012;2(2):78-82. doi: 10.4103/2230-973X.100042, PMID 23119236.

MA Fathalla Z, Vangala A, Longman M, Khaled KA, Hussein AK, El-Garhy OH, Alany RG. Poloxamer-based thermoresponsive ketorolac tromethamine in situ gel preparations: design, characterisation, toxicity and transcorneal permeation studies. Eur J Pharm Biopharm. 2017;114:119-34. doi: 10.1016/j.ejpb.2017.01.008, PMID 28126392.

Davaran S, Lotfipour F, Sedghipour N, Sedghipour MR, Alimohammadi S, Salehi R. Preparation and in vivo evaluation of in situ gel system as dual thermo-/pH-responsive nanocarriers for sustained ocular drug delivery. J Microencapsul. 2015;32(5):511-9. doi: 10.3109/ 02652048.2015.1065915, PMID 26190215.

Allam A, El-Mokhtar MA, Elsabahy M. Vancomycin-loaded niosomes integrated within pH-sensitive in-situ forming gel for treatment of ocular infections while minimizing drug irritation. J Pharm Pharmacol. 2019;71(8):1209-21. doi: 10.1111/jphp.13106, PMID 31124593.

Bhalerao H, Koteshwara KB, Chandran S. Levofloxacin hemihydrate in situ Gelling ophthalmic Solution: formulation Optimization and in vitro and in vivo Evaluation. AAPS PharmSciTech. 2019;20(7):272. doi: 10.1208/s12249-019-1489-6, PMID 31372767.

Sun J, Zhou Z. A novel ocular delivery of brinzolamide based on gellan gum: in vitro and in vivo evaluation. Drug Des Devel Ther. 2018;12:383-9. doi: 10.2147/DDDT.S153405, PMID 29503531.

Huang W, Zhang N, Hua H, Liu T, Tang Y, Fu L, Yang Y, Ma X, Zhao Y. Preparation, pharmacokinetics and pharmacodynamics of ophthalmic thermosensitive in situ hydrogel of betaxolol hydrochloride. Biomed Pharmacother. 2016;83:107-13. doi: 10.1016/j.biopha.2016.06.024, PMID 27470557.

Ibrahim MM, Abd-Elgawad AH, Soliman OAE, Jablonski MM. Stability and ocular pharmacokinetics of celecoxib-loaded nanoparticles topical ophthalmic formulations. J Pharm Sci. 2016;105(12):3691-701. doi: 10.1016/j.xphs.2016.09.019, PMID 27789031.

Ahmed TA, Aljaeid BM. A potential in situ gel formulation loaded with novel fabricated poly(Lactide-co-glycolide) nanoparticles for enhancing and sustaining the ophthalmic delivery of ketoconazole. Int J Nanomed. 2017;12:1863-75. doi: 10.2147/IJN.S131850, PMID 28331311.

Jaiswal M, Kumar M, Pathak K. Zero order delivery of itraconazole via polymeric micelles incorporated in situ ocular gel for the management of fungal keratitis. Colloids Surf B Biointerfaces. 2015;130:23-30. doi: 10.1016/j.colsurfb.2015.03.059, PMID 25889081.

Kesarla R, Tank T, Vora PA, Shah T, Parmar S, Omri A. Preparation and evaluation of nanoparticles loaded ophthalmic in situ gel. Drug Delivery. 2016;23(7):2363-70. doi: 10.3109/10717544.2014.987333, PMID 25579467.

Li P, Wang S, Chen H, Zhang S, Yu S, Li Y, Cui M, Pan W, Yang X. A novel ion-activated in situ gelling ophthalmic delivery system based on κ-carrageenan for acyclovir. Drug Dev Ind Pharm. 2018;44(5):829-36. doi: 10.1080/03639045.2017.1414232, PMID 29212376.

Tatke A, Dudhipala N, Janga KY, Balguri SP, Avula B, Jablonski MM. In situ gel of triamcinolone acetonide-loaded solid lipid nanoparticles for improved topical ocular delivery: Tear kinetics and ocular disposition studies. Nanomaterials. 2019;9:1-17.

Sapino S, Peira E, Chirio D, Chindamo G, Guglielmo S, Oliaro-Bosso S, Barbero R, Vercelli C, Re G, Brunella V, Riedo C, Fea AM, Gallarate M. Thermosensitive nanocomposite hydrogels for intravitreal delivery of cefuroxime. Nanomaterials (Basel). 2019;9(10). doi: 10.3390/nano9101461, PMID 31618969.

Khan S, Warade S, Singhavi DJ. Improvement in ocular bioavailability and prolonged delivery of tobramycin sulfate following topical ophthalmic administration of drug-loaded mucoadhesive microparticles incorporated in thermosensitive in situ gel. J Ocul Pharmacol Ther. 2018;34(3):287-97. doi: 10.1089/jop.2017.0079, PMID 29211593.

Yang X, Shah SJ, Wang Z, Agrahari V, Pal D, Mitra AK. Nanoparticle-based topical ophthalmic formulation for sustained release of stereoisomeric dipeptide prodrugs of ganciclovir. Drug Delivery. 2016;23(7):2399-409. doi: 10.3109/10717544.2014.996833, PMID 25564964.

Devi S, Saini V, Kumar M, Bhatt S, Gupta S, Deep A. A novel approach of drug localization through development of polymeric micellar system containing azelastine HCl for ocular delivery. Pharm Nanotechnol. 2019;7(4):314-27. doi: 10.2174/2211738507666190726162000, PMID 31362666.

Jain P, Jaiswal CP, Mirza MA, Anwer MK, Iqbal Z. Preparation of levofloxacin loaded in situ gel for sustained ocular delivery: in vitro and ex vivo evaluations. Drug Dev Ind Pharm. 2020;46(1):50-6. doi: 10.1080/03639045.2019.1698598, PMID 31818154.

Shelley H, Rodriguez Galarza RM, Duran SH, Abarca EM, Babu RJ. In situ gel formulation for enhanced ocular delivery of nepafenac. J Pharm Sci. 2018;107(12):3089-97. doi: 10.1016/j.xphs.2018.08.013, PMID 30170009.

Pandurangan DK, Bodagala P, Palanirajan VK, Govindaraj S. Formulation and evaluation of voriconazole ophthalmic solid lipid nanoparticles in situ gel. Int J Pharm Investig. 2016;6(1):56-256-62. doi: 10.4103/2230-973X.176488, PMID 27014620.

Wen Y, Ban J, Mo Z, Zhang Y, An P, Liu L, Xie Q, Du Y, Xie B, Zhan X, Tan L, Chen Y, Lu ZYi feng wen, et al. A potential nanoparticle-loaded in situ gel for enhanced and sustained ophthalmic delivery of dexamethasone. Nanotechnology. 2018;29(42):425101:425101. doi: 10.1088/1361-6528/aad7da.

Barse RK, Tagalpallewar AA, Kokare CR, Sharma JP, Sharma PK. Formulation and ex vivo–in vivo evaluation of pH-triggered brimonidine tartrate in situ gel for the glaucoma treatment using application of 32 factorial design. Drug Dev Ind Pharm. 2018;44(5):800-7. doi: 10.1080/03639045.2017.1414229, PMID 29228819.

Zhu L, Ao J, Li P. A novel in situ gel base of deacetylase gellan gum for sustained ophthalmic drug delivery of ketotifen: in vitro and in vivo evaluation. Drug Des Dev Ther. 2015;9:3943-9. doi: 10.2147/DDDT.S87368, PMID 26251573.

Bhalerao H, Koteshwara KB, Chandran S. Brinzolamide dimethyl sulfoxide in situ gelling ophthalmic solution: formulation optimisation and in vitro and in vivo Evaluation. AAPS PharmSciTech. 2020;21(2):1–1569. doi: 10.1208/s12249-019-1555-0, PMID 31950311.

Yadav M, Guzman-Aranguez A, Perez de Lara MJ, Singh M, Singh J, Kaur IP. Bimatoprost loaded nanovesicular long-acting sub-conjunctival in-situ gelling implant: in vitro and in vivo evaluation. Mater Sci Eng C Mater Biol Appl. 2019;103;109730:109730. doi: 10.1016/j.msec.2019.05.015.

Ameeduzzafar, Imam SS, Bukhari SNA, Ali AAmeeduzzafar, Imam SS, Bukhari SNA, Ali A. Preparation and evaluation of novel chitosan: gelrite ocular system containing besifloxacin for topical treatment of bacterial conjunctivitis: scintigraphy, ocular irritation and retention assessment. Artificial Cells, Nanomed Biotechnol. 2018;46(5):959-67. doi: 10.1080/21691401.2017.1349779.

Kouchak M, Mahmoodzadeh M, Farrahi F. Designing of a pH-triggered carbopol®/HPMC in situ gel for ocular delivery of dorzolamide HCl: in vitro, in vivo, and eex vvivo evaluation. AAPS PharmSciTech. 2019;20(5):1–8210. doi: 10.1208/s12249-019-1431-y, PMID 31161269.

Makwana SB, Patel VA, Parmar SJ. Development and characterization of in-situ gel for ophthalmic formulation containing ciprofloxacin hydrochloride. Results Pharma Sci. 2016;6:1-6. doi: 10.1016/j.rinphs.2015.06.001, PMID 26949596.

Okur NU, Yozgatli V, Okur ME. In vitro–in vivo evaluation of tetrahydrozoline-loaded ocular in situ gels on rabbits for allergic conjunctivitis management. Drug Dev Res. 2020 April;81(6):1–12716-27. doi: 10.1002/ddr.21677, PMID 32359095.

Morsi N, Ibrahim M, Refai H, El Sorogy H. Nanoemulsion-based electrolyte triggered in situ gel for ocular delivery of acetazolamide. Eur J Pharm Sci. 2017;104:302-14. doi: 10.1016/j.ejps.2017.04.013, PMID 28433750.

Patel N, Nakrani H, Raval M, Sheth N. Development of loteprednol etabonate-loaded cationic nanoemulsified in-situ ophthalmic gel for sustained delivery and enhanced ocular bioavailability. Drug Delivery. 2016;23(9):3712-23. doi: 10.1080/10717544.2016.1223225, PMID 27689408.

Ibrahim MM, Abd-Elgawad AE, Soliman OA, Jablonski MM. Nanoparticle-based topical ophthalmic formulations for sustained celecoxib release. J Pharm Sci. 2013;102(3):1036-53. doi: 10.1002/jps.23417, PMID 23293035.

Lim LT, Ah-Kee EY, Collins CE. Common eye drops and their implications for pH measurements in the management of chemical eye injuries. Int J Ophthalmol. 2014;7(6):1067-8. doi: 10.3980/j.issn.2222-3959.2014.06.29, PMID 25540767.

Baranowski P, Karolewicz B, Gajda M, Pluta J. Ophthalmic drug dosage forms: characterisation and research methods. Sci World J. 2014;2014:861904. doi: 10.1155/2014/861904. PMID 24772038.

Ustünda g-Okur N, Gokce EH, Bozbiyik DI, Egrilmez S, Ozer O, Ertan G. Preparation and in vitro-in vivo evaluation of ofloxacin loaded ophthalmic Nano structured lipid carriers modified with chitosan oligosaccharide lactate for the treatment of bacterial keratitis. Eur J Pharm Sci. 2014;63:204-15.

Pawar P, Kashyap H, Malhotra S, Sindhu R. Hp-β-CD-voriconazole in situ gelling system for ocular drug delivery: in vitro, stability, and antifungal activities assessment. BiomMed Res Int. 2013;2013:341218:341218. doi: 10.1155/2013/341218.

Kurniawansyah IS, Rusdiana T, Wahab HA, Subarnas A. In situ ophthalmic gel with ion activated system. Int J Appl Pharm. 2019;11:15-8.

Majeed A, Khan NA. Ocular in situ gel: an overview. J Drug Delivery Ther. 2019;9(1):337-47. doi: 10.22270/jddt.v9i1.2231.

Bhoyar BS, Agnihotrh VV, Bodhankar MM. A noval thermoreversible phase transition system with flux enhancers for ophthalmic application. Int J Pharm Pharm Sci. 2011;3:367-70.

Published

07-11-2021

How to Cite

KURNIAWANSYAH, I. S., SOPYAN, I., RUSDIANA, T., PRAMASHELA, F. S., & SUBARNAS, A. (2021). A COMPREHENSIVE CHEMICAL CHARACTERIZATION OF IN SITU OPHTHALMIC GEL. International Journal of Applied Pharmaceutics, 13(6), 47–53. https://doi.org/10.22159/ijap.2021v13i6.42457

Issue

Section

Review Article(s)

Most read articles by the same author(s)

1 2 3 4 > >>