Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

Moxifloxacin Hydrochloride-Loaded Eudragit® RL 100 and Kollidon® SR Based Nanoparticles: Formulation, In vitro Characterization and Cytotoxicity

Author(s): Gülsel Yurtdaş Kırımlıoğlu*, Sinan Özer, Gülay Büyükköroğlu and Yasemin Yazan

Volume 24, Issue 3, 2021

Published on: 28 April, 2020

Page: [328 - 341] Pages: 14

DOI: 10.2174/1386207323666200428091945

Price: $65

Abstract

Background: Considering the low ocular bioavailability of conventional formulations used for ocular bacterial infection treatment, there is a need to design efficient novel drug delivery systems that may enhance precorneal retention time and corneal permeability.

Aim and Objective: The current research focuses on developing nanosized and non-toxic Eudragit® RL 100 and Kollidon® SR nanoparticles loaded with moxifloxacin hydrochloride (MOX) for its prolonged release to be promising for effective ocular delivery.

Methods: In this study, MOX incorporation was carried out by spray drying method aiming ocular delivery. In vitro characteristics were evaluated in detail with different methods.

Results: MOX was successfully incorporated into Eudragit® RL 100 and Kollidon® SR polymeric nanoparticles by a spray-drying process. Particle size, zeta potential, entrapment efficiency, particle morphology, thermal, FTIR, NMR analyses and MOX quantification using HPLC method were carried out to evaluate the nanoparticles prepared. MOX loaded nanoparticles demonstrated nanosized and spherical shape while in vitro release studies demonstrated modified-release pattern, which followed the Korsmeyer-Peppas kinetic model. Following the successful incorporation of MOX into the nanoparticles, the formulation (MOX: Eudragit® RL 100, 1:5) (ERL-MOX 2) was selected for further studies because of its better characteristics like cationic zeta potential, smaller particle size, narrow size distribution and more uniform prolonged release pattern. Moreover, ERLMOX 2 formulation remained stable for 3 months and demonstrated higher cell viability values for MOX.

Conclusion: In vitro characterization analyses showed that non-toxic, nano-sized and cationic ERL-MOX 2 formulation has the potential of enhancing ocular bioavailability.

Keywords: Moxifloxacin hydrochloride, nanoparticle, Eudragit® RL 100, Kollidon® SR, modified release, ocular delivery.

[1]
Nagarwal, R.C.; Kant, S.; Singh, P.N.; Maiti, P.; Pandit, J.K. Polymeric nanoparticulate system: a potential approach for ocular drug delivery. J. Control. Release, 2009, 136(1), 2-13.
[http://dx.doi.org/10.1016/j.jconrel.2008.12.018] [PMID: 19331856]
[2]
Pignatello, R.; Ferro, M.; Puglisi, G. Preparation of solid dispersions of nonsteroidal anti-inflammatory drugs with acrylic polymers and studies on mechanisms of drug-polymer interactions. AAPS PharmSciTech, 2002, 3(2)E10
[http://dx.doi.org/10.1208/pt030210] [PMID: 12916947]
[3]
Agnihotri, S.M.; Vavia, P.R. Diclofenac-loaded biopolymeric nanosuspensions for ophthalmic application. Nanomedicine (Lond.), 2009, 5(1), 90-95.
[http://dx.doi.org/10.1016/j.nano.2008.07.003] [PMID: 18823824]
[4]
De Campos, A.M.; Sánchez, A.; Alonso, M.J. Chitosan nanoparticles: a new vehicle for the improvement of the delivery of drugs to the ocular surface. Application to cyclosporin A. Int. J. Pharm., 2001, 224(1-2), 159-168.
[http://dx.doi.org/10.1016/S0378-5173(01)00760-8] [PMID: 11472825]
[5]
Başaran, E.; Demirel, M.; Sirmagül, B.; Yazan, Y. Cyclosporine-A incorporated cationic solid lipid nanoparticles for ocular delivery. J. Microencapsul., 2010, 27(1), 37-47.
[http://dx.doi.org/10.3109/02652040902846883] [PMID: 19545226]
[6]
Mahor, A.; Prajapati, S.K.; Verma, A.; Gupta, R.; Iyer, A.K.; Kesharwani, P. Moxifloxacin loaded gelatin nanoparticles for ocular delivery: Formulation and in-vitro, in-vivo evaluation. J. Colloid Interface Sci., 2016, 483, 132-138.
[http://dx.doi.org/10.1016/j.jcis.2016.08.018] [PMID: 27552421]
[7]
Deschênes, J.; Blondeau, J. Besifloxacin in the management of bacterial infections of the ocular surface. Can. J. Ophthalmol., 2015, 50(3), 184-191.
[http://dx.doi.org/10.1016/j.jcjo.2014.12.013] [PMID: 26040217]
[8]
Başaran, E. Ocular application of dirithromycin incorporated polymeric nanoparticles: an in vitro evaluation. Turk. J. Pharm. Sci., 2017, 14(2), 191-200.
[http://dx.doi.org/10.4274/tjps.69855]
[9]
Bourcier, T.; Thomas, F.; Borderie, V.; Chaumeil, C.; Laroche, L. Bacterial keratitis: predisposing factors, clinical and microbiological review of 300 cases. Br. J. Ophthalmol., 2003, 87(7), 834-838.
[http://dx.doi.org/10.1136/bjo.87.7.834] [PMID: 12812878]
[10]
Constantinou, M.; Daniell, M.; Snibson, G.R.; Vu, H.T.; Taylor, H.R. Clinical efficacy of moxifloxacin in the treatment of bacterial keratitis: a randomized clinical trial. Ophthalmology, 2007, 114(9), 1622-1629.
[http://dx.doi.org/10.1016/j.ophtha.2006.12.011] [PMID: 17822972]
[11]
Diamond, J.P.; White, L.; Leeming, J.P.; Bing Hoh, H.; Easty, D.L. Topical 0.3% ciprofloxacin, norfloxacin, and ofloxacin in treatment of bacterial keratitis: a new method for comparative evaluation of ocular drug penetration. Br. J. Ophthalmol., 1995, 79(6), 606-609.
[http://dx.doi.org/10.1136/bjo.79.6.606] [PMID: 7626579]
[12]
Kaskoos, R.A. Investigation of moxifloxacin loaded chitosan-dextran nanoparticles for topical instillation into eye: In-vitro and ex-vivo evaluation. Int. J. Pharm. Investig., 2014, 4(4), 164-173.
[http://dx.doi.org/10.4103/2230-973X.143114] [PMID: 25426437]
[13]
Srinivas, P.; Pragna, S. Formulation and evaluation of moxifloxacin hydrochloride ocular nanoparticles. Int. J. Nanodimens., 2012, 3(2), 105-113.
[14]
Sabitha, K.; Sajeeth, C.I.; Santhi, K. Chitosan nanoparticles: A novel vehicle for the enhanced ocular delivery of moxifloxacin HCl. Res. J. Pharm. Biol. Chem. Sci., 2012, 3(2), 534-548.
[15]
Singh, G.; Pai, R.S. Atazanavir-loaded Eudragit RL 100 nanoparticles to improve oral bioavailability: optimization and in vitro/in vivo appraisal. Drug Deliv., 2016, 23(2), 532-539.
[http://dx.doi.org/10.3109/10717544.2014.930760] [PMID: 24963752]
[16]
Katara, R.; Majumdar, D.K. Eudragit RL 100-based nanoparticulate system of aceclofenac for ocular delivery. Colloids Surf. B Biointerfaces, 2013, 103, 455-462.
[http://dx.doi.org/10.1016/j.colsurfb.2012.10.056] [PMID: 23261566]
[17]
Das, S.; Suresh, P.K.; Desmukh, R. Design of Eudragit RL 100 nanoparticles by nanoprecipitation method for ocular drug delivery. Nanomedicine (Lond.), 2010, 6(2), 318-323.
[http://dx.doi.org/10.1016/j.nano.2009.09.002] [PMID: 19800990]
[18]
Kolter, K.; Karl, M.; Gryzcke, A. Hot-melt extrusion with BASH Pharma PolymersBASF SE Pharma Ingredients & Services: Ludwingshafen,,2012
[19]
Mansour, H.M.; Sohn, M.; Al-Ghananeem, A.; Deluca, P.P. Materials for pharmaceutical dosage forms: molecular pharmaceutics and controlled release drug delivery aspects. Int. J. Mol. Sci., 2010, 11(9), 3298-3322.
[http://dx.doi.org/10.3390/ijms11093298] [PMID: 20957095]
[20]
Sakr, W.; Alanazi, F.; Sakr, A. Effect of Kollidon® SR on the release of Albuterol Sulphate from matrix tablets. Saudi Pharm. J., 2011, 19(1), 19-27.
[http://dx.doi.org/10.1016/j.jsps.2010.11.002] [PMID: 24115901]
[21]
Arias, J.L.; Gómez-Gallo, A.; Delgado, A.V.; Gallardo, V. Study of the stability of Kollidon® SR suspensions for pharmaceutical applications. Colloids Surf. A Physicochem. Eng. Asp., 2009, 338, 107-113.
[http://dx.doi.org/10.1016/j.colsurfa.2009.01.001]
[22]
Sultana, N.; Akhtar, M.; Shamim, S.; Gul, S. Simultaneous determination of moxifloxacin and H2 receptor antagonist in pharmaceutical dosage formulations by RP-HPLC: application to in vitro drug interactions. Quim. Nova, 2011, 34(4), 683-688.
[http://dx.doi.org/10.1590/S0100-40422011000400022]
[23]
Sharma, U.K.; Verma, A.; Prajapati, S.K.; Pandey, H.; Pandey, A.C. In vitro, in vivo and pharmacokinetic assessment of amikacin sulphate laden polymeric nanoparticles meant for controlled ocular drug delivery. Appl. Nanosci., 2015, 5, 143-155.
[http://dx.doi.org/10.1007/s13204-014-0300-y]
[24]
Yurtdaş-Kırımlıoğlu, G.; Özer, S.; Büyükköroğlu, G.; Yazan, Y. Formulation and in vitro evaluation of moxifloxacin hydrochloride-loaded polymeric nanoparticles for ocular application. Lat. Am. J. Pharm., 2018, 37(9), 1850-1862.
[25]
Zhang, Y.; Huo, M.; Zhou, J.; Zou, A.; Li, W.; Yao, C.; Xie, S. DDSolver: an add-in program for modeling and comparison of drug dissolution profiles. AAPS J., 2010, 12(3), 263-271.
[http://dx.doi.org/10.1208/s12248-010-9185-1] [PMID: 20373062]
[26]
Mosmann, T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods, 1983, 65(1-2), 55-63.
[http://dx.doi.org/10.1016/0022-1759(83)90303-4] [PMID: 6606682]
[27]
Patel, A.; Cholkar, K.; Agrahari, V.; Mitra, A.K. Ocular drug delivery systems: An overview. World J. Pharmacol., 2013, 2(2), 47-64.
[http://dx.doi.org/10.5497/wjp.v2.i2.47] [PMID: 25590022]
[28]
Lopedota, A.; Trapani, A.; Cutrignelli, A.; Chiarantini, L.; Pantucci, E.; Curci, R.; Manuali, E.; Trapani, G. The use of Eudragit RS 100/cyclodextrin nanoparticles for the transmucosal administration of glutathione. Eur. J. Pharm. Biopharm., 2009, 72(3), 509-520.
[http://dx.doi.org/10.1016/j.ejpb.2009.02.013] [PMID: 19281845]
[29]
Radomska-Soukharev, A. Stability of lipid excipients in solid lipid nanoparticles. Adv. Drug Deliv. Rev., 2007, 59(6), 411-418.
[http://dx.doi.org/10.1016/j.addr.2007.04.004] [PMID: 17553589]
[30]
Sunkara, G.; Kompella, U.B. Membrane transport processes in the eye.Ophthalmic Drug Delivery Systems; Mitra, A.K., Ed.; Marcel Dekker: New York, 2003, pp. 13-58.
[http://dx.doi.org/10.1201/9780203912072.ch2]
[31]
Yenilmez, E.; Yurtdaş-Kırımlıoğlu, G.; Şenel, B.; Başaran, E. Preparation, characterization and in vitro evaluation of dirithromycin loaded Eudragit® RS 100 nanoparticles for topical application. Lat. Am. J. Pharm., 2017, 36(11), 2203-2212.
[32]
Araújo, J.; Gonzalez, E.; Egea, M.A.; Garcia, M.L.; Souto, E.B. Nanomedicines for ocular NSAIDs: safety on drug delivery. Nanomedicine (Lond.), 2009, 5(4), 394-401.
[http://dx.doi.org/10.1016/j.nano.2009.02.003] [PMID: 19341814]
[33]
Yurtdaş-Kırımlıoğlu, G.; Yazan, Y. Formulation and in vitro characterization of polymeric nanoparticles designed for oral delivery of levofloxacin hemihydrate. Eur. Int. J. Sci. Tech., 2016, 5(4), 148-157.
[34]
Sormoli, M.E.; Islam, M.I.U.; Langrish, T.A.G. The effect of chitosan hydrogen bonding on lactose crystallinity during spray drying. J. Food Eng., 2012, 108, 541-548.
[http://dx.doi.org/10.1016/j.jfoodeng.2011.09.011]
[35]
Adibkia, K.; Javadzadeh, Y.; Dastmalchi, S.; Mohammadi, G.; Niri, F.K.; Alaei-Beirami, M. Naproxen-eudragit RS100 nanoparticles: preparation and physicochemical characterization. Colloids Surf. B Biointerfaces, 2011, 83(1), 155-159.
[http://dx.doi.org/10.1016/j.colsurfb.2010.11.014] [PMID: 21130612]
[36]
Anuradha, M.S.; Saritha, A. Formulation and evaluation of controlled release ocular inserts containing moxifloxacin hydrochloride. Am. J. PharmTech. Res., 2014, 4(1), 101-114.
[37]
Yurtdaş Kırımlıoğlu, G.; Menceloğlu, Y.; Erol, K.; Yazan, Y. In vitro/in vivo evaluation of gamma-aminobutyric acid-loadedN,N-dimethylacrylamide-based pegylated polymeric nanoparticles for brain delivery to treat epilepsy. J. Microencapsul., 2016, 33(7), 625-635.
[http://dx.doi.org/10.1080/02652048.2016.1234515] [PMID: 27606701]
[38]
Devi, T.S.R.; Gayatahri, S. FTIR and FT-RAMAN Spectral Analysis of Paclitaxel Drugs. IJPSR, 2010, 2, 106-110.
[39]
Pawar, P.K.; Katara, R.; Majumdar, D.K. Design and evaluation of moxifloxacin hydrochloride ocular inserts. Acta Pharm., 2012, 62(1), 93-104.
[http://dx.doi.org/10.2478/v10007-012-0002-5] [PMID: 22472452]
[40]
Eudragit, RL RS 100. http://www.higuchiinc.co.jb/pharma/excipient/eudragit/pdf/detail_e udragitRLRS.pdf\ [Accessed October 1, 2016]
[41]
Kapse, S.V.; Gaikwad, R.V.; Samad, A.; Devarajan, P.V. Self nanoprecipitating preconcentrate of tamoxifen citrate for enhanced bioavailability. Int. J. Pharm., 2012, 429(1-2), 104-112.
[http://dx.doi.org/10.1016/j.ijpharm.2012.02.042] [PMID: 22414426]
[42]
ICH. Q2B 1996. Validation of Analytical Procedures: Methodology (CPMP/ICH/281/95) - ICH Harmonized Tripartite Guideline, The European Agency for the Evaluation of Medicinal Products, Step 4, Consensus Guideline Proceedings of the International Conference on Harmonization, Geneva 1996, pp. 1-10..
[43]
Thagele, R.; Mishra, A.; Pathak, A.K. Formulation and characterization of clarithromycin based nanoparticulate drug delivery system. Int. J. Pharm. Life Sci., 2011, 2, 510-515.
[44]
Mudgil, M.; Pawar, P.K. Preparation and in vitro/ex vivo evaluation of moxifloxacin-loaded PLGA nanosuspensions for ophthalmic application. Sci. Pharm., 2013, 81(2), 591-606.
[http://dx.doi.org/10.3797/scipharm.1204-16] [PMID: 23833723]
[45]
Zuo, J.; Gao, Y.; Bou-Chacra, N.; Löbenberg, R. Evaluation of the DDSolver Software Applications. Biomed. Res. Int. Article, 2014, ID204925, 1-9.
[46]
Dash, S.; Murthy, P.N.; Nath, L.; Chowdhury, P. Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol. Pharm., 2010, 67(3), 217-223.
[PMID: 20524422]
[47]
Loveymi, B.D.; Jelvehgari, M.; Zakeri-Milani, P.; Valizadeh, H. Design of vancomycin RS-100 nanoparticles in order to increase the intestinal permeability. Adv. Pharm. Bull., 2012, 2(1), 43-56.
[PMID: 24312770]
[48]
Honary, S.; Zahir, F. Effect of zeta potential on the properties of nano-drug delivery systems-A review (Part1). Trop. J. Pharm. Res., 2013, 12(2), 255-264.
[49]
Kaş, H.S. Partikül büyüklüğü ve partikül büyüklük dağılımı.Farmasötik Teknoloji, 2nd ed; Gürsoy, A.Z., Ed.; Aktif Matbaav Reklam Himetleri: İstanbul, 2012, pp. 69-84.
[50]
Li, W.; Zhou, J.; Xu, Y. Study of the in vitro cytotoxicity testing of medical devices. Biomed. Rep., 2015, 3(5), 617-620.
[http://dx.doi.org/10.3892/br.2015.481] [PMID: 26405534]
[51]
Yurtdaş-Kırımlıoğlu, G.; Görgülü, Ş. Design and characterization of montelukast sodium loaded Kollidon® SR nanoparticles and evaluation of release kinetics and cytotoxicity potential. Lat. Am. J. Pharm., 2019, 38(7), 1350-1360.
[52]
Öztürk, A.A.; Yenilmez, E.; Arslan, R.; Şenel, B.; Yazan, Y. Dexketoprofen trometamol-loaded Kollidon SR and Eudragit RS 100 nanoparticles: Formulation and in vitro-in vivo evaluation. Lat. Am. J. Pharm., 2017, 36(11), 2153-2165.
[53]
Aksungur, P.; Demirbilek, M.; Denkbaş, E.B.; Vandervoort, J.; Ludwig, A.; Unlü, N. Development and characterization of Cyclosporine A loaded nanoparticles for ocular drug delivery: Cellular toxicity, uptake, and kinetic studies. J. Control. Release, 2011, 151(3), 286-294.
[http://dx.doi.org/10.1016/j.jconrel.2011.01.010] [PMID: 21241752]
[54]
Coradeghini, R.; Gioria, S.; García, C.P.; Nativo, P.; Franchini, F.; Gilliland, D.; Ponti, J.; Rossi, F. Size-dependent toxicity and cell interaction mechanisms of gold nanoparticles on mouse fibroblasts. Toxicol. Lett., 2013, 217(3), 205-216.
[http://dx.doi.org/10.1016/j.toxlet.2012.11.022] [PMID: 23246733]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy