Design and Evaluation of Eudragit RS-100 Based Itraconazole Nanosuspension for Ophthalmic Application

Author(s): Pravin Pawar*, Anita Duduskar, Swati Waydande

Journal Name: Current Drug Research Reviews
(Formerly Current Drug Abuse Reviews)

Volume 13 , Issue 1 , 2021


Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Background: Poor water soluble compounds are difficult to develop as drug products using conventional formulation techniques.

Objective: In the present study, the potential of Eudragit RS-100 nanosuspension as a new vehicle for the improvement of the delivery of drugs to the intraocular level was investigated.

Methods: Solvent evaporation technique has been employed for nanosuspension preparation. Surfactant concentration and drug to polymer ratio has been optimized using 32 factorial design to achieve desired particle size, entrapment efficiency and percent permeation responses as dependent variables. All the formulations were characterized for particle size, zeta potential, polydispersity index (PDI), Fourier Transform Infrared Spectroscopy (FTIR), Differential scanning calorimetery (DSC), X-ray Diffraction (XRD) analysis, viscosity, antifungal study and Transmission Electron Microscopy (TEM). Secondly, itraconazole eye drop was prepared by using sulfobuty ether-β-cyclodextrin and comparatively studying its antifungal efficacy.

Results: The nanosuspension had a particle size range of 332.7-779.2nm, zeta potential +0.609-16.3, entrapment efficiency 61.32 ± 1.36%-76.34 ± 2.04%. Ex vitro corneal permeability study showed that optimized itraconazole nanosuspension produced higher permeation as compared to the market formulation and Itraconazole eye drop. Moreover, optimized nanosuspension was found as more active against Candida albicans & Aspergillus flavus compared to the market formulation and Itraconazole eye drop.

Conclusion: The nanosuspension approach could be an ideal, promising approach to increase the solubility and dissolution of Itraconazole.

Keywords: Itraconazole, eudragit RS-100, nanosuspension, ex-vivo transconeal permeation, pertinent, solvent evaporation.

[1]
Kassem MA, Abdel Rahman AA, Ghorab MM, Ahmed MB, Khalil RM. Nanosuspension as an ophthalmic delivery system for certain glucocorticoid drugs. Int J Pharm 2007; 340(1-2): 126-33.
[http://dx.doi.org/10.1016/j.ijpharm.2007.03.011] [PMID: 17600645]
[2]
Swamy N, Zaheer A, Kumar S. Eudragit RS 100 nanosuspension for the controlled ophthalmic delivery of diclofenac sodium. Thaiphesatchasan 2013; 37: 157-9.
[3]
Higaki S, Myles ME, Loutsch JM, Hill JM. Ophthalmic Drug Delivery Systems. 2nd ed. New York: Marcel Dekker 2003; pp. 309-34.
[http://dx.doi.org/10.1201/9780203912072.ch10]
[4]
Losa C, Calvo P, Castro E, Vila-Jato JL, Alonso MJ. Improvement of ocular penetration of amikacin sulphate by association to poly(butylcyanoacrylate) nanoparticles. J Pharm Pharmacol 1991; 43(8): 548-52.
[http://dx.doi.org/10.1111/j.2042-7158.1991.tb03534.x] [PMID: 1681069]
[5]
Ammar HO, Salama HA, Ghorab M, Mahmoud AA. Nanoemulsion as a potential ophthalmic delivery system for dorzolamide hydrochloride. AAPS PharmSciTech 2009; 10(3): 808-19.
[http://dx.doi.org/10.1208/s12249-009-9268-4] [PMID: 19536653]
[6]
Katzer T, Chaves P, Bernardi A, Pohlmann A, Guterres SS, Ruver Beck RC. Prednisolone-loaded nanocapsules as ocular drug delivery system: Development, in vitro drug release and eye toxicity. J Microencapsul 2014; 31(6): 519-28.
[http://dx.doi.org/10.3109/02652048.2013.879930] [PMID: 24697184]
[7]
Shen Y, Tu J. Preparation and ocular pharmacokinetics of ganciclovir liposomes. AAPS J 2007; 9(3): E371-7.
[http://dx.doi.org/10.1208/aapsj0903044] [PMID: 18170984]
[8]
Cortesi R, Argnani R, Esposito E, et al. Cationic liposomes as potential carriers for ocular administration of peptides with anti-herpetic activity. Int J Pharm 2006; 317(1): 90-100.
[http://dx.doi.org/10.1016/j.ijpharm.2006.02.050] [PMID: 16600535]
[9]
Mudgil M, Pawar PK. Preparation and in vitro/ex vivo evaluation of moxifloxacin-Loaded PLGA nanosuspension for ophthalmic application. Sci Pharm 2013; 81(2): 591-606.
[http://dx.doi.org/10.3797/scipharm.1204-16] [PMID: 23833723]
[10]
Muller G, Kara N, Silvestre R, Castro D. Antifungals in eye infections: Drugs and routes of administration. Rev Bras Oftalmol 2013; 72: 132-41.
[11]
ElMeshad AN, Mohsen AM. Enhanced corneal permeation and antimycotic activity of itraconazole against Candida albicans via a novel nanosystem vesicle. Drug Deliv 2016; 23(7): 2115-23.
[PMID: 25080226]
[12]
Das S, Suresh PK. Nanosuspension: a new vehicle for the improvement of the delivery of drugs to the ocular surface. Application to amphotericin B. Nanomedicine (Lond) 2011; 7(2): 242-7.
[http://dx.doi.org/10.1016/j.nano.2010.07.003] [PMID: 20692375]
[13]
Kumar N, Shishu , Bansal G, Kumar S, Jana AK. Ditosylate salt of itraconazole and dissolution enhancement using cyclodextrins. AAPS PharmSciTech 2012; 13(3): 863-74.
[http://dx.doi.org/10.1208/s12249-012-9804-5] [PMID: 22669594]
[14]
Pignatello R, Bucolo C, Ferrara P, Maltese A, Puleo A, Puglisi G. Eudragit RS100 nanosuspensions for the ophthalmic controlled delivery of ibuprofen. Eur J Pharm Sci 2002; 16(1-2): 53-61.
[http://dx.doi.org/10.1016/S0928-0987(02)00057-X] [PMID: 12113891]
[15]
Pignatello R, Bucolo C, Puglisi G. Ocular tolerability of Eudragit RS100 and RL100 nanosuspensions as carriers for ophthalmic controlled drug delivery. J Pharm Sci 2002; 91(12): 2636-41.
[http://dx.doi.org/10.1002/jps.10227] [PMID: 12434408]
[16]
Castelli F, Messina C, Sarpietro MG, Pignatello R, Puglisi G. Flurbiprofen release from Eudragit RS and RL aqueous nanosuspensions: a kinetic study by DSC and dialysis experiments. AAPS PharmSciTech 2002; 3(2): E9.
[http://dx.doi.org/10.1208/pt030209] [PMID: 12916946]
[17]
Pignatello R, Ricupero N, Bucolo C, Maugeri F, Maltese A, Puglisi G. Preparation and characterization of Eudragit Retard nanosuspensions for the ocular delivery of cloricromene. AAPS PharmSciTech 2006; 7(1): E192-8.
[http://dx.doi.org/10.1208/pt070127] [PMID: 28290042]
[18]
Adibkia K, Siahi Shadbad MR, Nokhodchi A, et al. Piroxicam nanoparticles for ocular delivery: Physicochemical characterization and implementation in endotoxin-induced uveitis. J Drug Target 2007; 15(6): 407-16.
[http://dx.doi.org/10.1080/10611860701453125] [PMID: 17613659]
[19]
Adibkia K, Omidi Y, Siahi MR, et al. Inhibition of endotoxin-induced uveitis by methylprednisolone acetate nanosuspension in rabbits. J Ocul Pharmacol Ther 2007; 23(5): 421-32.
[http://dx.doi.org/10.1089/jop.2007.0039] [PMID: 17900230]
[20]
Das S, Suresh PK, Desmukh R. Design of Eudragit RL 100 nanoparticles by nanoprecipitation method for ocular drug delivery. Nanomedicine (Lond) 2010; 6(2): 318-23.
[http://dx.doi.org/10.1016/j.nano.2009.09.002] [PMID: 19800990]
[21]
Mandal B, Alexander KS, Riga AT. Sulfacetamide loaded Eudragit® RL100 nanosuspension with potential for ocular delivery. J Pharm Pharm Sci 2010; 13(4): 510-23.
[http://dx.doi.org/10.18433/J3SW2T] [PMID: 21486528]
[22]
de Campos AM, Diebold Y, Carvalho EL, Sánchez A, Alonso MJ. Chitosan nanoparticles as new ocular drug delivery systems: In vitro stability, in vivo fate, and cellular toxicity. Pharm Res 2004; 21(5): 803-10.
[http://dx.doi.org/10.1023/B:PHAM.0000026432.75781.cb] [PMID: 15180338]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 13
ISSUE: 1
Year: 2021
Published on: 29 September, 2020
Page: [36 - 48]
Pages: 13
DOI: 10.2174/2589977512666200929111952
Price: $65

Article Metrics

PDF: 284
HTML: 1
EPUB: 1
PRC: 1