FORMULATION AND EVALUATION OF LULICONAZOLE NANOEMULGEL USING BOX-BEHNKEN DESIGN APPROACH
DOI:
https://doi.org/10.22159/ijap.2024v16i6.51522Keywords:
Clove oil, Nanoemulsion, Luliconazole, Carbopol gel, NanoemulgelAbstract
Objective: The present study was aimed to develop and assess a Luliconazole-loaded nano emulgel for topical application.
Methods: Nanoemulsion of Luliconazole was prepared by ultrasonication method. A pseudo-ternary phase diagram was constructed to determine the ideal ratio of oil and the surfactant/co-surfactant mixture for nanoemulsion preparation. The Box Behnken statistical design was utilized to optimize the nanoemulsion. The optimized batch of nanoemulsion was incorporated into the 1% Carbopol gel as nanoemulgel. It was evaluated for various parameters like globule size, zeta potential, pH, spreadability, viscosity, drug content, drug release, ex vivo permeation study, in vivo animal skin irritation study, and histopathology studies.
Results: The optimized formulation showed a globule size of 130.5 nm and entrapment efficiency of 80% and the values were found to be within±5% of predicted values, indicating the suggested statistical model was significant at 95% of confidence interval. The zeta potential of the formulation was found to be-22.1 mV, indicating enhanced stability of the formulation. Transmission Electron Microscopy (TEM) images revealed that the formulation had a smooth surface texture with a mean globule size meeting the nanoscale size range. The drug release study demonstrated a sustained release pattern for the formulation, with a maximum release of 74.93±0.8% over 8 h. The formulated gel exhibited appreciable ex vivo permeability. An in vivo skin irritation test on Wister rats showed no signs of skin irritation from the formulation. The histopathological examination further confirmed that the formulation was dermatologically safe, exhibiting no toxicity or irritation.
Conclusion: The results of the present study concluded that Luliconazole-loaded nanoemulgel could be a potential topical drug delivery approach for the management of fungal infections.
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Koga H, Nanjoh Y, Makimura K, Tsuboi R. In vitro antifungal activities of luliconazole a new topical imidazole. Med Mycol. 2009;47(6):640-7. doi: 10.1080/13693780802541518, PMID 19115136.
Alghaith AF, Alshehri S, Alhakamy NA, Hosny KM. Development optimization and characterization of nanoemulsion loaded with clove oil naftifine antifungal for the management of tinea. Drug Deliv. 2021;28(1):343-56. doi: 10.1080/10717544.2021.1879314, PMID 33517791.
Kumar M, Shanthi N, Mahato AK, Soni S, Rajnikanth PS. Preparation of luliconazole nanocrystals loaded hydrogel for improvement of dissolution and antifungal activity. Heliyon. 2019;5(5):e01688. doi: 10.1016/j.heliyon.2019.e01688, PMID 31193099.
Baghel S, Nair VS, Pirani A, Sravani AB, Bhemisetty B, Ananthamurthy K. Luliconazole loaded nanostructured lipid carriers for topical treatment of superficial tinea infections. Dermatol Ther. 2020;33(6):e13959. doi: 10.1111/dth.13959, PMID 32618400.
Che Marzuki NH, Wahab RA, Abdul Hamid M. An overview of nanoemulsion: concepts of development and cosmeceutical applications. Biotechnol Equip. 2019;33(1):779-97. doi: 10.1080/13102818.2019.1620124.
Bashir M, Ahmad J, Asif M, Khan SU, Irfan M, Y Ibrahim A. Nanoemulgel an innovative carrier for diflunisal topical delivery with profound anti-inflammatory effect: in vitro and in vivo evaluation. Int J Nanomedicine. 2021;16:1457-72. doi: 10.2147/IJN.S294653, PMID 33654396.
Abolmaali SS, Tamaddon AM, Farvadi FS, Daneshamuz S, Moghimi H. Pharmaceutical nanoemulsions and their potential topical and transdermal applications. Ira J Pharm Sci. 2011;7(3):139-50.
Dhawan B, Aggarwal G, Harikumar S. Enhanced transdermal permeability of piroxicam through novel nanoemulgel formulation. Int J Pharm Investig. 2014;4(2):65-76. doi: 10.4103/2230-973X.133053, PMID 25006551.
Ngawhirunpat T, Worachun N, Opanasopit P, Rojanarata T, Panomsuk S. Cremophor RH40-PEG 400 microemulsions as transdermal drug delivery carrier for ketoprofen. Pharm Dev Technol. 2013;18(4):798-803. doi: 10.3109/10837450.2011.627871, PMID 22023398.
Oktay AN, Karakucuk A, Ilbasmis Tamer S, Celebi N. Dermal flurbiprofen nanosuspensions: optimization with design of experiment approach and in vitro evaluation. Eur J Pharm Sci. 2018;122:254-63. doi: 10.1016/j.ejps.2018.07.009, PMID 29981401.
Yang J, Liang Z, LU P, Song F, Zhang Z, Zhou T. Development of a luliconazole nanoemulsion as a prospective ophthalmic delivery system for the treatment of fungal keratitis: in vitro and in vivo evaluation. Pharmaceutics. 2022;14(10):2052. doi: 10.3390/pharmaceutics14102052, PMID 36297487.
Azeem A, Rizwan M, Ahmad FJ, Iqbal Z, Khar RK, Aqil M. Nanoemulsion components screening and selection: a technical note. AAPS Pharm Sci Tech. 2009;10(1):69-76. doi: 10.1208/s12249-008-9178-x, PMID 19148761.
Gao L, Liu G, Wang X, Liu F, XU Y, MA J. Preparation of a chemically stable quercetin formulation using nanosuspension technology. Int J Pharm. 2011;404(1-2):231-7. doi: 10.1016/j.ijpharm.2010.11.009, PMID 21093559.
Mahadev M, Nandini HS, Ramu R, Gowda DV, Almarhoon ZM, Al-Ghorbani M. Fabrication and evaluation of quercetin nanoemulsion: a delivery system with improved bioavailability and therapeutic efficacy in diabetes mellitus. Pharmaceuticals (Basel). 2022 Jan 5;15(1):70. doi: 10.3390/ph15010070, PMID 35056127.
Choudhury H, Zakaria NF, Tilang PA, Tzeyung AS, Pandey M, Chatterjee B. Formulation development and evaluation of rotigotine mucoadhesive nanoemulsion for intranasal delivery. J Drug Deliv Sci Technol. 2019;54:101-30. doi: 10.1016/j.jddst.2019.101301.
Dasgupta S, Dey S, Choudhury S, Mazumder B. Topical delivery of aceclofenac as nanoemulsion comprising excipients having optimum emulsification capabilities: preparation characterization and in vivo evaluation. Expert Opin Drug Deliv. 2013;10(4):411-20. doi: 10.1517/17425247.2013.749234, PMID 23316798.
Liu WH, Liu TC, Mong MC. Antibacterial effects and action modes of asiatic acid. Biomedicine (Taipei). 2015;5(3):16. doi: 10.7603/s40681-015-0016-7, PMID 26280399.
Mahtab A, Anwar M, Mallick N, Naz Z, Jain GK, Ahmad FJ. Transungual delivery of ketoconazole nanoemulgel for the effective management of onychomycosis. AAPS Pharm Sci Tech. 2016;17(6):1477-90. doi: 10.1208/s12249-016-0488-0, PMID 26857516.
Teaima MH, El-messiry HM, Shaker HA, El-nabarawi MA, Helal DA. Optimizing levetiracetam surfactant-based nanovesicles (lev-nvs) gel for treating epilepsy using experimental design. Int J App Pharm. 2023;15(2):194-200. doi: 10.22159/ijap.2023v15i2.46450.
Souto EB, Baldim I, Oliveira WP, Rao R, Yadav N, Gama FM. SLN and NLC for topical dermal and transdermal drug delivery. Expert Opin Drug Deliv. 2020;17(3):357-77. doi: 10.1080/17425247.2020.1727883, PMID 32064958.
Shadab MD, Nabil AA, Aldawsari HM, Kotta S, Ahmad J, Akhter S. Improved analgesic and anti-inflammatory effect of diclofenac sodium by topical nanoemulgel: formulation development in vitro and in vivo studies. J Chem. 2020;2:1-10. doi: 10.1155/2020/4071818.
Srivastava M, Kohli K, Ali M. Formulation development of novel in situ nanoemulgel (NEG) of ketoprofen for the treatment of periodontitis. Drug Deliv. 2016;23(1):154-66. doi: 10.3109/10717544.2014.907842, PMID 24786482.
Mahmoud RA, Hussein AK, Nasef GA, Mansour HF. Oxiconazole nitrate solid lipid nanoparticles: formulation in vitro characterization and clinical assessment of an analogous loaded carbopol gel. Drug Dev Ind Pharm. 2020;46(5):706-16. doi: 10.1080/03639045.2020.1752707, PMID 32266837.
Shukr M, Metwally GF. Evaluation of topical gel bases formulated with various essential oils for antibacterial activity against methicillin-resistant staphylococcus aureus. Trop J Pharm Res. 2013;12(6):877-84. doi: 10.4314/tjpr.v12i6.3.
Laxmi M, Bhardwaj A, Mehta S, Mehta A. Development and characterization of nanoemulsion as carrier for the enhancement of bioavailability of artemether. Artif Cells Nanomed Biotechnol. 2015;43(5):334-44. doi: 10.3109/21691401.2014.887018, PMID 24641773.
El-Leithy ES, Makky AM, Khattab AM, Hussein DG. Nanoemulsion gel of nutraceutical co-enzyme q10 as an alternative to conventional topical delivery system to enhance skin permeability and anti-wrinkle efficiency. Int J Pharm Pharm Sci. 2017;9(10):207-17. doi: 10.22159/ijpps.2017v9i11.21751.
Bansal A, Saleem MA, Imam S, Singh S. Preparation and evaluation of valdecoxib emulgel formulations. Biomed Pharmacol J. 2008;1(1):131-8.
Lokhandwala H, Deshpande A, Deshpande SH. Kinetic modeling and dissolution profile comparison: an overview. Int J Pharm Biol Sci. 2013;4(1):728-33.
Kaur P, Garg, V, Bawa P, Sharma R, Singh SK, Kumar B. Formulation systematic optimization in vitro ex vivo and stability assessment of transethosome based gel of curcumin. Asian J Pharm Clin Res. 2018;11(2):28563. doi: 10.22159/ajpcr.2018.v11s2.28563.
Ritmaleni J, Juson AK, Zulkarnain AK, Indaryanti AE, Fatmawati A. The effect of variation concentration of tetrahydrohexagamavunon-5 (THHGV-5) in emulgel preparation on acute dermal irritation effect and sun protecting factor (SPF) value. Int J App Pharm. 2023;15(6):282-7. doi: 10.22159/ijap.2023v15i6.47741.
Ivar DO Sul JA, Rodrigues O, Santos IR, Fillmann G, Matthiensen A. Skin irritation and histopathologic alterations in rats exposed to lightstick contents UV radiation and seawater. Ecotoxicol Environ Saf. 2009;72(7):2020-4. doi: 10.1016/j.ecoenv.2009.05.006, PMID 19473704.
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