Optimization and Evaluation of Topical Gel Containing Solid Lipid Nanoparticles Loaded with Metronidazole

Author

Ms. Neha Dubey, Dr. Arun Kumar Patel, Dr. Naveen Shivavedi, Mr. Shailendra Patel, Ms. Supriya Ojha


Abstract

 The present research was undertaken to develop, optimize, and evaluate a topical gel containing metronidazole-loaded solid lipid nanoparticles (SLNs) with the objective of improving the topical delivery of metronidazole and providing a suitable sustained-release formulation. Metronidazole is a nitroimidazole antimicrobial agent widely used in the treatment of infections caused by susceptible anaerobic microorganisms and protozoa. Conventional topical formulations may present limitations related to drug retention at the site of application and drug-release characteristics. Solid lipid nanoparticles offer several potential advantages as topical drug-delivery carriers, including nanoscale particle size, enhanced contact with the skin, controlled drug release, and protection of the incorporated drug.

Metronidazole-loaded SLNs were prepared using a suitable lipid-based nanoparticle preparation technique. The formulation was optimized by evaluating critical formulation parameters such as particle size, polydispersity index, zeta potential, entrapment efficiency, drug loading, and percentage yield. The optimized SLN formulation was incorporated into a suitable topical gel base and evaluated for appearance, homogeneity, pH, viscosity, spreadability, drug content, extrudability, and in-vitro drug-release characteristics. The release data were further analyzed using appropriate kinetic models to understand the drug-release mechanism.

The optimized metronidazole-loaded SLN formulation was expected to provide nanosized particles with satisfactory physicochemical characteristics and improved drug-retention/release properties. Incorporation of the optimized SLNs into a topical gel may provide a convenient and potentially effective platform for localized delivery of metronidazole. The developed formulation may therefore represent a promising approach for topical metronidazole delivery, subject to confirmation through appropriate biological and stability studies.



Keywords

Metronidazole, solid lipid nanoparticles, SLN, topical gel, nanoparticulate drug delivery, optimization, controlled release.



Full Text:

Download Paper PDF


References


  1. Abdelbary G, Fahmy RH. Diazepam-loaded solid lipid nanoparticles: design and characterization. Aaps Pharmscitech. 2009 Mar 1;10(1):211-9.
  2. Agarwal A, Agrawal H, Tiwari S, Jain S, Agrawal GP. Cationic ligand appended nanoconstructs: a prospective strategy for brain targeting. International journal of pharmaceutics. 2011 Dec 12;421(1):189-201.
  3. Basha BN, Prakasam K, Goli D. Formulation and evaluation of gel containing fluconazole-antifungal agent. Int J Drug Dev Res. 2011 Oct;3(4):109-28
  4. Singla V, Saini S, Joshi B, Rana AC. Emulgel: A new platform for topical drug delivery. International Journal of Pharma and Bio Sciences. 2012;3(1):485-98.
  5. Bagde A, Patel K, Kutlehria S, Chowdhury N, Singh M. Formulation of topical ibuprofen solid lipid nanoparticle (SLN) gel using hot melt extrusion technique (HME) and determining its anti-inflammatory strength. Drug delivery and translational research. 2019 Mar 28:1-2
  6. Bhalekar MR, Madgulkar AR, Desale PS, Marium G. Formulation of piperine solid lipid nanoparticles (SLN) for treatment of rheumatoid arthritis. Drug development and industrial pharmacy. 2017 Jun 3;43(6):1003-10.
  7. Bhaskar K. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) enriched hydrogels for transdermal delivery of flurbiprofen: formulation, in vitro characterisation, pharmacokinetic and pharmacodynamic studies in animals. International Journal of Biomedical Nanoscience and Nanotechnology. 2010 Jan 1;1(2-4):109-32
  8. Bhaskar K, Mohan CK, Lingam M, Mohan SJ, Venkateswarlu V, Rao YM, Bhaskar K, Anbu J, Ravichandran V. Development of SLN and NLC enriched hydrogels for transdermal delivery of nitrendipine: in vitro and in vivo Drug development and industrial pharmacy. 2009 Jan 1;35(1):98-113.
  9. Badiee, Parisa, and Zahra Hashemizadeh. "Opportunistic invasive fungal infections: diagnosis & clinical management." The Indian journal of medical research 2 (2014): 195.
  10. Bonifaz, Alexandro, and Andrés Tirado-Sánchez. "Cutaneous disseminated and extracutaneous sporotrichosis: current status of a complex disease." Journal of Fungi 1 (2017): 6.
  11. Bräm S, Wolfram E, Recent Advances in Effect-directed Enzyme Assays based on Thin-layer Chromatography, Phytochemical Analsis, 2017; 28(2): 74-86.
  12. Chandira RM, Pradeep PA, Bhowmik D, Chiranjib JB, Tripathi KK, Sampath Kumar KP. Design, development and formulation of antiacne dermatological gel. J Chem Pharm Res. 2010;2(1):401-14.
  13. Dasgupta S, K Ghosh S, Ray S, Mazumder B. Solid lipid nanoparticles (SLNs) gels for topical delivery of aceclofenac in vitro and in vivo Current drug delivery. 2013 Dec 1;10(6):656-66.
  14. Desai, Noopur J., and Dilip G. Maheshwari. "UV spectrophotometric method for the estimation of metronidazolein marketed formulation (lotion)." Pharma Science Monitor 2 (2014): 48-54.
  15. Deshkar SS, Bhalerao SG, Jadhav MS, Shirolkar SV. Formulation and Optimization of Topical Solid Lipid Nanoparticles Based Gel of Dapsone Using Design of Experiment. Pharmaceutical nanotechnology. 2018 Dec 1;6(4):264-75
  16. Di, Li, and Edward H. Kerns. Drug-like properties: concepts, structure design and methods from ADME to toxicity optimization. Academic press, 2015.
  17. Ei-Badry, M., Hassan, M. A., Ibrahim, M. A., and Elsaghir, H. (2013). Performance of poloxamer 407 as hydrophilic carrier on the binary mixtures with nimesulide. Farmacia.
  18. El-Housiny, Shaimaa, et al. "Fluconazole-loaded solid lipid nanoparticles topical gel for treatment of pityriasis versicolor: formulation and clinical study." Drug delivery 1 (2018): 78-90.
  19. El-Housiny S, Shams Eldeen MA, El-Attar YA, Salem HA, Attia D, Bendas ER, El-Nabarawi MA. Fluconazole-loaded solid lipid nanoparticles topical gel for treatment of pityriasis versicolor: formulation and clinical study. Drug delivery. 2018 Jan 1;25(1):78-90.
  20. Ekambaram, P., and Abdul Hasan Sathali, A. (2011). Formulation and evaluation of solid lipid nanoparticles of ramipril. Young Pharm. doi:10.4103/0975-1483.83765.
  21. Ekambaram P, Sathali AA, Priyanka K. Solid lipid nanoparticles: a review. Sci Rev Chem Commun. 2012 Feb;2(1):80-102
  22. Felton T, Troke PF, Hope WW, Tissue penetration of antifungal agents, Clinical Microbiology Reviews, 2014; 27(1): 68-88.
  23. Foldvari M. Non-invasive administration of drugs through the skin: challenges in delivery system design. Pharmaceutical science & technology today. 2000 Dec 1;3(12):417-25.
  24. Gaddam N, Aukunuru J. Systemic delivery of diclofenac sodium after topical application of gels incorporated with drug-loaded solid lipid nanoparticles (SLN). Asian Journal of Pharmaceutical Research and Health Care. 2010;2(2):177-87.
  25. Garse H, Jagtap P, Kadam V. Solid lipid nanoparticles based gel for topical delivery of antifungal agent. International Journal of Pharmaceutical Sciences and Research. 2015 Aug 1;6(8):3571.
  26. Gaur PK, Mishra S, Purohit S. Solid lipid nanoparticles of guggul lipid as drug carrier for transdermal drug delivery. BioMed research international. 2013;2013.
  27. Han F, Li S, Yin R, Shi X, Jia Q. Investigation of nanostructured lipid carriers for transdermal delivery of flurbiprofen. Drug development and industrial pharmacy. 2008 Jan 1;34(4):453-8.
  28. Harde H, Agrawal AK, Katariya M, Kale D, Jain S. Development of a topical adapalene-solid lipid nanoparticle loaded gel with enhanced efficacy and improved skin tolerability. RSC Advances. 2015;5(55):43917-29.
  29. Hosseini, Seyed Mostafa, et al. "Doxycycline-encapsulated solid lipid nanoparticles as promising tool against Brucella melitensis enclosed in macrophage: a pharmacodynamics study on J774A. 1 cell line." Antimicrobial Resistance & Infection Control 1 (2019): 62.
  30. https://pubchem.ncbi.nlm.nih.gov/compound/Stearic-acid
  31. https://pubchem.ncbi.nlm.nih.gov/compound/Sodium-acrylate#section=FDA-
  32. https://pubchem.ncbi.nlm.nih.gov/compound/Luliconazole.
  33. https://reference.medscape.com/drug/luzu-luliconazole-999891#10
  34. https://www.drugbank.ca/drugs/DB11333
  35. https://www.drugbank.ca/drugs/DB08933
  36. https://www.semanticscholar.org/paper/Recent-advances-in-oral-delivery-of-drugs-and-using/b74f5b81ade6cd18889a5b063a54f8342328ab65/figure/0
  37. https://www.webmd.com/drugs/2/drug-165453/luliconazole-topical/details.
  38. Hu FQ, Hong Y, Yuan H. Preparation and characterization of solid lipid nanoparticles containing peptide. International journal of pharmaceutics. 2004 Apr 1;273(1-2):29-35.
  39. Ige, Pradum Pundlikrao, Rohan K. Baria, and Surendra G. Gattani. "Fabrication of fenofibrate nanocrystals by probe sonication method for enhancement of dissolution rate and oral bioavailability." Colloids and Surfaces B: Biointerfaces 108 (2013): 366-373.

Share your valuable work from Social Media Buttons