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    Ketoconazole Nanocrystals Fortified Gel for Improved Transdermal Applications

    • Bhavin Vadher
    • Sunny Shah
    • Kiran Dudhat
    • Mori Dhaval
    • Sudarshan Sing
    • Bhupendra G Prajapati


    Abstract

    Ketoconazole (KTZ) is a commonly prescribed antifungal drug used to treat several tropical and systemic fungus infections. The topical bioavailability of KTZ is limited due to extremely low water solubility and high molecular weight. The present investigation aimed to develop a ketoconazole nanocrystals formulation to improve the biomimetic attributes. The ketoconazole nanocrystals were prepared using a top-down media milling technique with a size of less than 800 nm and a narrow polydispersity index (PDI) of 0.434. The simplex lattice design was used to further investigate the effect of change in the proportion of different stabilizers on critical product attributes such as particle size and PDI. The result of the in vitro drug release and anti-fungal study proved the superiority of the optimized KTZ nanocrystal in inhibiting fungal infection and suspension of pure drug. The optimized nanocrystals entrapped within Carbopol-934P gel had higher permeability through cellulose membrane compared, to the marketed product (2 % ketoconazole % w/w Ketodoc Cream®) with sustained release for 24 h. Moreover, the release profile indicated diffusion-controlled release from gel following Korsmeyer-Peppas. The present investigation successfully demonstrated the application of simplex lattice design and desirability function in optimizing ketoconazole nanocrystals to improve its transdermal application.

    Section

    References

    1. Mittal, A., Raber, A.S., Lehr, C.M., Hansen, S. (2013). Particle based vaccine formulations for transcuta-neous immunization, Human Vaccines and Immunotherapeutics, 9, 1950-1955.
    2. Bodratti, A. M., and Alexandridis, P. (2018). Formulation of poloxamers for drug delivery. Journal of functional biomaterials, 9(1), 11.
    3. Chi Lip Kwok, P., and Chan, H. K. (2014). Nanotechnology versus other techniques in improving drug dissolution. Current pharmaceutical design, 20(3), 474-482.
    4. Chittasupho, C., Ditsri, S., Singh, S., Kanlayavattanakul, M., Duangnin, N., Ruksiriwanich, W., Athi-komkulchai, S. (2022) Ultraviolet Radiation Protective and Anti-Inflammatory Effects of Kaempferia galanga L. rhizome oil and microemulsion: formulation, characterization, and hydrogel prepara-tion. Gels, 8, 639. https://doi.org/10.3390/gels8100639
    5. Chittasupho, C., Chaobankrang, K., Sarawungkad, A., Samee, W., Singh, S., Hemsuwimon, K., Okonogi, S., Kheawfu, K., Kiattisin, K., Chaiyana, W. (2023) Antioxidant, anti-inflammatory and attenuating intra-cellular reactive oxygen species activities of Nicotiana tabacum var. Virginia leaf extract phytosomes and shape memory gel formulation. Gels 9, 78. https://doi.org/10.3390/gels9020078
    6. Dai, W. G., Dong, L. C., Li, S., and Deng, Z. (2008). Combination of Pluronic/Vitamin E TPGS as a poten-tial inhibitor of drug precipitation. International journal of pharmaceutics, 355(1-2), 31-37.
    7. Dong, Y., Ng, W. K., Shen, S., Kim, S., and Tan, R. B. (2009). Preparation and characterization of spirono-lactone nanoparticles by antisolvent precipitation. International journal of pharmaceutics, 375(1-2), 84-88.
    8. Effendy, I., and Maibach, H. I. (1995). Surfactants and experimental irritant contact dermatitis. Contact dermatitis, 33(4), 217-225.
    9. Hiendrawan, S., Hartanti, A. W., Veriansyah, B., Widjojokusumo, E. D. W. A. R. D., and Tjandrawinata, R. R. (2015). Solubility enhancement of ketoconazole via salt and cocrystal formation. Int J Pharm Pharm Sci, 7(7), 160-164.
    10. Hintz, R. J., Johnson, K. C. (1989). The effect of particle size distribution on dissolution rate and oral ab-sorption. International Journal of Pharmaceutics, 51(1), 9-17.
    11. Jacobs, G. A., Gerber, M., Malan, M. M., Du Preez, J. L., Fox, L. T., and Du Plessis, J. (2016). Topical de-livery of acyclovir and ketoconazole. Drug delivery, 23(2), 631-641.
    12. Kolašinac, N., Kachrimanis, K., Homšek, I., Grujić, B., Đurić, Z., and Ibrić, S. (2012). Solubility enhance-ment of desloratadine by solid dispersion in poloxamers. International journal of pharmaceutics, 436(1-2), 161-170.
    13. Koutsoukos, P. G., and Valsami‐Jones, E. (2006). Principles of phosphate dissolution and precipita-tion. ChemInform, 37(12).
    14. Lademann, J., Richter, H., Teichmann, A., Otberg, N., Blume-Peytavi, U., Luengo, J., Barbara Weiß, B., Schaefer, F. U., Lehr, M.C., Wepf, R., and Sterry, W. (2007). Nanoparticles–an efficient carrier for drug delivery into the hair follicles. European Journal of Pharmaceutics and Biopharmaceutics, 66(2), 159-164.
    15. Li, Y., Wang, D., Lu, S., Zeng, L., Wang, Y., Song, W., and Liu, J. (2018). Pramipexole nanocrystals for transdermal permeation: Characterization and its enhancement micro-mechanism. European Journal of Pharmaceutical Sciences, 124, 80-88.
    16. Mahtab, A., Anwar, M., Mallick, N., Naz, Z., Jain, G. K., and Ahmad, F. J. (2016). Transungual delivery of ketoconazole nanoemulgel for the effective management of onychomycosis. AAPS PharmSciTech, 17, 1477-1490.
    17. Müller, R. H., and Jacobs, C. (2002). Buparvaquone mucoadhesive nanosuspension: preparation, optimi-sation and long-term stability. International journal of pharmaceutics, 237(1-2), 151-161.
    18. Muller, R. H., Becker, R., Kruss, B., and Peters, K. (1999). U.S. Patent No. 5,858,410. Washington, DC: U.S. Patent and Trademark Office.
    19. Müller, R. H., Gohla, S., and Keck, C. M. (2011). State of the art of nanocrystals–special features, produc-tion, nanotoxicology aspects and intracellular delivery. European journal of pharmaceutics and bio-pharmaceutics, 78(1), 1-9.
    20. Müller, R. H., Mäder, K., and Gohla, S. (2000). Solid lipid nanoparticles (SLN) for controlled drug deliv-ery–a review of the state of the art. European journal of pharmaceutics and biopharmaceutics, 50(1), 161-177.
    21. Nisha T., Sivakumar A., Amitava M., Chandrasekaran N. (2018). Enhanced antifungal activity of Keto-conazole using rose oil based novel microemulsion formulation. Journal of Drug Delivery Science and Technology, 47, 434-444.
    22. Ochi, M., Kawachi, T., Toita, E., Hashimoto, I., Yuminoki, K., Onoue, S., and Hashimoto, N. (2014). De-velopment of nanocrystal formulation of meloxicam with improved dissolution and pharmacokinetic behaviors. International journal of pharmaceutics, 474(1-2), 151-156.
    23. Ontong, J.C., Singh, S., Nwabor, O.F. Chusri S., Voravuthikunchai, S.P. (2020). Potential of antimicrobial topical gel with synthesized biogenic silver nanoparticle using Rhodomyrtus tomentosa leaf extract and silk sericin. Biotechnol Lett 42, 2653–2664. https://doi.org/10.1007/s10529-020-02971-5
    24. Patel, M. R., Patel, R. B., Parikh, J. R., Solanki, A. B., and Patel, B. G. (2011). Investigating effect of mi-croemulsion components: in vitro permeation of ketoconazole. Pharmaceutical development and technology, 16(3), 250-258.
    25. Patel, V., Sharma, O. P., and Mehta, T. (2018). Nanocrystal: A novel approach to overcome skin barriers for improved topical drug delivery. Expert opinion on drug delivery, 15(4), 351-368
    26. Patzelt, A., Richter, H., Knorr, F., Schäfer, U., Lehr, C. M., Dähne, L., and Lademann, J. (2011). Selective follicular targeting by modification of the particle sizes. Journal of controlled release, 150(1), 45-48.
    27. Pelikh, O., Stahr, P. L., Huang, J., Gerst, M., Scholz, P., Dietrich, H., Natalie, G., and Keck, C. M. (2018). Nanocrystals for improved dermal drug delivery. European Journal of Pharmaceutics and Biopharma-ceutics, 128, 170-178.
    28. Ramzan, M., Gourion-Arsiquaud, S., Hussain, A., Gulati, J. S., Zhang, Q., Trehan, S., and Kaur, I. P. (2022). In vitro release, ex vivo penetration, and in vivo dermatokinetics of ketoconazole-loaded solid lipid nanoparticles for topical delivery. Drug Delivery and Translational Research, 1-25.
    29. Reddy, M. S., Mutalik, S., and Rao, G. V. (2006). Preparation and Evaluation of Minoxidil Gels for Topical Application in Alopecia opical Application in Alopecia. Indian journal of pharmaceutical sciences, 432.
    30. Sadozai, S. K., Khan, S. A., Baseer, A., Ullah, R., Zeb, A., and Schneider, M. (2022). In vitro, ex vivo, and in vivo evaluation of nanoparticle-based topical formulation against candida albicans infection. Fron-tiers in Pharmacology, 13, 909851.
    31. Salazar, J., A. Ghanem, R. H. Müller and J. P. Möschwitzer (2012). "Nanocrystals: comparison of the size reduction effectiveness of a novel combinative method with conventional top-down approaches." Eu-ropean Journal of Pharmaceutics and Biopharmaceutics 81(1): 82-90.
    32. Siepmann, J., and Siepmann, F. (2008). Mathematical modeling of drug delivery. International journal of pharmaceutics, 364(2), 328-343.
    33. Singh, S. K., K. K. Srinivasan, K. Gowthamarajan, D. S. Singare, D. Prakash and N. B. Gaikwad (2011). "Investigation of preparation parameters of nanosuspension by top-down media milling to improve the dissolution of poorly water-soluble glyburide." European Journal of Pharmaceutics and Biopharma-ceutics, 78(3): 441-446.
    34. Singh, S., Shyale, S. S., and Sandip, H. G. (2015). Improved dissolution properties of ketoconazole through application of liquisolid techniques. Int J Pharm Sci Nanotechnol, 8(4), 3053-3059.
    35. Souto, E. B., and Müller, R. H. (2005). SLN and NLC for topical delivery of ketoconazole. Journal of mi-croencapsulation, 22(5), 501-510.
    36. Touzet, A., Pfefferlé, F., Lamprecht, A. Pellequer Yann (2020). Formulation of Ketoconazole Nanocrys-tal-Based Cryopellets. AAPS PharmSciTech 21, 50. https://doi.org/10.1208/s12249-019-1570-1
    37. Wilson, G. (2004). Textbook of organic medical and pharmaceutical chemistry 11th ed, Lippincott William and Willcins Company, USA.
    38. Xi H., Laila J., Daniel T., Chinmay G., Rajesh D, (2013). Passivation of high-surface-energy sites of milled ibuprofen crystals via dry coating for reduced cohesion and improved flowability, Journal of Pharmaceu-tical Sciences, 102(7), 2282-2296. https://doi.org/10.1002/jps.23589.
    39. Yu, Q., Wu, X., Zhu, Q., Wu, W., Chen, Z., Li, Y., and Lu, Y. (2018). Enhanced transdermal delivery of meloxicam by nanocrystals: Preparation, in vitro and in vivo evaluation. Asian journal of pharmaceu-tical sciences, 13(6), 518-526.

    How to Cite

    Ketoconazole Nanocrystals Fortified Gel for Improved Transdermal Applications. (2024). Nanofabrication, 9. https://doi.org/10.37819/nanofab.9.1885
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    Ketoconazole Nanocrystals Fortified Gel for Improved Transdermal Applications. (2024). Nanofabrication, 9. https://doi.org/10.37819/nanofab.9.1885

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    Bhavin Vadher
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    Sunny Shah
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    Kiran Dudhat
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    Mori Dhaval
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    Sudarshan Sing
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    Bhupendra G Prajapati
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