Formulation and Evaluation of Nanoemulgels for the Topical Drug Delivery of Posaconazole
Abstract
Objective: Posaconazole(POS) is an antifungal drug widely used in treatment of fungal infections. However, the drug has very low oral bioavailability due to high first-pass metabolism, thereby limiting its therapeutic effectiveness. The present study is aimed to prepare nanoemulsion of posaconazole to increase its solubility and to develop posaconazole-loaded nanoemulsion based gel for single dose topical administration to sustain the release of the drug, improve patient compliance and avoid repeated administration.
Method:-FTIR-study was performed to determine compatibility of drug with excipients. Pseudoternary-phase diagram was constructed to optimize the Smix ratio. Optimization of nanoemulsion was done by Box-Behnken Design. The optimized formulation was evaluated for particle-size (nm), polydispersity index (PDI), (%) drug content and in-vitro drug release. POS-nanoemulgel (FNG) was developed using carbopol-934P (1%), which was evaluated for homogeneity, pH, viscosity, spreadability, percentage-yield and in-vitro drug release. The anti-fungal activity of POS-nanoemulgel was evaluated against Candida Albicans.
Results: The FTIR-study confirmed that there was no interaction between drug and excipients. The optimized selected nanoemulsion (FN1) exhibited particle size 79.19nm, PDI 0.357, drug content 95.90% and in-vitro release of 79.40% at 24 hour. The prepared nanoemulgel was homogenous, opaque with good spreadability 13.91±1.19, viscosity 3760±0.014, pH 5.6±0.06 and the zeta-potential was -29mV, indicating good stability. The drug release at 24h was 72.01%. Further, the developed nanoemulgel formulation exhibited better antifungal activity in comparison to the pure drug gel.
Conclusion: Hence, it can be concluded that nanoemulgel of posaconazole can provide better antifungal activity and improve patient compliance.
Keywords: Nanoemulsion, Nanoemulgel, Posaconazole, Anti-fungal, Box-Behnken Design, Pseudoternary phase diagram.
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References
2. Berman J. Candida albicans. Current biology. 2012; 21;22(16):R620-2. https://doi.org/10.1016/j.cub.2012.05.043
3. Kuhbacher A, Henkel H, Stevens P, Grumaz C, Finkelmeier D, Burger-Kentischer A, Sohn K, Rupp S. Dermal fibroblasts play a central role in skin model protection against C. albicans invasion. J. Infect. Dis. 2017. https://doi.org/10.1093/infdis/jix153
4. Nayak D, Tawale RM, Aranjani JM, Tippavajhala VK. Formulation, optimization, and evaluation of novel ultra-deformable vesicular drug delivery system for an anti-fungal drug. American Association of Pharmaceutical Association, 2020; 21(5):1-0. https://doi.org/10.1208/s12249-020-01681-5
5. Chapman S. The radiological dating of injuries. Archives of disease in childhood. 1992; 67(9):1063. https://doi.org/10.1136/adc.67.9.1063
6. Ben-Ami R. Treatment of invasive candidiasis: A narrative review. Journal of Fungi. 2018; 16;4(3):97. https://doi.org/10.3390/jof4030097
7. Li Y, Theuretzbacher U, Clancy CJ, Nguyen MH, Derendorf H. Pharmacokinetic/pharmacodynamic profile of posaconazole. Clinical pharmacokinetics. 2010; 49(6):379-96. https://doi.org/10.2165/11319340-000000000-00000
8. Krishna G, Moton A, Ma L, Medlock MM, McLeod J. Pharmacokinetics, and absorption of posaconazole oral suspension under various gastric conditions in healthy volunteers. Antimicrobial agents and chemotherapy. 2009; 53(3):958-66. https://doi.org/10.1128/AAC.01034-08
9. Van der Elst KC, Brouwers CH, van den Heuvel ER, van Wanrooy MJ, Uges DR, van der Werf TS, Kosterink JG, Span LF, Alffenaar JW. Subtherapeutic posaconazole exposure and treatment outcome in patients with invasive fungal disease. Therapeutic Drug Monitoring. 2015; 37(6):766-71. https://doi.org/10.1097/FTD.0000000000000235
10. Alghamdi S, Asif M. The Posaconazole and Its Pharmacologic and clinical Uses: An Antifungal Drugs: Potentials of Posaconazole. Journal of Biological Studies. 2022; 30;5(2):285-319.
11. Jain AK, Jain S, Abourehab MA, Mehta P, Kesharwani P. An insight on topically applied formulations for management of various skin disorders. Journal of Biomaterials Science, Polymer Edition. 2022; 19:1-27.)
12. Sharadha M, Gowda DV, Gupta V, Akhila AR. An overview on topical drug delivery system-updated review. International Journ al of Research in Pharmaceutical Sciences. 2020; 11(1):368-85. https://doi.org/10.26452/ijrps.v11i1.1831
13. Singhvi G, Patil S, Girdhar V, Dubey SK. Nanocarriers for topical drug delivery: approaches and advancements. Nanoscience & Nanotechnology-Asia. 2019; 9(3):329-36. https://doi.org/10.2174/2210681208666180320122534
14. Chavda VP. Nanotherapeutics and nanobiotechnology. In Applications of Targeted Nano Drugs and Delivery Systems 2019; 1:1-13. https://doi.org/10.1016/B978-0-12-814029-1.00001-6
15. Zhang Z, McClements DJ. Overview of nanoemulsion properties: stability, rheology, and appearance. In Nanoemulsions 2018; (pp. 21-49). https://doi.org/10.1016/B978-0-12-811838-2.00002-3
16. Chellapa P, Mohamed AT, Keleb EI, Elmahgoubi A, Eid AM, Issa YS, Elmarzugi NA. Nanoemulsion and nanoemulgel as a topical formulation. International Organization of Scientific Research 2015; 5(10):43-7.
17. Ahmad J, Gautam A, Komath S, Bano M, Garg A, Jain K. Topical nano-emulgel for skin disorders: Formulation approach and characterization. Recent patents on anti-infective drug discovery. 2019; 14(1):36-48. https://doi.org/10.2174/1574891X14666181129115213
18. Dev A, Chodankar R, Shelke O. Emulgels: a novel topical drug delivery system. Pharmaceutical and biological evaluations. 2015; 26; 2(4):64-75.
19. Arora R, Khan R, Ojha A, Upadhyaya K, Chopra H. Emulgel: A novel approach for hydrophobic drugs. International Journal of Pharmacy and Biological Sciences. 201; 7(3):43-60.
20. Gurpreet K, Singh SK. Review of nanoemulsion formulation and characterization techniques. Indian Journal of Pharmaceutical Sciences. 2018; 80(5):781-9. https://doi.org/10.4172/pharmaceutical-sciences.1000422
21. Ahmad J, Amin S, Kohli K, Mir SR. Construction of pseudoternary phase diagram and its evaluation: development of self-dispersible oral formulation. International Journal of Drug Development and Research. 2013; 5(2):0-.
22. Wang Z. Pseudo-ternary phase diagrams of a drug delivery system (Master's thesis, University of Waterloo).
23. Aslan NE, Cebeci YA. Application of Box-Behnken design and response surface methodology for modeling of some Turkish coals. Fuel. 2007; 86(1-2):90-7. https://doi.org/10.1016/j.fuel.2006.06.010
24. Dong CH, Xie XQ, Wang XL, Zhan Y, Yao YJ. Application of Box-Behnken design in optimisation for polysaccharides extraction from cultured mycelium of Cordyceps sinensis. Food and bioproducts processing. 2009; 87(2):139-44. https://doi.org/10.1016/j.fbp.2008.06.004
25. Aslan NE, Cebeci YA. Application of Box-Behnken design and response surface methodology for modeling of some Turkish coals. Fuel. 2007; 86(1-2):90-7. https://doi.org/10.1016/j.fuel.2006.06.010
26. Brahmankar DM, Jaiswal SB. Biopharmaceutics and pharmacokinetics: A treatise. Vallabh prakashan; 2005.
27. Aljaeid BM, Hosny KM. Miconazole-loaded solid lipid nanoparticles: formulation and evaluation of a novel formula with high bioavailability and antifungal activity. International Journal of Nanomedicine. 2016; 11:441.78. https://doi.org/10.2147/IJN.S100625
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