ADVANCING TOPICAL POSACONAZOLE DELIVERY: BOX BEHNKEN DESIGN MICROSPONGE HYDROGEL OPTIMIZATION AND EXTENSIVE IN VIVO INVESTIGATION

REKHA RANI KUPPALA; P. RAVI PRAKASH; N. DEVANNA

doi:10.22159/ijap.2024v16i6.51167

Authors

REKHA RANI KUPPALA Research and Development, Department of Pharmaceutical Sciences, Jawaharlal Nehru Technological University, Anantapur-515001, AP, India https://orcid.org/0000-0001-5329-6878
P. RAVI PRAKASH Department of Pharmaceutics, Creative Educational Society’s College of Pharmaceutical Sciences (Affiliated to Jawaharlal Nehru Technological University, Anantapur), Kurnool, AP, India
N. DEVANNA Department of Chemistry, Jawaharlal Nehru Technological University, Anantapur-515001, AP, India

DOI:

https://doi.org/10.22159/ijap.2024v16i6.51167

Keywords:

Drug permeation, Microsponge hydrogel, Posaconazole, Skin fungal infections, Topical

Abstract

Objective: The primary aim of this study was to develop a novel hydrogel formulation containing Posaconazole (PCZ) encapsulated within microsponges. Furthermore, the study aimed to assess the permeation properties of this formulation in vivo using a mouse model.

Methods: To achieve this aim, a series of seventeen trials were conducted using the Box Behnken Design methodology. These trials were designed to optimize the production of PCZ Microsponges (PCZ MS), which were subsequently incorporated into a hydrogel matrix. Skin permeation studies were then performed to evaluate the ability of the PCZ microsponge-based hydrogel to deliver the drug across the skin barrier. These studies involved comparison with a standard hydrogel formulation lacking microsponges.

Results: This study assessed the efficacy of microsponge gel formulation PM-3 for drug entrapment, yield, and sustained release compared to a conventional gel. PM-3 displayed the highest entrapment efficiency of 98.5% and a yield of 95.62%, indicating a direct correlation with the 1:1 drug-polymer ratio. Moreover, PM-3 exhibited sustained drug release over 12 h, releasing 83.82% of PCZ compared to 65.31% with the normal gel, suggesting its potential for prolonged therapeutic action. These findings underscore the promise of microsponge-based hydrogels, like PM-3, in enhancing therapeutic outcomes through sustained drug release, warranting further exploration for clinical applications.

Conclusion: The findings of this study highlight the promising potential of microsponge-based hydrogels as effective carriers for localized drug delivery, particularly in the context of treating skin fungal infections.

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References

Durgun ME, Kahraman E, Hacıoglu M, Gungor S, Ozsoy Y. Posaconazole micelles for ocular delivery: in vitro permeation ocular irritation and antifungal activity studies. Drug Deliv Transl Res. 2022;12(3):662-75. doi: 10.1007/s13346-021-00974-x, PMID 33830458.

Priyadarshini P, Karwa P, Syed A, Asha AN. Formulation and evaluation of nanoemulgels for the topical drug delivery of posaconazole. J Drug Delivery Ther. 2023;13(1):33-43. doi: 10.22270/jddt.v13i1.5896.

Ghurghure SM, Jadhav T, Kale S, Phatak AA. Formulation and evaluation of posaconazole-loaded nanostructured lipid carriers for topical drug delivery system. CTPPC. 2022;4(3):126-34. doi: 10.18231/j.ctppc.2022.022.

Gupta AK, Talukder M, Venkataraman M. Review of the alternative therapies for onychomycosis and superficial fungal infections: posaconazole, fosravuconazole voriconazole oteseconazole. Int J Dermatol. 2022;61(12):1431-41. doi: 10.1111/ijd.15999, PMID 34882787.

Subair TK, Mohanan J. Development of nano-based film-forming gel for prolonged dermal delivery of luliconazole. Int J Pharm Pharm Sci. 2022;14(2):31-41. doi: 10.22159/ijpps.2022v14i2.43253.

Prakash PR, Rao NR, Chowdary S. Formulation evaluation and anti-inflammatory activity of topical etoricoxib gel. Asian J Pharm Clin Res. 2010;3(2):126-9.

Mohammed BS, Al Gawhari FJ. Preparation of posaconazole nanosponges for improved topical delivery system. Int J Drug Deliv Technol. 2022;12(1):8-14. doi: 10.25258/ijddt.12.1.2.

Baig RP, wais M. Formulation and development of proniosomal gel for topical delivery of amphotericin B. Int J Pharm Sci. 2022;14(1):37-49. doi: 10.22159/ijpps.2022v14i1.43237.

Ambikar RB, Bhosale AV. Development and characterization of diclofenac sodium loaded eudragit RS100 polymeric microsponge incorporated into in situ gel for ophthalmic drug delivery system. Int J Pharm Pharm Sci. 2021;13(9):63-9. doi: 10.22159/ijpps.2021v13i9.42405.

Singhvi G, Manchanda P, Hans N, Dubey SK, Gupta G. Microsponge: an emerging drug delivery strategy. Drug Dev Res. 2019;80(2):200-8. doi: 10.1002/ddr.21492, PMID 30456763.

Abdul AH, Bala AG, Chintaginjala H, Manchikanti SP, Kamsali AK, Dasari RR. Equator assessment of nanoparticles using the design expert software. Int J Pharm Sci Nanotechnol. 2020;13(1):4766-72. doi: 10.37285/ijpsn.2020.13.1.5.

Yadiki MN, Suggala VS, Puchalapalli DS, Ahad HA. Temperature and exposure time impact on the extraction of opuntia ficus indica and opuntia dillenii cladodes on % yield as a response: screening using design expert software. GJMPBU. 2022;17:17. doi: 10.25259/GJMPBU_55_2022.

Dwivedi G, Sharma MP. Application of box-Behnken design in optimization of biodiesel yield from pongamia oil and its stability analysis. Fuel. 2015;145:256-62. doi: 10.1016/j.fuel.2014.12.063.

Annepogu H, Ahad HA, Nayakanti D. Determining the best poloxamer carrier for thiocolchicoside solid dispersions. Turk J Pharm Sci. 2020;17(4):372-80. doi: 10.4274/tjps.galenos.2019.78800, PMID 32939132.

Lakshmi P, Kumar MK, Sridharan A, Bhaskaran S. Formulation and evaluation of ibuprofen topical gel: a novel approach for penetration enhancement. Int J Appl Pharm. 2011;3(3):25-30.

Ahad HA, Haranath C, Rahul Raghav D, Gowthami M, Naga Jyothi V, Sravanthi P. Overview on recent optimization techniques in gastro retentive microcapsules by factorial design. Int J Pharm Sci Res. 2019;10(9):247-54. doi: 10.13040/IJPSR.0975-8232.10(9).247-54.

Kumar A, Prasad JK, Editors. An recent advancement in topical dosage forms: a review. IJCP. 2021;13(2):58-9. doi: 10.29005/IJCP.2021.13.2.58-59.

Pawar AP, Gholap AP, Kuchekar AB, Bothiraja C, Mali AJ. Formulation and evaluation of optimized oxybenzone microsponge gel for topical delivery. J Drug Deliv. 2015;2015:261068. doi: 10.1155/2015/261068, PMID 25789176.

Kasar PM, Kale KS, Phadtare DG. Formulation and evaluation of topical antifungal gel containing itraconazole. Res J Top Cosmet Sci. 2018;9(2):49-52. doi: 10.5958/2321-5844.2018.00010.9.

Bothiraja C, Gholap AD, Shaikh KS, Pawar AP. Investigation of ethyl cellulose microsponge gel for topical delivery of eberconazole nitrate for fungal therapy. Ther Deliv. 2014;5(7):781-94. doi: 10.4155/tde.14.43, PMID 25287385.

Mahesh Kumar PM, Ghosh A. Development and evaluation of metronidazole loaded microsponge based gel for superficial surgical wound infections. J Drug Deliv Sci Technol. 2015;30:15-29. doi: 10.1016/j.jddst.2015.09.006.

Nagula RL, Wairkar S. Cellulose microsponges based gel of naringenin for atopic dermatitis: design optimization in vitro and in vivo investigation. Int J Biol Macromol. 2020;164:717-25. doi: 10.1016/j.ijbiomac.2020.07.168, PMID 32698069.

V. Kadam V, Patel V, S Karpe M, J Kadam V. Design development and evaluation of celecoxib loaded microsponge-based topical gel formulation. ACCTRA. 2016;3(1):44-55. doi: 10.2174/2213476X03666160308000647.

Bansode AS, Kute VB, Vethekar KS, Kote PS, Varhadi MK, Bansode AS. Formulation development and evaluation of microsponge-loaded topical gel of nystatin. J Drug Deliv Ther. 2019;9(2-S)451-61. doi: 10.22270/jddt.v9i2-s.2699.

Mohanty D, Bakshi V, Rashaid MA, Reddy TV, Dholakia NA, Babu AM. Design and in vitro characterization of betamethasone microsponge-loaded topical gel. Int J Pharm Res Health Sci. 2016;4(2):1124-9.

Khattab A, Nattouf A. Optimization of entrapment efficiency and release of clindamycin in microsponge-based gel. Sci Rep. 2021;11(1):23345. doi: 10.1038/s41598-021-02826-7, PMID 34857863.

Patel SS, Patel MR, Patel MJ. Formulation and evaluation of microsponge-based nicorandil sustained released tablet. J Sci Res. 2017;9(3):285-96. doi: 10.3329/jsr.v9i3.31193.

Tripathi PK, Gorain B, Choudhury H, Srivastava A, Kesharwani P. Dendrimer entrapped microsponge gel of dithranol for effective topical treatment. Heliyon Heliyon. 2019;5(3):e01343. doi: 10.1016/j.heliyon.2019.e01343, PMID 30957038.

Ivanova NA, Trapani A, Franco CD, Mandracchia D, Trapani G, Franchini C. In vitro and ex vivo studies on diltiazem hydrochloride loaded microsponges in rectal gels for chronic anal fissures treatment. Int J Pharm. 2019;557:53-65. doi: 10.1016/j.ijpharm.2018.12.039, PMID 30580086.

Kumar PM, Ghosh A. Development and evaluation of silver sulfadiazine loaded microsponge based gel for partial thickness (second degree) burn wounds. Eur J Pharm Sci. 2017;96:243-54. doi: 10.1016/j.ejps.2016.09.038, PMID 27697504.