Design, Development, and Evaluation of Constant Voltage Iontophoresis for the Transungual Delivery of Efinaconazole
The efficacy of topical antifungal therapy in onychomycosis has been hindered by the failure of the antimycotic to permeate the nail plate. This research aims to design and develop a transungual system for the effective delivery of efinaconazole utilizing constant voltage iontophoresis. Seven protot...
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MDPI AG
2023-05-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/5/1422 |
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| author | Anroop B. Nair Bandar Aldhubiab Jigar Shah Shery Jacob Mahesh Attimarad Nagaraja Sreeharsha Katharigatta N. Venugopala Alex Joseph Mohamed A. Morsy |
| author_facet | Anroop B. Nair Bandar Aldhubiab Jigar Shah Shery Jacob Mahesh Attimarad Nagaraja Sreeharsha Katharigatta N. Venugopala Alex Joseph Mohamed A. Morsy |
| author_sort | Anroop B. Nair |
| collection | DOAJ |
| description | The efficacy of topical antifungal therapy in onychomycosis has been hindered by the failure of the antimycotic to permeate the nail plate. This research aims to design and develop a transungual system for the effective delivery of efinaconazole utilizing constant voltage iontophoresis. Seven prototype drug-loaded hydrogel formulations (E1–E7) were prepared to assess the influence of solvent (ethanol) and cosolvent (Labrasol<sup>®</sup>) on transungual delivery. Optimization was performed to evaluate the effect of three independent variables; voltage, solvent-to-cosolvent ratio, and penetration enhancer (PEG 400) concentration on critical quality attributes (CQAs), such as drug permeation and loading into the nail. The selected hydrogel product was characterized for pharmaceutical properties, efinaconazole release from the nail, and antifungal activity. Preliminary data indicates ethanol, Labrasol<sup>®</sup>, and voltage influence the transungual delivery of efinaconazole. Optimization design indicates a significant impact by applied voltage (<i>p</i>-0.0001) and enhancer concentration (<i>p</i>-0.0004) on the CQAs. Excellent correlation between selected independent variables and CQAs was confirmed by the high desirability value (0.9427). A significant (<i>p</i> < 0.0001) enhancement in the permeation (~78.59 µg/cm<sup>2</sup>) and drug loading (3.24 µg/mg) was noticed in the optimized transungual delivery with 10.5 V. FTIR spectral data indicates no interaction between the drug and excipients, while the DSC thermograms confirmed the amorphous state of the drug in the formulation. Iontophoresis produces a drug depot in the nail that releases above the minimum inhibitory concentration level for an extended period, potentially reducing the need for frequent topical treatment. Antifungal studies further substantiate the release data and have shown remarkable inhibition of <i>Trichophyton mentagrophyte</i>. Overall, the promising results obtained here demonstrate the prospective of this non-invasive method for the effective transungual delivery of efinaconazole, which could improve the treatment of onychomycosis. |
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| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
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| publishDate | 2023-05-01 |
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| spelling | doaj.art-7c9c4ec2adff4bd8ba22727637bda7682023-11-18T02:51:21ZengMDPI AGPharmaceutics1999-49232023-05-01155142210.3390/pharmaceutics15051422Design, Development, and Evaluation of Constant Voltage Iontophoresis for the Transungual Delivery of EfinaconazoleAnroop B. Nair0Bandar Aldhubiab1Jigar Shah2Shery Jacob3Mahesh Attimarad4Nagaraja Sreeharsha5Katharigatta N. Venugopala6Alex Joseph7Mohamed A. Morsy8Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi ArabiaDepartment of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi ArabiaDepartment of Pharmaceutics, Institute of Pharmacy, Nirma University, Ahmedabad 382481, IndiaDepartment of Pharmaceutical Sciences, College of Pharmacy, Gulf Medical University, Ajman 4184, United Arab EmiratesDepartment of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi ArabiaDepartment of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi ArabiaDepartment of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi ArabiaDepartment of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, IndiaDepartment of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi ArabiaThe efficacy of topical antifungal therapy in onychomycosis has been hindered by the failure of the antimycotic to permeate the nail plate. This research aims to design and develop a transungual system for the effective delivery of efinaconazole utilizing constant voltage iontophoresis. Seven prototype drug-loaded hydrogel formulations (E1–E7) were prepared to assess the influence of solvent (ethanol) and cosolvent (Labrasol<sup>®</sup>) on transungual delivery. Optimization was performed to evaluate the effect of three independent variables; voltage, solvent-to-cosolvent ratio, and penetration enhancer (PEG 400) concentration on critical quality attributes (CQAs), such as drug permeation and loading into the nail. The selected hydrogel product was characterized for pharmaceutical properties, efinaconazole release from the nail, and antifungal activity. Preliminary data indicates ethanol, Labrasol<sup>®</sup>, and voltage influence the transungual delivery of efinaconazole. Optimization design indicates a significant impact by applied voltage (<i>p</i>-0.0001) and enhancer concentration (<i>p</i>-0.0004) on the CQAs. Excellent correlation between selected independent variables and CQAs was confirmed by the high desirability value (0.9427). A significant (<i>p</i> < 0.0001) enhancement in the permeation (~78.59 µg/cm<sup>2</sup>) and drug loading (3.24 µg/mg) was noticed in the optimized transungual delivery with 10.5 V. FTIR spectral data indicates no interaction between the drug and excipients, while the DSC thermograms confirmed the amorphous state of the drug in the formulation. Iontophoresis produces a drug depot in the nail that releases above the minimum inhibitory concentration level for an extended period, potentially reducing the need for frequent topical treatment. Antifungal studies further substantiate the release data and have shown remarkable inhibition of <i>Trichophyton mentagrophyte</i>. Overall, the promising results obtained here demonstrate the prospective of this non-invasive method for the effective transungual delivery of efinaconazole, which could improve the treatment of onychomycosis.https://www.mdpi.com/1999-4923/15/5/1422onychomycosisefinaconazoletransungualiontophoresisoptimizationantifungal |
| spellingShingle | Anroop B. Nair Bandar Aldhubiab Jigar Shah Shery Jacob Mahesh Attimarad Nagaraja Sreeharsha Katharigatta N. Venugopala Alex Joseph Mohamed A. Morsy Design, Development, and Evaluation of Constant Voltage Iontophoresis for the Transungual Delivery of Efinaconazole Pharmaceutics onychomycosis efinaconazole transungual iontophoresis optimization antifungal |
| title | Design, Development, and Evaluation of Constant Voltage Iontophoresis for the Transungual Delivery of Efinaconazole |
| title_full | Design, Development, and Evaluation of Constant Voltage Iontophoresis for the Transungual Delivery of Efinaconazole |
| title_fullStr | Design, Development, and Evaluation of Constant Voltage Iontophoresis for the Transungual Delivery of Efinaconazole |
| title_full_unstemmed | Design, Development, and Evaluation of Constant Voltage Iontophoresis for the Transungual Delivery of Efinaconazole |
| title_short | Design, Development, and Evaluation of Constant Voltage Iontophoresis for the Transungual Delivery of Efinaconazole |
| title_sort | design development and evaluation of constant voltage iontophoresis for the transungual delivery of efinaconazole |
| topic | onychomycosis efinaconazole transungual iontophoresis optimization antifungal |
| url | https://www.mdpi.com/1999-4923/15/5/1422 |
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