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Transdermal Film Loaded with Avanafil Ultra-deformable Nanovesicles to Enhance its Percutaneous Absorption and Bioavailability

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Abstract

The in vitro dissolution of Avanafil (AVA) is the rate-limiting step for its bioavailability. Also, it undergoes the first-pass metabolism, and its absorption is altered significantly in the presence of food. So, our study aimed to overcome the previous hurdles and improve the AVA bioavailability by its incorporation in the ultra-deformable nanovesicles, transfersomes (TRF), then loading these nanovesicles in transdermal films. The AVA-loaded TRF formulation was optimized using Draper-Lin small composite design (D-LSCD). The optimized AVA-loaded TRF was evaluated for quality attributes and assessed for skin permeation using a fluorescence laser microscope and for pharmacokinetic parameters after topical application on the rats. The optimized AVA-loaded TRF showed a vesicle size of 97.75 nm, a zeta potential of −28.83 mV, and entrapment efficiency of 95.14% with good deformability and release profile. The intense discoloration in the deep skin layers of the rats indicated the permeation efficiency of AVA-loaded TRF films. The pharmacokinetic parameters specified the augmented absorption extent with Cmax of 254.66 ± 8.02 ng/mlversus 70.33 ± 3.05 ng/ml which reflected on the AUC0-inf that has a value of 2050.45 ± 159.14 ng/ml h versus 497.34 ± 102.61 ng/ml h for the optimized AVA-loaded TRF film and raw AVA-loaded film, respectively. These promising results wide open the field for broader clinical application of this alternative delivery pathway for superior bioavailability, efficacy, and patient compliance and satisfaction.

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Acknowledgements

The authors acknowledge with thanks to DSR for technical and financial support.

Funding

This research was funded by the Deanship of Scientific Research (DSR) at King Abdulaziz University, Jeddah, under grant no. (G:351-166-1441).

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Authors and Affiliations

  1. Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia

    Omar D. Al-hejaili, Abdullah A. Alamoudi, Osama A. A. Ahmed & Khalid M. El-Say

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  1. Omar D. Al-hejaili
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  2. Abdullah A. Alamoudi
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  4. Khalid M. El-Say
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Contributions

Conceptualization, A.A. and K.E.; methodology, O.D.A., A.A., and O.A.A.; software, K.E.; validation, A.A. and K.E.; formal analysis, K.E.; investigation, O.D.A., A.A., and O.A.A.; resources, O.D.A. and K.E.; data curation, O.D.A., A.A., O.A.A., and K.E.; writing—original draft preparation, O.D.A. and K.E.; writing—review and editing, O.D.A., A.A., O.A.A., and K.E.; visualization, O.D.A. and K.E.; supervision, A.A., O.A., and K.E.; project administration, K.E.; funding acquisition, K.E. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Khalid M. El-Say.

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Institutional Review Board Statement

The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Research Ethics Committee, Faculty of Pharmacy, King Abdulaziz University (Approval No. PH-119-41).

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The authors declare no competing interests.

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Al-hejaili, O.D., Alamoudi, A.A., Ahmed, O.A.A. et al. Transdermal Film Loaded with Avanafil Ultra-deformable Nanovesicles to Enhance its Percutaneous Absorption and Bioavailability. AAPS PharmSciTech 23, 46 (2022). https://doi.org/10.1208/s12249-021-02195-4

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