Drug design, development and therapy · 2025
From Oral to Sublingual: A Redefined Avanafil Tablet with a Breakthrough in Bioavailability and First-Pass Metabolism Avoidance.
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Asar Turky Omar, Al-Hejaili Omar D, El-Sawy Hossam S, Abd-Allah Fathy I, Omar Abdelsattar M, Ahmed Tarek A, El-Say Khalid M
Аннотация
INTRODUCTION: Avanafil (AVA) is a very efficient phosphodiesterase type 5 inhibitor for the treatment of erectile dysfunction. However, it has limited bioavailability when taken orally and considerable first-pass metabolism. Enhancing its solubility and choosing an alternative delivery route may enhance its effectiveness and duration of action.
METHODS: Eight complex formulations were elaborated and analyzed at various ratios using different polyethylene glycols and hydroxypropyl-beta-cyclodextrin (HP-β-CD). Sublingual tablets containing AVA were designed and optimized using the Quality-by-design approach. The tablets' pre-compression and post-compression properties were evaluated. The in-vivo pharmacokinetic behavior of the optimized tablet was assessed and compared with that of the commercial oral tablets in human volunteers.
RESULTS: The HP-β-CD-AVA inclusion complex (1:1 molar ratio) showed an optimum solubilization capacity with an amount suitable for incorporation into sublingual tablets. The total amounts of superdisintegrants and Plasdone XL and the percentage of starch significantly influenced the length of time it took for 80% of the AVA to be released from the sublingual tablets, the tablet hardness, and the length of time for tablet disintegration. The optimized AVA sublingual tablet exhibited a 5.98-fold increase in the AVA mean residence time over the commercial tablet, with greater plasma exposure over 72 hours and 1356.42% relative bioavailability.
CONCLUSION: The sublingual tablets of the solubility-enhanced HP-β-CD-AVA inclusion complex represent a promising strategy to improve AVA bioavailability and bypass the first-pass effect. Furthermore, their extended activity offers potential clinical benefits, particularly for ED patients, such as ease of administration and reduced side effects.
METHODS: Eight complex formulations were elaborated and analyzed at various ratios using different polyethylene glycols and hydroxypropyl-beta-cyclodextrin (HP-β-CD). Sublingual tablets containing AVA were designed and optimized using the Quality-by-design approach. The tablets' pre-compression and post-compression properties were evaluated. The in-vivo pharmacokinetic behavior of the optimized tablet was assessed and compared with that of the commercial oral tablets in human volunteers.
RESULTS: The HP-β-CD-AVA inclusion complex (1:1 molar ratio) showed an optimum solubilization capacity with an amount suitable for incorporation into sublingual tablets. The total amounts of superdisintegrants and Plasdone XL and the percentage of starch significantly influenced the length of time it took for 80% of the AVA to be released from the sublingual tablets, the tablet hardness, and the length of time for tablet disintegration. The optimized AVA sublingual tablet exhibited a 5.98-fold increase in the AVA mean residence time over the commercial tablet, with greater plasma exposure over 72 hours and 1356.42% relative bioavailability.
CONCLUSION: The sublingual tablets of the solubility-enhanced HP-β-CD-AVA inclusion complex represent a promising strategy to improve AVA bioavailability and bypass the first-pass effect. Furthermore, their extended activity offers potential clinical benefits, particularly for ED patients, such as ease of administration and reduced side effects.