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Although the use of phosphodiesterase 5 inhibitors (<jats:styled-content style=\"fixed-case\">PDE<\/jats:styled-content>5is) has revolutionized the treatment of <jats:styled-content style=\"fixed-case\">ED<\/jats:styled-content>, a high percentage of <jats:styled-content style=\"fixed-case\">ED<\/jats:styled-content> patients discontinue <jats:styled-content style=\"fixed-case\">PDE<\/jats:styled-content>5i treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>(i) To analyze the reasons for patient dissatisfaction leading to <jats:styled-content style=\"fixed-case\">PDE<\/jats:styled-content>5i discontinuation; (ii) analyze the pharmacokinetics of new formulations focusing on the time needed to reach an effective plasma concentration of <jats:styled-content style=\"fixed-case\">PDE<\/jats:styled-content>5is (T<jats:sub>onset<\/jats:sub>) following drug intake; and (iii) summarize the physicochemical properties of sildenafil to understand which excipients may increase the absorption rate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and methods<\/jats:title><jats:p>An online PubMed literature search was conducted to identify English language publications from inception to January 2019.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The main reasons for patient dissatisfaction when using <jats:styled-content style=\"fixed-case\">PDE<\/jats:styled-content>5is on demand are the relatively long T<jats:sub>onset<\/jats:sub> after taking vardenafil and sildenafil, including formulations such as film\u2010coated tablets, fine granules, orally disintegrating tablets (<jats:styled-content style=\"fixed-case\">ODT<\/jats:styled-content>s), and oral thin films (<jats:styled-content style=\"fixed-case\">ODF<\/jats:styled-content>s). The relatively long T<jats:sub>onset<\/jats:sub>, further worsened when accompanied by eating, highlights the following: (i) the need for planning intercourse, determining partner\u2010related issues; (ii) issues when having sex before the maximum effect of the drug; and (iii) lower drug\u2010related placebo effects. Some data suggest that sildenafil is a \u2018difficult\u2019 molecule, but T<jats:sub>onset<\/jats:sub> can be improved following absorption by buccal mucosa using appropriate excipients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We conclude that several <jats:styled-content style=\"fixed-case\">ODT<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">ODF<\/jats:styled-content> formulations can improve the \u2018discretion\u2019 issue because they are taken without water, but they have similar pharmacokinetics to corresponding film\u2010coated tablet formulations. One <jats:styled-content style=\"fixed-case\">ODF<\/jats:styled-content> formulation of sildenafil was characterized by a shorter T<jats:sub>onset<\/jats:sub> and could potentially increase patient satisfaction following treatment. However, more clinical studies are needed to confirm the findings. 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