Rapid-Onset Sildenafil Sublingual Drug Delivery Systems: In Vitro Evaluation and In Vivo Pharmacokinetic Studies in Rabbits

J Pharm Sci. 2016 Sep;105(9):2774-2781. doi: 10.1016/j.xphs.2016.01.015. Epub 2016 Mar 15.


The aim of the present study was to prepare sublingual delivery systems for sildenafil and evaluate its relative bioavailability after sublingual administration in rabbits to attain a rapid onset of action with good efficacy at lower doses. For sublingual application, sildenafil and its citrate were formulated in 2 different dosage forms: the first was a sublingual spray consisting of sildenafil in 2 microemulsion systems, oleic acid or propylene glycol (PG), and the second was sublingual tablets prepared with various granulated sublingual sprays adsorbed onto a silicate adsorbant (Florite(®) R), binders (Cyclocel(®) or EMDEX(®)), and disintegrants (Ac-Di-Sol(®) or Kollidon(®) CL). Results showed that sublingual absorption of sildenafil spray prepared with PG was fairly rapid. At a 0.5-mg dose, the mean onset of action was 1.3 ± 0.6 min and lasted for about 1.5 h according to the pharmacokinetic studies. In vivo studies also showed that for sublingual tablets formulated with sildenafil in PG adsorbed onto Florite(®) R at a 1:1 weight ratio then mixed with Cycloel(®) and Ac-Di-Sol(®), the onset action was fast at 1.9 ± 0.4 min and lasted for about 1 h at 0.5 mg. These findings suggest the potential for the sublingual delivery of sildenafil instead of the conventional oral administration.

Keywords: bioavailability; erectile dysfunction; sildenafil; sublingual spray; sublingual tablets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Sublingual
  • Animals
  • Biological Availability
  • Drug Compounding
  • Drug Delivery Systems
  • Excipients
  • Hardness
  • Male
  • Oleic Acid
  • Pharmaceutical Vehicles
  • Propylene Glycol
  • Rabbits
  • Sildenafil Citrate / administration & dosage*
  • Sildenafil Citrate / pharmacokinetics
  • Solubility
  • Tablets
  • Vasodilator Agents / administration & dosage*
  • Vasodilator Agents / pharmacokinetics


  • Excipients
  • Pharmaceutical Vehicles
  • Tablets
  • Vasodilator Agents
  • Oleic Acid
  • Propylene Glycol
  • Sildenafil Citrate