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.

Abstract

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

Substances

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