Optimized sildenafil citrate fast orodissolvable film: a promising formula for overcoming the barriers hindering erectile dysfunction treatment

Abstract

Sildenafil citrate, a drug used to treat erectile dysfunction, is available in tablet form but has three major problems. First, the drug displays poor aqueous solubility, which delays its onset of action. Second, the drug undergoes extensive first-pass metabolism, resulting in a low (40%) bioavailability. Third, the gastrointestinal effects of sildenafil citrate include dyspepsia and a burning sensation. The objective of this study was to prepare sildenafil citrate using a fast orodissolvable film (ODF) containing the drug in a solid dispersion (SD) to mitigate the abovementioned problems. The solubility of sildenafil citrate in β-cyclodextrin derivatives was estimated, and SDs were prepared and characterized. To develop an ODF that disintegrates rapidly and releases the maximum amount of sildenafil citrate, a 3³ Box–Behnken experimental design was used to estimate the effects of different concentrations of film forming polymer (X₁), the film modifier (X₂), and the plasticizer (X₃) on the responses, i.e. the disintegration time (Y₁) and the amount of drug released (Y₂). Pharmacokinetic studies with the optimized (ODF) were conducted on human volunteers. SD prepared using hydroxybutyl-β-cyclodextrin enhanced the solubility of sildenafil citrate by more than eightfold. The Y₁ for the optimized ODF was 89 seconds, and the Y₂ was 86%; this formula also exhibited a rapid onset of action, and its bioavailability was enhanced by 2.25-fold compared with that of the marketed tablet. The ODF is a promising formulation for sildenafil citrate that results in higher solubility, a rapid onset of action, and enhanced systemic bioavailability.

• Box–Behnken design
• erectile dysfunction
• hydroxybutyl-β-cyclodextrin
• orodissolvable film
• sildenafil citrate

Declaration of interest

The authors state no conflicts of interest. This work was supported by the Deanship of Scientific Research (DSR) of King Abdulaziz University of Jeddah (Grant No. 166-005-D1433).

Acknowledgment

This work was funded by the The authors acknowledge and thank the DSR for the technical and financial support.