Tadalafil solid dispersion formulations based on PVP/VA S-630: Improving oral bioavailability in rats

    loading  Checking for direct PDF access through Ovid

Abstract

Here, solid dispersion (SD) techniques were utilized to improve the oral bioavailability of tadalafil (TDF). Poly(vinyl pyrrolidone-covinyl acetate) (PVP/VA S-630; 60% VP and 40% VA; MW 50,000) SD formulations were previously found to improve the solubility and dissolution (%) of TDF. The effect of various weak acids and bases on SD formulations was also investigated herein. PVP/VA S-630 SD formulations in combination with weak acids and bases increased the apparent solubility of TDF. After 1 h, the apparent solubility of PVP/VA S-630 SD formulations with MgO, meglumine, and tartaric acid were significantly higher by 387.0 ± 4.17, 376.8 ± 9.88, and 308.8 ± 4.17 μg/mL, respectively, than those of SD formulations without weak acids and bases (166.8 ± 0.50 μg/mL). The dissolution (%) of SD formulations with weak acids was under 60%; however, the dissolution (%) of those containing MgO, meglumine, and NaHCO3 was over 80% in distilled water (specifically 85.6%, 89.9%, and 91.6%, respectively). The optimal SD formulation contained meglumine (B-2); both its apparent solubility after 24 h and dissolution (%) were the highest among all SD formulations. The B-2 SD formulation showed no toxicity in Caco-2 cells after 24 h. The area under the concentration-time curve (AUClast) and peak plasma concentration (Cmax) of the orally administered B-2 SD formulation was greater than that with Cialis® powder in rats. We conclude that the B-2 SD formulation significantly improves the apparent solubility and dissolution (%) of TDF over that of commercially available products (i.e., Cialis®). Moreover, the B-2 SD formulation improves the relative bioavailability (BA) of TDF (21.9%) over that of Cialis®.

Related Topics

    loading  Loading Related Articles