Comparative studies on amphotericin B nanosuspensions prepared by a high pressure homogenization method and an antisolvent precipitation method

[Display omitted] •AmB-HPH and AmB-AP improved the solubility and bioavailability of amphotericin B.•The solubility and dissolution of AmB-AP were superior to those of AmB-HPH.•AmB-HPH exhibited higher relative bioavailability than AmB-AP. Amphotericin B (AmB) is a widely used polyene antifungal agent; however, its poor solubility limits its clinical application. In this study, AmB nanosuspensions were prepared by a high pressure homogenization method (AmB-HPH) and an antisolvent precipitation method (AmB-AP) to improve the drug solubility. To reveal the distinct influences of these two different preparation methods, systematic comparisons of particle size, crystalline state, wettability, in vitro dissolution and in vivo pharmacokinetics on the properties of AmB-HPH and AmB-AP were performed. The results indicated that AmB-AP was in an amorphous state, exhibiting higher saturation solubility and dissolution rate than those of AmB-HPH in the crystalline state. However, the relative bioavailability of AmB-HPH was higher than that of AmB-AP in vivo, which was likely attributed to its better stability. In conclusion, both AmB-HPH and AmB-AP can enhance the solubility and bioavailability of AmB, but the stability of the nanosuspension prepared by the anti-solvent precipitation method should be carefully considered.