Enhanced Dissolution of Amphotericin B through Development of Amorphous Solid Dispersions Containing Polymer and Surfactants

Abstract

Amphotericin B (AmB) is the gold standard for antifungal therapy; however, its poor solubility limits its administration via intravenous infusion. A promising formulation strategy to achieve an oral formulation is the development of amorphous solid dispersions (ASDs) via spray-drying. Inclusion of surfactants into ASDs is a newer concept, yet it offers increased dissolution opportunities when combined with a polymer (HPMCAS 912). We developed both binary ASDs (AmB:HPMCAS 912 or AmB:surfactant) and ternary ASDs (AmB:HPMCAS 912:surfactant) using a variety of surfactants to determine the optimal surfactant carbon chain length and functional group for achieving maximal AmB concentration during in vitro dissolution. The ternary ASDs containing surfactants with a carbon chain length of 14 ± 2 carbons and a sulfate functional group increased the dissolution of AmB by 90-fold compared to crystalline AmB. These same surfactants, when added to a binary ASD, however, were only able to achieve up to a 40-fold increase, alluding to a potential interaction occurring between excipients or excipient and drug. This potential interaction was supported by dynamic light scattering data, in which the ternary formulation produced a single peak at 895.2 dnm. The absence of more than one peak insinuates that all three components are interacting in some way to form a single structure, which may be preventing AmB self-aggregation, thus improving the dissolution concentration of AmB.