Formulações sólidas autoemulsionantes contendo anfotericina B: um estudo de pré-formulação

Introduction: Amphotericin B (AmB) is a macrolide derived from Streptomyces nodosus used to treat fungal infections and leishmaniasis. Its main clinical limitation is associated with severe nephrotoxicity after iv administration. Aim: Therefore, this study aimed to develop and characterize AmB-loaded solid self-emulsifying drug delivery systems (SEDDS) for oral administration. Methodology: to reach this goal, first an extensive solubility test was performed on 45 excipients, followed by a pseudo-ternary phase diagram to understand the phase behavior after mixing the chosen excipients with intestinal biorelevant media. Thereafter, solid SEDDS were produced either by filling hard capsules with SEDDS (LFC) or by adsorbing them onto solid excipients to formulate tablets and granules. Results: Phosal 50 PG presented the highest AmB solubility, and based on the phase behavior, two formulations with different oil-surfactant proportions were selected. The nitrogen adsorption method indicated that solid excipients incorporated the SEDDS, and no significant difference between these two formulations was found regarding droplet size, PDI, and AmB concentration. Conclusions: the LFC revealed to be the most promising dosage form, not only carrying the highest drug load, but also displaying an average size assigned as the ideal range for intestinal absorption. Therefore, supporting further in vivo studies to evaluate its therapeutic potential.