Study solubility and stability of amphotericin B in presence of biliary salts

Abstract

Introduction: Although amphotericin B is an antifungal agent with a broad spectrum of activity against many fungal species, low solubility severely hinders its clinical use. Different methods can be used to solve the issue mentioned above, among which bile acids have got our attention. Bile acids are receiving considerable interest by scientists in drug delivery research due to their peculiar physicochemical properties and biocompatibility. The main advantage of bile acids as drug absorption enhancers is their ability to ´increase the bioavailability of drugs whose absorption-limiting factors include either poor aqueous solubility or low membrane permeability. Aim: The aim of this work was to evaluate the potential of bile acids in increasing Amphotericin B´s solubility in water. Method: The shake flask method was used for solubility determination. Different concentrations of bile acids(0.4, 0.8, 1, 2) were added to a specific medium and shaked, and the saturation was confirmed by observation of the presence of on-dissolved material. After filtration of the slurry, a sample for analysis was taken and analyzed with a UV spectrometer. To evaluate the drug´s stability, amphotericin formulations that had a suitable solution were incubated at 40 ° C, and 75% humidity and stability studies were carried out, and the HPLC method was used. Results: Results showed that the solubility of amphotericin B in all formulations was higher than the pure drug. Among the formulations, A2 managed to increase the solubility and dissolution rate of amphotericin B more than the others. For potential interactions inspection, the best formulation was analyzed with ATR FTIR spectroscopy. The results showed that the drug had acceptable stability until the second month, but the stability has decreased sharply from the fourth month. Conclusion: Bile salts were able to increase drug solubility significantly; however, more studies are needed to provide better stability