Study of amphotericin B solubility with different concentrations of cyclodextrin

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 cyclodextrins have got our attention . Cyclodextrins are macrocyclic oligosaccharides that consist of a hydrophilic outer part and a hydrophobic inner cavity. The hydrophobic part of the low solubility drug is placed in its cavity and the inclusion complex is formed. The main advantage of cyclodextrins as drug solubility enhancers is their ability to increase or maintain the stability of drugs that are sensitive to environmental factors. Aim: The aim of this work was to evaluate the potential of cyclodextrins in increasing Amphotericin B´s solubility in water. Method: The phase solubility method developed by Higuchi and Connors method was used for solubility determination .Different concentrations of cyclodextrins were added to a specific medium and shaked, and the saturation was confirmed by observation of the presence of undissolved 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, H1 managed to increase the solubility and dissolution rate of amphotericin B more than the others and had an acceptable amount of excipient. For potential interactions inspection . The results showed that the drug had acceptable stability and maybe increase stability of drug-CD complex. accelerated stability test was accebtable result. Conclusion: Cyclodextrins were able to increase drug solubility and stability significantly.