Azithromycin water solubility improvement with glutamic acid

Rosario

Congreso; 7ma Reunión Internacional de Ciencias Farmacéuticas; 2023

Universidad Nacional de Rosario

Microorganisms can develop antimicrobial resistance (AMR) when they mutate, losing their susceptibility to the effects of antimicrobial drugs. The World Health Organization lists this issue as one of the top 10 public health hazards, and it continues to escalate because fewer new antimicrobials are being developed. This is due to the time and money needed to conduct extensive research on innovative medications.1 In this context, using already-approved medications with improved physicochemical qualities is a common strategy for creating new formulations. Among them, the use of amino acids as co-formers has been reported to have enhanced the solubility of drugs. 2The present work aims to increase the aqueous solubility of azithromycin (AZT) through the formation of binary systems with the addition of glutamic acid (GLU). For this purpose, the solid system of AZT:GLU was obtained by the drop-assisted grinding method in a 1:1 stoichiometry ratio. The solubility and dissolution behavior of the solids were assayed. The antimicrobial effect of AZT and AZT:GLU against Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922 were determined by the agar disc diffusion method, according to the Clinical Laboratory Standards Institute. All AZT concentration measurements were determined through high performance liquid chromatography (HPLC). Solid characterization was carried out through Fourier transform-infrared spectroscopy (FTIR), hot stage microscopy (HSM), X-ray diffraction (PRDX), and contact angle measurements.The saturation assay yielded higher solubility values of AZT in the binary system (2.73 mg/mL) compared to AZT pure (0.09 mg/mL). Microbiological tests corroborated that the AZT:GLU system does not modify the antimicrobial activity of AZT against either of the two species tested. About solid characterization, FTIR, HSM, and PRDX results show differences between AZT:GLU and pure components, evidencing the interaction between AZT and GLU. The values of the contact angle for AZT and AZT:GLU were 106 ± 3° and 80 ± 1°, respectively. These results correlate with the observed fast higher percentages of AZT dissolved from AZT:GLU compared with raw AZT.In conclusion, through all the analyses carried out in this study, it was demonstrated that the binary systems of AZT and GLU obtained represent an adequate strategy for increasing the aqueous solubility and improving the dissolution profile of the drug. 1- Organización Mundial de la Salud. Resistencia a los antimicrobianos. https://www.who.int/es/news-room/fact-sheets/detail/antimicrobial-resistance2- Idrees, M., Mohammad, A. R., Karodia, N., & Rahman, A. Multimodal Role of Amino Acids in Microbial Control and Drug Development. Antibiotics, 9(6), 330. https://doi.org/10.3390/antibiotics9060330