Clarithromycin:Ascorbic Acid binary system, development and evaluation

Rosario

Congreso; 7ma Reunión Internacional de Ciencias Farmacéuticas; 2023

Universidad Nacional de Rosario

Abstract: Clarithromycin (CLM) is a semi-synthetic macrolide with a broad spectrum of antimicrobial activity. In order to improve the antimicrobial and antibiofilm activity of this drug, a new binary system (BS) of CLM and ascorbic acid (AA) was prepared in a solid state and evaluated. Recently, we demonstrated that the interaction of CLM and AA increases the solubility of CLM 60-fold 1, which could optimize its microbiological activity.The objective of this work was to prepare and characterize the BS in solid state, and evaluate its antimicrobial and antibiofilm activity against a clinical Staphylococcus aureus.The CLM:AA BS (1:2 molar ratio) was prepared in a solid state by physical mixture (PM) and kneaded (K) in an agate mortar. It was characterized by infrared spectroscopy (FTIR), hot-stage microscopy (HSM), thermogravimetric analysis (TGA), and X-ray diffraction (PRDX). The antimicrobial effect of CLM and BS against clinical S. aureus was determined by the agar disc diffusion method, according to the Clinical Laboratory Standards Institute (CLSI). The minimum inhibitory concentration (MIC) of CLM was determined by the dilution method according to CLSI guidelines. Furthermore, antibiofilm activity was determined by the MTT method using CLM concentrations equivalent to 100 x MIC [50 μg/ml].The characterization of this system by FTIR showed the appearance of a new band at 1589 cm-1, which can be attributed to the formation of the ascorbate anion, which could indicate the formation of a salt with clarithromycin. The results obtained by HSM and TGA exhibited different thermal behaviour, while in PRDX, different diffraction patterns could be observed between BS and pure drugs. According to the antibacterial activity, the results showed that the CLM:AA binary complex presented a significantly higher inhibition zone (31,0 + 0,03 mm) than pure CLM (25 + 1 mm). This could be related to the fact that the combination of CLM and AA results in a synergistic effect of both drugs when combined. Finally, it was observed that both CLM and the solid BS showed decreased biofilm viability. Likewise, the BS showed a significant reduction in cell viability compared to pure CLM.In conclusion, a BS CLM:AA (1:2) was prepared using a simple method. This BS showed higher antibacterial and antibiofilm activity than pure CLM. Therefore, this system is promising because of its interesting antimicrobial potential, which may translate into a better therapeutic effect of CLM.1 A. Bartolilla, A. Zoppi, M.R. Longhi, V. Aiassa. Binary systems of clarithromycin: An alternative to enhancement its solubility and antimicrobial activity. 6ta Reunión Internacional de Ciencias Farmacéuticas (RICiFa 2021), Córdoba, Argentina, 10 al 12 de noviembre de 2021.Acknowledgements: Casasco Laboratories for kindly donating clarithromycin.