Clarithromycin:N-acetylcysteine co-amorphous combination as alternative to improve solubility and antibiofilm activity.

CAMPO MANUELA ; AIASSA VIRGINIA; GUALDESI MARÍA S; ZOPPI ARIANA; LONGHI MARCELA R

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencia 2019; 2019

SAIC-SAFE-SAB-SAP

Clarithromycin (CLM) is a semisynthetic 14-member macrolide exhibiting a broad in vitro antibacterial spectrum and a variety of clinically diagnosed infections. It is a water-insoluble base (pKa = 8.76) and with pH-dependent solubility. One approach that has been explored to overcome the problem of poor aqueous solubility is by using a pharmacologically relevant combination of two drugs in the preparation of co-amorphous systems. In this work, CLM:N-acetylcysteine (NAC) system was prepared with the aim of improving the solubility and antibiofilm activity of CLM. The NAC, with a carboxylic functional group, was selected as salifying agent due to its well-known mucolytic activity.The CLM:NAC solid systems were prepared by physical mixing (PM) and freeze drying (FD) and were characterized by infrared spectroscopy, thermal analysis, scanning electron microscopy and X-ray diffraction. The characterization of the complexes in solution was performed by phase solubility analysis (PSA). The antimicrobial activity was evaluated by determining the minimum inhibitory concentration (MIC) and fractional inhibitory concentration (FIC) and antibiofilm activity by the XTT assay.The results obtained by the different solid-state techniques confirmed the formation of an amorphous solid in the system obtained by FD, while the PM showed a behavior similar to the pure components. The PSA showed a significant increase in the aqueous solubility of CLM in the co-amorphous system. Synergism was also observed between both drugs against Staphylococcus aureus and antibiofilm activity against this bacterium was significantly increased.The binary combination CLM:NAC had a better dissolution profile than the pure drug. In addition, the antimicrobial activity of CLM against S. aureus it was increased both, in planktonic state and when it was forming biofilms. Accordingly, it can be concluded that said combination is potentially useful for application in a future pharmaceutical formulation.