(T1530-04-24) Compatibility Study between Fluoroquinolones and Carbopol^® Polymers Used in the In Situ Gel Forming Delivery Systems

Purpose: In our earlier investigation, Carbopol^® 940 NF was added to a moxifloxacin-loaded nanoemulsion to prolong the ocular residence time of the drug; however, a yellow precipitate was observed at the bottom of the container during preparation. This study is aimed at understanding the drug–excipient compatibility between fluoroquinolones and the Carbopol^® gelling agents in terms of ocular drug delivery applications.

Methods: The reactions were initiated between three fluoroquinolones (moxifloxacin HCL (MOX), ciprofloxacin HCL (CPX), and levofloxacin (LVX) and two Carbopol^® polymers (Carbopol^® 940 NF and Carbopol^® 934 NF). Fluoroquinolones were used at concentrations approved for ocular delivery – MOX (0.54% w/v), CPX (0.35% w/v), and LVX (0.5% w/v). The compatibility studies were conducted with drug:Carbopol^® ratios of 1:1, 1:0.5, and 1:0.25. The supernatant was analyzed using HPLC for drug content following the complex formation. The pH of the suspension was changed in the upward and downward directions to investigate the effect of pH change on complex formation. Moreover, the formed complexes were characterized with Fourier Transform Infrared (FTIR) spectroscopy and Nuclear Magnetic Resonance (NMR) spectroscopy.

Results: All tested fluoroquinolone solutions exhibited turbidity on the addition of the two tested Carbopol^® polymers at all ratios studied. The complex formation was associated with a significant reduction in the fluoroquinolone content in the supernatant in comparison to Carbopol^®-free solutions. At ratio (1:1) MOX was the most affected amongst all tested fluoroquinolones with a percent drug content of 16.2 and 23.8, in the supernatant, in the presence of Carbopol^® 940 NF and Carbopol^® 934 NF, respectively. Then, LVX content percent was determined as 29.3 and 27.5 in case of Carbopol^® 940 NF and Carbopol^® 934 NF, respectively. Lastly, CPX showed the lowest content percent in the supernatant with Carbopol^® 940 NF and Carbopol^® 934 NF as 47.9 and 55.1, respectively. Furthermore, changing the pH of the reaction, within the pH range of 3.0–8.6,  converted LVX-containing complexes to clear solutions at a pH of 6.3. FTIR and NMR studies confirmed chemical incompatibility between fluoroquinolones and Carbopol^® polymers, which could be due to amide bond formation between the carboxylic and amine groups of polymer and fluoroquinolones, respectively.

Conclusion: Overall, the results demonstrated an incompatibility between the fluoroquinolones and Carbopol^® polymers studied.

Figure 1. Moxifloxacin hydrochloride content in solution in the presence of different concentration of Carbopol 934 NF and Carbopol 94o NF compared to control.


Figure 2. Levofloxacin content in solution in the presence of different concentration of Carbopol 934 NF and Carbopol 940 NF compared to control.



Figure 3. Ciprofloxacin hydrochloride content in solution in the presence of different concentration of Carbopol 934 NF and Carbopol 940 NF compared to control.