(T1530-07-39) Overcoming Incompatibility between Moxifloxacin and Carbopol^®934 Polymers in Ophthalmic Drug Delivery Systems

Purpose: In our previous investigation, Carbopol^® 934, used as a mucoadhesive agent in topical ocular drug delivery applications, was incorporated into a Moxifloxacin (MOX) loaded nanoemulsion to extend the drug's ocular residence time. However, a yellow precipitate formed at the bottom of the container during preparation. This study aims to overcome the observed incompatibility between MOX and Carbopol^® 934.

Methods: The reaction between MOX and Carbopol^® 934 polymer was initiated at a 1:1 ratio. In vitro release-diffusion study of the MOX-Carbopol^® 934 complex was performed using the dialysis method. Different salts were selected to assess their ability to dissolve the MOX-Carbopol^® 934 complex. The MOX content of solutions of dissolved complex, post-salt addition, was determined using a validated HPLC method. Also, the volume of salt solution required to dissolve the MOX-Carbopol^® 934 complex and resulting osmolality were determined.

Results: The in vitro release-diffusion profile of the MOX-Carbopol^® 934 complex showed hardly any release of MOX, even after 24 hours at pH 7.4. Interestingly, only four of the tested salts were able to dissolve the MOX-Carbopol^®934 complex completely, with final pH values ranging from 5.08 to 7.85. The MOX content in solution following the addition of three basic salts (Na₂HPO₄.2H₂O, KHCO₃, or NaHCO₃) to the MOX-Carbopol^® 934 complex ranged from 97-103%, demonstrating complete disruption of the MOX-Carbopol^® 934 complex. The neutral salt (NH₄CH₃COOH), however, did not fully dissolve/disrupt the complex, with only 87% MOX in solution. The osmolality of the MOX-Carbopol^® 934 reaction mixture increased with the addition of NaHCO₃, KHCO₃, and NaH₂PO₄.2H₂O, however, it remained within the acceptable range for ocular applications.

Conclusion: The MOX-Carbopol^® 934 complex showed no release of MOX even after 24 hours. This release limitation is attributed to the strong interaction between the cationic amine of MOX and the anionic carboxylic group of Carbopol^® 934 within the complex. The ability of the basic salts (Na₂HPO₄.2H₂O, NaHCO₃, and KHCO₃) to prevent/disrupt the MOX-Carbopol^® complex formation will be a focus for future studies incorporating Carbopol^® polymers into MOX-containing topical ocular formulations.

Figure 1. In vitro release-diffusion profile of Moxifloxacin (MOX) from control solution (0.5%) and MOX-Carbopol® 934 complex mixtures. The release-diffusion studies were carried out using a Thermo Scientific Slide-A-Lyzer™ MINI dialysis device (10 K MWCO). Data represents mean ± SD (n = 3).

Figure 2. The Moxifloxacin (MOX) content in solution following the addition of 2 mL of 1M of different salts solutions (Na2HPO4.2H2O, NaHCO3, KHCO3, and NH4CH3COOH) to 2 mL of MOX-Carbopol®934 (1:1) reaction mixture. Data represents mean ± SD (n = 3).

Table 1. pH and visual observations following the addition of 2 mL of nine salt solutions (1M) to MOX-Carbopol®934 (1:1) reaction mixtures.