Desenvolvimento de uma formulação para limpeza de lentes de contato contendo ácido gálico

Abstract

The use of contact lenses is associated with ocular complications, such as microbial keratitis, whose main cause is the formation of bacterial biofilms that hinder the action of antimicrobial agents and increase microbial resistance. In this context, this study developed and evaluated a cleaning solution containing gallic acid (GA), a phenolic compound with antimicrobial properties. Three solutions were formulated (F1: 0.01%, F2: 0.05%, F3: 0.10%) containing GA and 0.02% benzalkonium chloride (BC), along with a placebo (FP). The process followed the principles of Quality by Design (QbD), allowing strict control of critical development variables. The compatibility between components was assessed through thermal analysis (DTA/TG), while the physicochemical stability was monitored for 180 days under different conditions (4°C, 25°C, and 40°C with 75% humidity). The irritant potential was determined using the hemolysis assay in human red blood cells. Preservative efficacy was evaluated according to the standards of the Brazilian Pharmacopoeia, 6th edition, while antimicrobial activity was determined using MIC, MMC, and agar diffusion tests against S. aureus, E. coli, P. aeruginosa, and C. albicans. The QbD process results indicate that the final formulation met the established requirements and ensured product quality and reliability, preventing issues such as excessive foam formation and guaranteeing proper component dissolution. The interaction between GA and BC did not compromise the thermal stability of the formulation, ensuring no component degradation. Long-term stability tests demonstrated that the formulations maintained their pH and physicochemical characteristics unchanged over 180 days at room temperature and under refrigeration. In the hemolysis assay, F1 showed a hemolysis rate of 23.62%, within acceptable limits for ocular application, while F2 and F3 exhibited high toxicity (>80%), suggesting that higher GA concentrations may compromise formulation safety. Preservative efficacy tests indicated that formulation F1 at dilution C-1 (GA = 50 µg/mL and BC = 100 µg/mL) showed greater efficacy in inhibiting the growth of all tested microorganisms, meeting the requirements established by the Brazilian Pharmacopoeia. Microbiological evaluation revealed that F1 exhibited significant antimicrobial activity against the tested microorganisms, with MIC values of 0.39 µg/mL and MMC of 3.125 µg/mL for S. aureus, MIC of 0.78 µg/mL and MMC of 6.25 µg/mL for E. coli, and MIC of 1.56 µg/mL and MMC of 25 µg/mL for P. aeruginosa and C. albicans, demonstrating that the formulation was able to eliminate pathogens at relatively low concentrations. These results were reinforced by the agar diffusion assay, in which F1 showed inhibition halos of 10 mm for S. aureus, 9.5 mm for E. coli, 8.0 mm for P. aeruginosa, and 10 mm for C. albicans. Therefore, data analysis suggests that formulation F1 represents a balance between antimicrobial efficacy and safety. The combination of GA and BC demonstrated a synergistic effect. Thus, the developed formulation emerges as an innovative and viable alternative for contact lens cleaning, contributing to the prevention of biofilm formation and ocular infections.