Improving stability of chloramphenicol eye drops via vehicle compositions

Abstract

Chloramphenicol eye drops were prepared to decrease hydrolysis by adjusting the vehicle to optimum pH and obtaining a suitable buffer system. Various concentrations of HPMC 4000 and PVP K90 were to increase the viscosity. Partial replacement of water with cosolvent of low dielectric constant was also conducted using different concentrations and different molecular weights of PEGs. Solubilisation of chloramphenicol by non-ionic surfactant, poloxamer₄₀₇ also performed. Tonicity, pH, viscosity and discoloration were to select formulations suitable for eye drops. Accelerated thermodegradation process was performed at temperatures of 40°, 50°, 55°and 60℃ for stability testing. The content of intact chloramphenicol was assayed by reverse phase High Performance Liquid Chromatography and propylparaben as an internal standard. The degradation of the drug was first ordered kinetic. The reaction rate was linearly correlated to absolute temperature in Arrhenius relationship (r² = 0.9924 – 0.9996). The heat of activation was found to be in the range of 20-30 k.cal/mol. Adjusting the pH to 6.0 did not improve the stability. So did the HPMC and PVP at the experimental concentrations. Both additives increased viscosity, slightly increased the tonicity and did not change the pH. However, PVP was observed discoloration. PEG markedly improved the stability. However, it was not concluded that the more increasing of concentration, the more stability occurred and the higher molecular weight of PEG stated more stability than the lower molecular weight of PEG. PEG increased viscosity and produced high tonicity especially at higher concentrations. Moreover, the concentration of PEG linearly related to the logarithm of tonicity (r² ) 0.9877). Conversely, PEG’s of higher molecular weight increased the tonicity less than those of lower molecular weight. PEG’s did not change the pH but darkened the color especially at high concentration. Fifteen percentages of poloxamer₄₀₇ gave the best stability of chloramphenicol. Its calculated shelf-life was 47.68% longer than chloramphenicol eye drops BPC 1973. Its shelf-life according to the standard of BP 1980 at 25℃ was 11.80 months (7.09-19.65) and 21.62 months (12.98-35.99) according to the standard of USP XXI. Poloxamer₄₀₇ moderately increased the tonicity, did not change the pH and slightly discoloration.