The stability of piroxicam incorporated in a positively-charged submicron emulsion for ocular administration

Abstract

A comprehensive physicochemical characterization of a positively-charged submicron emulsion containing piroxicam was carried out in an attempt to identify optimal experimental conditions. An appropriate oil phase was selected from the results of the piroxicam solubility study of various oil and phase compositions containing piroxicam. Stable monodispersed positively-charged emulsions with a mean droplet size of 100 nm were obtained setting an adequate homogenization processing time. It was observed that after autoclave sterilization, a progressive reduction in pH occurred during the storage period, especially in the emulsions which were adjusted to an initial pH of 7.5 and stored at 37°C. The fall in pH was most probably due to the formation of free fatty acids (FFA), the origin of which should be attributed to chemical changes in the phospholipids present in the emulsion formulation. It was shown that the emulsion containing piroxicam was very sensitive to the adjusted initial pH and to the formation of FFA which reduced its pH over prolonged storage times. However, the decrease in pH did not appear to affect the zeta potential, which remained positive, and led to the precipitation of piroxicam, easily detected by visual and microscopic observations. As revealed by the monolayer studies, the drug was capable of interacting with the film-forming components which could explain the observed stability of the emulsions.