Influences of Polysorbate 80 Pretreatment Process on Related Substances in Pranoprofen Eye Drops

OBJECTIVE  To investigate the influence of the excipient polysorbate 80 and its pretreatment process on related substances in pranoprofen eye drops.

METHODS  A full factorial experimental design was utilized to analyze the effects of heating time and alkaline conditions during polysorbate 80 pretreatment on related substances. The interaction effects with other excipients during co-pretreatment were investigated. Meanwhile, a stability prediction model was established based on the Arrhenius equation.

RESULTS  Polysorbate 80 accelerated the formation of oxidative impurities in pranoprofen eye drops. The minimal impurity level was achieved when polysorbate 80 was co-treated with borax and disodium edetate for 2 h. The stability prediction model indicated that the optimized formulation could maintain stability for 36 months at 25 ℃.

CONCLUSION  When the formulation contains the excipient polysorbate 80, the formulation development process should be carried out in conjunction with the properties of the active pharmaceutical ingredient. If the active pharmaceutical ingredient is prone to oxidation, appropriate pre-treatment processes can be adopted to mitigate the impact of polysorbate 80 on related substances.