UHPLC Study on the Degradation Profiles of Olopatadine Hydrochloride in Eye Drops Subjected to Heat and Filtration Methods of Sterilisation

Abstract

A validated ultra-high performance liquid chromatography (UHPLC) method has been proposed, validated and used for the determination of olopatadine hydrochloride degradation products in olopatadine 1 mg mL−1 eye drops solution under the influence of two different sterilisation methods, heating and filtration, with good precision and accuracy. We found that the heat sterilization method yields a higher content of olopatadine hydrochloride degradation products in eye drops compared to unsterilized drug product or drug product sterilized by filtration, except for α-hydroxy olopatadine impurity, which remains stable with time and applied sterilization method. Contents of olopatadine related compound B shows a higher increase (from <0.005 to 0.044 %) when sterilised by heating than when subjected to aging and sterilization by filtration (increase up to 0.011 %). Similarly, total amount of all impurities is also increased from 0.13 to 0.49 % when the drug product is sterilised by heating instead of filtration (up to 0.39 %). Content of olopatadine related compound B and of all impurities is increased by aging, probably through thermal and oxidative degradation. Forced degradation studies were correlated with the sterilisation study and possible degradation pathways were identified. Olopatadine shows strong degradation under oxidative and moderate degradation under photolytic environment, with the olopatadine related compound B as the main degradation product. Sterilization of eye drops solution by filtration is recommended.