Abstract
Unknown impurities were detected during Photo degradation of Olopatadine Hydrochloride ophthalmic solution 0.5% (w/v) when analyzed using the High performance liquid chromatographic technique with Photo Diode Array Detection. For further investigation was carried out by isolating these impurities from impurity rich sample of Olopatadine Hydrochloride ophthalmic solution 0.5% (w/v) using preparative isolation technique. The Olopatadine Hydrochloride ophthalmic solution 0.5% (w/v) was subjected to photolytic forced degradation in the presence of Benzalkonium chloride and other excipients like Hypromellose, Mannitol, Hydroxypropyl, Boric acid, Kollidon 30 LP and mixture of solvents (Acetonitrile: Methanol; 1: 1 (v/v) under Ultra violet visible light. This led to the formation of the said impurities in higher concentration. This sample was then subjected to preparative HPLC for isolation of these unknown impurities. The structure of these unknown impurities was further elucidated using a different technique like Infra Ray Spectroscopy, Direct infusion (DI) Mass Spectroscopy, Ultra violet-Visible Spectroscopy, Proton Nuclear Magnetic Resonance Spectroscopy, carbon Nuclear Magnetic Resonance and Distortionless Enhancement by Polarization Transfer (DEPT) Spectroscopy which helped to confirm the structure of the impurities. Structure elucidation of the two impurities revealed that these are E and Z isomers of the Olopatadine hydrochloride Carbaldehyde. Olopatadine Z- isomer is used in the formulation of the Olopatadine Hydrochloride Ophthalmic Solution 0.5% (w/v). The minor amount of E- isomer also remains present in this solution as a potential impurity. However, the amount of E-isomer may increase in the solution form due to racemization. Hence, the respective Carbaldehyde impurities (both E and Z isomers) are forming during Photolytic degradation. This formation is happening through photolytic Norrish type-1 reaction which is elaborated in the paper.
Highlights
Olopatadine Hydrochloride is selective histamine H1 receptor antagonist and an inhibitor of the release of mediators including histamine from the human mast cells
Wide range of literature is available regarding related substances of Olopatadine Hydrochloride and most of these related substances are available in the market commercially, but none of them corresponds to the potential photodegradation impurities of Olopatadine Hydrochloride and comprehensive study was undertaken for isolation and identification of photodegradation impurities of Olopatadine Hydrochloride ophthalmic solution 0.5% (w/v) [9,10]
It was decided to scan the peak of an impurity using Photo Diode Array detector to get characteristic Ultra violet spectra which would be helpful during preparative isolation
Summary
Olopatadine Hydrochloride is selective histamine H1 receptor antagonist and an inhibitor of the release of mediators including histamine from the human mast cells. Since the impurity profile study of any pharmaceutical substance is a crucial part of process development, it was felt necessary to develop a reliable, High-Performance Liquid Chromatography method for identification and quantitative determination of impurities in Olopatadine Hydrochloride. [7] A comprehensive study was undertaken for the identification of these impurities by isolation using preparative HPLC and further characterization by various spectroscopic techniques. Wide range of literature is available regarding related substances of Olopatadine Hydrochloride and most of these related substances are available in the market commercially, but none of them corresponds to the potential photodegradation impurities of Olopatadine Hydrochloride and comprehensive study was undertaken for isolation and identification of photodegradation impurities of Olopatadine Hydrochloride ophthalmic solution 0.5% (w/v) [9,10]
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