Isolation and Characterization Photo Degradation Impurities of Drug Product Olopatadine Hydrochloride by Spectral Techniques
Chemical and Biomolecular Engineering
Volume 4, Issue 2, June 2019, Pages: 31-36
Received: Apr. 8, 2019;
Accepted: May 28, 2019;
Published: Jun. 17, 2019
Views 731 Downloads 146
Shivaji Jadhav, Indoco Remedies Ltd, R & D Centre Rabale, Navi Mumbai, India
Amit Gosar, Indoco Remedies Ltd, R & D Centre Rabale, Navi Mumbai, India
Amit Jadkar, Indoco Remedies Ltd, R & D Centre Rabale, Navi Mumbai, India
Rajesh Ankam, Glenmark Pharmaceuticals Ltd, Nasik, India
Chandrakant Dhatrak, Glenmark Pharmaceuticals Ltd, Nasik, India
Follow on us
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.
Isolation, Characterization, NMR, E and Z Isomers, Olopatadine Hydrochloride Ophthalmic Solution, Carbaldehyde Impurities
To cite this article
Isolation and Characterization Photo Degradation Impurities of Drug Product Olopatadine Hydrochloride by Spectral Techniques, Chemical and Biomolecular Engineering.
Vol. 4, No. 2,
2019, pp. 31-36.
Copyright © 2019 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/
) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Tamura, T., 2012. Olopatadine ophthalmic solution suppresses substance P release in the Conjunctivitis models. Asia Pacific Allergy, 2 (2), pp. 115-121.
Abelson, M. B., & Welch, D. L. (2000). An evaluation of onset and duration of action of Patanol® (olopatadine hydrochloride ophthalmic solution 0.1%) compared to Claritin®(loratadine 10 mg) tablets in acute allergic conjunctivitis in the conjunctival allergen challenge model. Acta Ophthalmologica Scandinavica, 78, 60-63.
Maksić, J., Jovanović, M., Rakić, T., Popović, I., Ivanović, D., & Jančić-Stojanović, B. (2014). Chromatographic analysis of olopatadine in hydrophilic interaction liquid chromatography. Journal of chromatographic science, 53 (5), 680-686.
Limbachiya, U. N., Patel, N. N., Nikesh, R., KS, R., Patel, S., & Shinde, G. (2013). Analytical Method Development and Validation for Simultaneous Determination of Ambroxol and Olopatadine Hydrochloride in Synthetic Mixture. Asian Journal of Research in Chemistry, 6 (4), 389-392.
Ahluwalia, V. K. (2009). Green chemistry: environmentally benign reaction. Ane Books Pvt Ltd.
Mahajan, A. A., Mohanraj, K., Kale, S., & Thaker, A. K. (2013). STUDY OF OLOPATADINE HYDROCHLORIDE UNDER ICH RECOMMENDED STRESS CONDITIONS BY LC, LC-MS/TOF FOR IDENTIFICATION, AND CHARACTERIZATION OF DEGRADATION PRODUCTS. Journal of Liquid Chromatography & Related Technologies, 36 (13), 1881-1898. Kłos, K., Czerniec-Michalik, E.
Guideline, I. H. T. (2006). Impurities in new drug products. Q3B (R2), current step, 4, 1-5.
United States Pharmacopeia, USP41–NF36. 2018. Olopatadine Hydrochloride ophthalmic solution.
AlAani, H., & AlNukkary, Y. (2016). Determination of Benzalkonium Chloride in Ophthalmic Solutions by Stability-Indicating HPLC Method: Application to a Stability Study. Journal of Applied Pharmaceutical Science Vol, 6 (05), 080-089.
SAHOO, D. K., PATRO, S. S., & MOHAPATRA, S. METHOD DEVELOPMENT AND VALIDATION FOR THE ESTIMATION OF OLOPATADINE IN BULK AND PHARMACEUTICAL DOSAGE FORMS AND ITS STRESS DEGRADATION STUDIES USING UV-VIS SPECTROPHOTOMETRIC METHOD.