Isolation and Characterization Photo Degradation Impurities of Drug Product Olopatadine Hydrochloride by Spectral Techniques

Shivaji Jadhav; Amit Gosar; Amit Jadkar; Rajesh Ankam; Chandrakant Dhatrak

doi:doi:10.11648/j.cbe.20190402.11

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Isolation and Characterization Photo Degradation Impurities of Drug Product Olopatadine Hydrochloride by Spectral Techniques

Shivaji Jadhav, Amit Gosar, Amit Jadkar, Rajesh Ankam, Chandrakant Dhatrak

Published in Chemical and Biomolecular Engineering (Volume 4, Issue 2)

Received: 8 April 2019 Accepted: 28 May 2019 Published: 17 June 2019

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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.

Published in	Chemical and Biomolecular Engineering (Volume 4, Issue 2)
DOI	10.11648/j.cbe.20190402.11
Page(s)	31-36
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Isolation, Characterization, NMR, E and Z Isomers, Olopatadine Hydrochloride Ophthalmic Solution, Carbaldehyde Impurities

References

[1]	Tamura, T., 2012. Olopatadine ophthalmic solution suppresses substance P release in the Conjunctivitis models. Asia Pacific Allergy, 2 (2), pp. 115-121.
[2]	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.
[3]	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.
[4]	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.
[5]	Ahluwalia, V. K. (2009). Green chemistry: environmentally benign reaction. Ane Books Pvt Ltd.
[6]	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.
[7]	Guideline, I. H. T. (2006). Impurities in new drug products. Q3B (R2), current step, 4, 1-5.
[8]	United States Pharmacopeia, USP41–NF36. 2018. Olopatadine Hydrochloride ophthalmic solution.
[9]	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.
[10]	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.

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APA Style

Shivaji Jadhav, Amit Gosar, Amit Jadkar, Rajesh Ankam, Chandrakant Dhatrak. (2019). Isolation and Characterization Photo Degradation Impurities of Drug Product Olopatadine Hydrochloride by Spectral Techniques. Chemical and Biomolecular Engineering, 4(2), 31-36. https://doi.org/10.11648/j.cbe.20190402.11

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ACS Style

Shivaji Jadhav; Amit Gosar; Amit Jadkar; Rajesh Ankam; Chandrakant Dhatrak. Isolation and Characterization Photo Degradation Impurities of Drug Product Olopatadine Hydrochloride by Spectral Techniques. Chem. Biomol. Eng. 2019, 4(2), 31-36. doi: 10.11648/j.cbe.20190402.11

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AMA Style

Shivaji Jadhav, Amit Gosar, Amit Jadkar, Rajesh Ankam, Chandrakant Dhatrak. Isolation and Characterization Photo Degradation Impurities of Drug Product Olopatadine Hydrochloride by Spectral Techniques. Chem Biomol Eng. 2019;4(2):31-36. doi: 10.11648/j.cbe.20190402.11

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@article{10.11648/j.cbe.20190402.11,
  author = {Shivaji Jadhav and Amit Gosar and Amit Jadkar and Rajesh Ankam and Chandrakant Dhatrak},
  title = {Isolation and Characterization Photo Degradation Impurities of Drug Product Olopatadine Hydrochloride by Spectral Techniques},
  journal = {Chemical and Biomolecular Engineering},
  volume = {4},
  number = {2},
  pages = {31-36},
  doi = {10.11648/j.cbe.20190402.11},
  url = {https://doi.org/10.11648/j.cbe.20190402.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.cbe.20190402.11},
  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.},
 year = {2019}
}

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TY  - JOUR
T1  - Isolation and Characterization Photo Degradation Impurities of Drug Product Olopatadine Hydrochloride by Spectral Techniques
AU  - Shivaji Jadhav
AU  - Amit Gosar
AU  - Amit Jadkar
AU  - Rajesh Ankam
AU  - Chandrakant Dhatrak
Y1  - 2019/06/17
PY  - 2019
N1  - https://doi.org/10.11648/j.cbe.20190402.11
DO  - 10.11648/j.cbe.20190402.11
T2  - Chemical and Biomolecular Engineering
JF  - Chemical and Biomolecular Engineering
JO  - Chemical and Biomolecular Engineering
SP  - 31
EP  - 36
PB  - Science Publishing Group
SN  - 2578-8884
UR  - https://doi.org/10.11648/j.cbe.20190402.11
AB  - 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.
VL  - 4
IS  - 2
ER  -

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Author Information

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

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Plain Text BibTeX RIS

APA Style

Shivaji Jadhav, Amit Gosar, Amit Jadkar, Rajesh Ankam, Chandrakant Dhatrak. (2019). Isolation and Characterization Photo Degradation Impurities of Drug Product Olopatadine Hydrochloride by Spectral Techniques. Chemical and Biomolecular Engineering, 4(2), 31-36. https://doi.org/10.11648/j.cbe.20190402.11

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ACS Style

Shivaji Jadhav; Amit Gosar; Amit Jadkar; Rajesh Ankam; Chandrakant Dhatrak. Isolation and Characterization Photo Degradation Impurities of Drug Product Olopatadine Hydrochloride by Spectral Techniques. Chem. Biomol. Eng. 2019, 4(2), 31-36. doi: 10.11648/j.cbe.20190402.11

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AMA Style

Shivaji Jadhav, Amit Gosar, Amit Jadkar, Rajesh Ankam, Chandrakant Dhatrak. Isolation and Characterization Photo Degradation Impurities of Drug Product Olopatadine Hydrochloride by Spectral Techniques. Chem Biomol Eng. 2019;4(2):31-36. doi: 10.11648/j.cbe.20190402.11

Copy | Download

@article{10.11648/j.cbe.20190402.11,
  author = {Shivaji Jadhav and Amit Gosar and Amit Jadkar and Rajesh Ankam and Chandrakant Dhatrak},
  title = {Isolation and Characterization Photo Degradation Impurities of Drug Product Olopatadine Hydrochloride by Spectral Techniques},
  journal = {Chemical and Biomolecular Engineering},
  volume = {4},
  number = {2},
  pages = {31-36},
  doi = {10.11648/j.cbe.20190402.11},
  url = {https://doi.org/10.11648/j.cbe.20190402.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.cbe.20190402.11},
  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.},
 year = {2019}
}

Copy | Download

TY  - JOUR
T1  - Isolation and Characterization Photo Degradation Impurities of Drug Product Olopatadine Hydrochloride by Spectral Techniques
AU  - Shivaji Jadhav
AU  - Amit Gosar
AU  - Amit Jadkar
AU  - Rajesh Ankam
AU  - Chandrakant Dhatrak
Y1  - 2019/06/17
PY  - 2019
N1  - https://doi.org/10.11648/j.cbe.20190402.11
DO  - 10.11648/j.cbe.20190402.11
T2  - Chemical and Biomolecular Engineering
JF  - Chemical and Biomolecular Engineering
JO  - Chemical and Biomolecular Engineering
SP  - 31
EP  - 36
PB  - Science Publishing Group
SN  - 2578-8884
UR  - https://doi.org/10.11648/j.cbe.20190402.11
AB  - 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.
VL  - 4
IS  - 2
ER  -

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