Isolation and Characterization Photo Degradation Impurities of Drug Product Olopatadine Hydrochloride by Spectral Techniques
Shivaji Jadhav,
Amit Gosar,
Amit Jadkar,
Rajesh Ankam,
Chandrakant Dhatrak
Issue:
Volume 4, Issue 2, June 2019
Pages:
31-36
Received:
8 April 2019
Accepted:
28 May 2019
Published:
17 June 2019
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.
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 Hydrochlori...
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The Method of Obtaining Interfacial Catalysis Azerbaijan State University of Oil and Industry
Mikayilova Mehriban Rahil,
Mustafayeva Rena Eldar
Issue:
Volume 4, Issue 2, June 2019
Pages:
37-39
Received:
3 April 2019
Accepted:
13 June 2019
Published:
26 June 2019
Abstract: Since the reaction proceeds very smoothly under these conditions, the main products are obtained in high yields, including with a high degree of frequency. Increasing the amount of DB18K6 from 0.001 to 0.004 moll and carrying out the reaction at a temperature of 1000°C for 70 minutes in the system: 1, 2 dimethyl cyclohexane, KOH (0.4 moll), dioxin leads to a gradual increase in the yield of methyl cyclohexane. The maximum yield is achieved with the use of 0.004 moll DB18K6. Secondly, carrying out the reaction at 130°C (against 250°C) excluded the formation of by-products, as well as the products of isomerization and tarification. An organic compound of composition C12H24O6, belonging to the class of cyclic ethers (crown ethers) and having in a single cycle 6 oxygen atoms arranged in a symmetric manner. It is a white hygroscopic crystal with a low melting point. It is widely used as a specific complexing agent for potassium ions K+. Used reducing agents in a homogeneous medium. Restored ketones in boiling xylene or toluene in the presence of ekvimolar amounts of catalysts, which contributed to the increase in solubility. Diglime, dimethoxymethane and dibenzo-18-crown-6 were used as catalysts. The last of them leads to better results, however, due to the occurrence of side condensation reactions, the yields of the target products are mediocre. Solid or oily substances form stable complexes with salts (alkali and alkali-metal) soluble in organic solvent. The most commonly used are 18-cray-6, dibenzo-18-crown-6 and the hydrogenation product of the latter - dicyclohexylene-18-crown-6. Studying the influence of various factors, it was found that when using potassium hydroxide (0.4 moll) in xylene at a temperature of 130°C in the presence of dibenzo-18-crown-6 (DB18K6) (0.0004 moll), the yield of methyl cyclohexane reaches 90 98%.
Abstract: Since the reaction proceeds very smoothly under these conditions, the main products are obtained in high yields, including with a high degree of frequency. Increasing the amount of DB18K6 from 0.001 to 0.004 moll and carrying out the reaction at a temperature of 1000°C for 70 minutes in the system: 1, 2 dimethyl cyclohexane, KOH (0.4 moll), dioxin ...
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