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Stress Degradation Studies of Irbesartan and Hydrochlorothiazide and Development of Validated Stability Indicating Method

Moin Shakeb1*, SB Puranik2 and Swamy Sreenivasa3

1Research Scholar, & Research Guide Bundelkhand University, Jhansi, Madhya Pradesh, India

2Research Scholar, & Research Guide Bundelkhand University, Jhansi, Madhya Pradesh, India

3Prof. C. N. Rao Center for Advanced Materials, Department of Chemistry, Tumkur University, Tumkur-572 103, Karnataka, India

*Corresponding Author:
Moin Shakeb
Research Scholar, & Research Guide Bundelkhand University, Jhansi, Madhya Pradesh, India

Received date: 18/08/2014; Revised date: 12/09/2014; Accepted date: 16/09/2014

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Abstract

Irbesartan and Hydrochlorothiazide were subjected to different ICH prescribed stress conditions like acidic, alkaline, oxidation, reduction, thermal and photo stability condition and found that degraded peaks did not interfere with the peaks of drug under the study. A HPLC system LC Shimadzu UFLC-2000 Prominance LC- 20AD Binary Gradient System. SPDM 20A detector with Rheodyne injector and EnableC18 G column 250x 4.6mm, 5μm. Injection volume of 20μL was injected and eluted with the mobile phase consists of a mixture of 50mM Ammonium acetate: Acetonitrile (70:30% v/v) effluent was monitored at 235 nm using PDA detector. The method was linear over the concentration range of 150-350μg/ml (r2 = 0.999) with a limit of detection and quantitation of 0.019 and 0.053μg /ml for Irbesartan, and range of 15-35μg/ml (r2 = 0.999) with a limit of detection and quantitation of 0.023 and 0.070μg/ml for Hydrochlorothiazide The method was validated for linearity, range, precision, accuracy, specificity, selectivity and intermediate precision.

Keywords

HPLC, Irbesartan, Hydrochlorothiazide, Stress degradation studies

Introduction

Pharmaceutical chemists have to rely on forced degradation samples to develop SIMs [1-4]. The ability of forced degradation studies (also called stress studies) to forecast real-time degradation has been the object of several studies.

Drug Profiles [7-8]

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Formal stability assessment of pharmaceuticals is typically done at three distinct times during development and commercialization: during development, to support the safety and efficacy claims of investigational new drugs; at registration, to ascertain the quality and shelf-life of the marketed product and its ingredients; and finally during the commercialization phase, to ensure the quality of the production and to support site or other changes to the product. Stability information on both drug substance and drug products is required as part of the registration dossier and serves to assign/confirm the shelf-life, determine appropriate storage conditions, define supply chain management, and assure that the quality of the product is unchanged from the time of manufacture to the time of administration to the patient.

Materials and Method [5-6]

A stability indicating HPLC method for simultaneous estimation of Telmisartan and Hydrochlorothiazide was developed and validated. The chemicals were Acetonitrile; HPLC grade was procured from (Sd Fine-Chem Ltd), Ammonium acetate, AR grade, Millipore water, Irbesartan (Hetero Pharma), Hydrochlorothiazide (Aurobindo Pharma) and The tablets Xarb- H was manufactured by Piramil Health care Pvt Ltd, India. Were procured from local market.

Forced Degradation Studies for Irbesartan and Hydrochlorothiazidec

Forced degradation studies for Irbesartan and Hydrochlorothiazide were carried out in acidic, alkaline, oxidation, thermal and in UV condition.

Degradation Studies of Irbesartan and Hydrochlorothiazide in Acidic Condition

Forced degradation studies for Irbesartan (100 μg/mL) and Hydrochlorothiazide (100 μg/mL) were carried out in 0.1N HCl at room temperature for a period of 4 hrs, and at 60°C for 1 hr.

The acidic degradation of standard Irbesartan drug in 0.1 N HCl was found to be 31.94% at (60°C)1 hour giving rise to a degraded peak at a retention time of 9.5 min. Whereas the degradation of Hydrochlorothiazide in 0.1 N HCl was found to be 30.02% at (60°C) 1hr giving rise to a degraded peak at a retention time of 3.1 min

Degradation Studies of Irbesartan and Hydrochlorothiazide in Alkaline Condition

Forced degradation for Irbesartan and Hydrochlorothiazide were carried out in 0.1N NaOH at room temperature for a period of 4 hrs, and at 60°C for 1 hr. The alkaline degradation of standard Irbesartan was found to be 18.41% degraded in 0.1N NaOH at(60°C) 1 hr giving rise to a degraded peak at the retention time of 9.49 min. Where as the degradation of standard drug Hydrochlorothiazide in alkaline medium was found to be 35.63 % degraded in 0.1N NaOH at 6th hr giving rise to a degraded peak at the retention time of 3.07 min.

Degradation Studies of Irbesartan and Hydrochlorothiazide in Oxidation Condition

Forced degradation for Irbesartan and Hydrochlorothiazide were carried out in 3% Hydrogen peroxide. The oxidation degradation of standard Irbesartan was found to be stable. Whereas the degradation of standard drug Hydrochlorothiazide in oxidation condition was found to be 20.59% degraded in oxidation condition at 2nd hr, 33.91% at 4 th hr giving rise to a degraded peak at the retention time of 1.9 min.

Degradation Studies of Irbesartan and Hydrochlorothiazide in Thermal Condition at 60°C

Thermal degradation studies for Irbesartan and Hydrochlorothiazide was carried out in hot air oven at 60°C for two days. Thermal degradation of standard drug Irbesartan and Hydrochlorothiazide was found to be stable for 48 hr after exposing the drug to 60°C in hot air oven with no degradation peaks.

Degradation Studies of Irbesartan and Hydrochlorothiazide in Photo stability Condition

Photo stability degradation study for Irbesartan and Hydrochlorothiazide were carried out in Photo stability chamber by exposing to UV light for 48 hrs. The data obtained is presented below Photolytic degradation of standard drug Irbesartan and Hydrochlorothiazide was found to be stable for 48 hr after exposing the drug to UV light with no degradation peaks.

Results and Discussion [9-14]

Separation Studies

A stability indicating HPLC method was developed for the simultaneous estimation of Irbesartan and Hydrochlorothiazide using a c18 column (Enable C-18 G, 250 mm x 4.6 mm, 5 μm), mobile phase consisting of Acetonitrile : Ammonium acetate buffer (pH: 5.5) in ratio of 30:70 flow rate of 1.5 mL/ min, PDA detection at wavelength of 235 nm. The retention time of Irbesartan and Hydrochlorothiazide was observed at 7.1 and 3.3 min respectively. The developed method was then validated by using various parameters like accuracy, precision, linearity, specificity, ruggedness and robustness etc as per ICH guidelines and reported in Table No. 1

pharmaceutics-nanotechnology-Validation-Parameters

Table 1: Validation Parameters of the HPLC Method [5-6]

The objective of the proposed project was to develop and validate a Stability indicating HPLC for simultaneous estimation of Irbesartan and Hydrochlorothiazide in bulk drugs marketed formulation and to carry out the forced degradation of the drugs and study the effect of degraded products on the development method.

Forced degradation studies was carried out at different stress conditions like acidic, alkali, oxidation, thermal, and photolytic condition for Irbesartan and Hydrochlorothiazide, and to study whether the degraded products interferes with the method and the results were presented in Table No. 2.

pharmaceutics-nanotechnology-Forced-Degradation-Studies

Table 2: Forced Degradation Studies for Irbesartan and Hydrochlorothiazide.

In Acidic Condition standard drug of Irbesartan and Hydrochlorothiazide was found to be 31.04% and 30.02% degraded at 1st hour of 60°C.

In Alkaline Condition standard drug of Irbesartan and Hydrochlorothiazide was found to be 18.41% and 35.63% degraded at 1st hour of 60°C

In Oxidative Condition standard drugs of Irbesartan was found to be stable and Hydrochlorothiazide was found to be 20.59% degrade at 2nd hr, 33.91% degraded at 4th hour.

In Thermal Studies standard drugs of Irbesartan and Hydrochlorothiazide were found to be stable at 60°C for 48 hr.

In Photo stability Studies standard drugs Irbesartan and Hydrochlorothiazide were found to be stable after 48 hr.

From the degradation studies data, it was found that Irbesartan and Hydrochlorothiazide was found to be degraded in all stress conditions. And there is no interference of degraded peaks with the standard drug peaks.

Hence stress testing should be given importance for such combination of drugs and quantification of degraded products of such drugs helps us to maintain the quality, safety and efficacy of drugs in formulations.

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