Stability Study of Darunavir Ethanolate Tablets Applying a New Stability-Indicating HPLC Method

Josilene Chaves Ruela Corrêa,Cristina Helena Dos Reis Serra,Hérida Regina Nunes Salgado

doi:10.1155/2013/834173

Josilene Chaves Ruela Corrêa, Cristina Helena Dos Reis Serra + Show 1 more

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https://doi.org/10.1155/2013/834173

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Abstract

Chemical and physical degradation of drugs may result in altered therapeutic efficacy and even toxic effects. Therefore, the aim of this work was to study the stability of darunavir and to develop and validate a liquid chromatography (LC) method to determine darunavir in raw material and tablets in the presence of degradation products. The novel method showed to be linear from 6.0 to 21.0 μg/mL, with high precision (CV < 2%) and accuracy (recuperation of 99.64%). It is simple and reliable, free of placebo interferences. The robustness of the method was evaluated by a factorial design using seven different parameters. Forced degradation study was done under alkaline, acidic, and oxidative stress at ambient temperature and by heating. The LC method was able to quantify and separate darunavir and its degradation products. Darunavir showed to be unstable under alkaline, acid, and oxidative conditions. The novelty of this study is understanding the factors that affect darunavir ethanolate stability in tablets, which is the first step to unravel the path to know the degradation products. The novel stability-indicating method can be used to monitor the drug and the main degradation products in low concentrations in which there is linearity.

Highlights

According to the World Health Organization (WHO) AIDS epidemic updates, in 2009 new HIV infections were reduced by 17% over the previous eight years
To evaluate all samples in this study, we have developed an accurate, simple and reliable stability-indicating high-performance liquid chromatography (HPLC) method free of placebo interferences
The HPLC method used to confirm the purity and to standardize the raw material against the chemical reference was that described by Goldwirt and coworkers [14], whereupon the darunavir peak surface represented 96.6% of the total chromatogram surface area and it contains 94% of darunavir when analyzed against darunavir chemical reference

Summary

Introduction

According to the World Health Organization (WHO) AIDS epidemic updates, in 2009 new HIV infections were reduced by 17% over the previous eight years. Data from WHO show that there are more people living with HIV than ever before as people are living longer due to the beneficial effects of antiretroviral therapy along with population growth [1]. As an important component of the HAART, darunavir (Figure 1), a synthetic nonpeptidic protease inhibitor developed by the pharmaceutical company Tibotec in 1998 [3], has demonstrated high efficacy against HIV [4, 5]. This compound was licensed in June 2006 in the United States and in February 2007 in the European Union [1]. The daily dose of darunavir (600 mg twice a day) has to be administered along with low dose (100 mg) of ritonavir as a booster and food [6] which contributes to better solubilization of the drug in the lumen [6]

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