Darunavir Ethanolate Research Articles

Characteristics, Complexation and Analytical Methods of Darunavir

What is it? Darunavir is a protease inhibitor used in the treatment of HIV infection. It is an important drug of therapy cocktail for patients infected with the virus. On the market there are darunavir ethanolate tablets of 75, 150, 300, 400, 600 and 800mg, because this is the most stable form. It is commercialized by Janssen-Cilag with the name PrezistaTM.Why we started? This drug has low water solubility and poor bioavailability, therefore requires administration in doses relatively high to the success of the therapeutic effect. The complexation of drugs by using cyclodextrin is welcome in this respect to improve the solubility and hence increase the dissolution rate of poorly soluble drugs. A monograph about this compound has not been described, thus it is an extremely important quality control of darunavir to demonstrate its effectiveness and safety.What we did? Some existing analytical techniques have been discussed in this manuscript, focusing on bioanalytical and pharmaceutical quality control applications.What we found? This review showed the published analytical methods reported for the determination of darunavir and discuss about its characteristics and complexation with cyclodextrin.

Development and Validation of First Derivative Spectrophotometric Method for Quantification of Darunavir in Tablets

Aims: Darunavir is widely used in HIV/AIDS therapy. It is a HIV protease inhibitor that has excellent efficacyagainstthe virus.The aim of this study is to develop and validate an analytical method fast and free of interferences for determination of darunavir ethanolate as raw material and tablet dosage form. Methodology: As the formulation excipients show high interference in darunavir determination by adirect UV absorption measurement aderivative spectrophotometry was applied. Aselective, easy and fastmethod was achieved employing simple and cheap instrumentation by using first -order derivative spectrophotometry . Results:The first-derivation of spect rum of the drug measured between 200 and 400 nm allowed identification of the analyte and showed absence of placebo interference. The assay was based on the absorbance at 276nm.The linear concentration range was established from 11 to 21 �og/mL. The intra -day and inter-day precision expressed as RSD was 0.06% and 3.75% respectively with mean recovery of 99.84%. Conclusion: The proposed analytical method is able to quantify darunavir as raw material and tablets andcan be used routinely by any laboratory ap plying a spectrophotometer Original ResearchArticle

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

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.

Stability-Indicating HPLC Method for the Determination of Darunavir Ethanolate

A novel stability-indicating reversed-phase high-performance liquid chromatographic (HPLC) method has been developed for the quantitative determination of darunavir ethanolate, an HIV-1 protease inhibitor. The chromatographic separation was achieved using an X-Bridge C18 (150 × 4.6 mm × 3.5 µm) HPLC column in isocratic mode employing 0.01M ammonium formate (pH.3.0) buffer and acetonitrile in the ratio of 55:45 (v/v) with a flow rate of 1.0 mL/min. The detector wavelength was monitored at 265 nm and the column temperature was maintained at 30°C. Darunavir ethanolate was exposed to thermal, photolytic, acid, base and oxidative stress conditions. Considerable degradation of the drug substance was found to occur under acid, base and oxidative stress conditions. The peak homogeneity data of darunavir ethanolate obtained by photodiode array detection demonstrated the specificity of the method in the presence of degradants. The degradation products were well resolved from primary peak of darunavir, indicating that the method is specific and stability-indicating. The HPLC method was validated as per International Conference on Harmonization guidelines with respect to specificity, precision, linearity, accuracy and robustness. Regression analysis showed a correlation coefficient value greater than 0.999. The accuracy of the method was established based on the recovery obtained for darunavir ethanolate.

A simple and sensitive HPTLC method for quantitative analysis of darunavir ethanolate tablets

A quantitative high-performance thin-layer chromatography (HPTLC) method for determination of darunavir ethanolate (DRV) in tablets has been established and validated. DRV from the formulations was separated and identified on silica gel 60 F254 HPTLC plates with toluene-ethyl acetate-methanol 7.0:2.0:1.0 (ν/ν) as mobile phase. The plates were developed to a distance of 8 cm. Quantification was performed at λ = 267 nm. Well-resolved bands were obtained for DRV. The method was validated for specificity, precision, robustness, and accuracy. The calibration plot for DRV standard was linear in the range 250–1750 ng per band with r = 0.9994, slope = 0.4253, and intercept = 44.81. The limits of detection and quantification were 15.28 and 45.84 ng per band, respectively. The method is selective, sensitive, and specific, with potential application in pharmaceutical analysis.