QbD Approach Method Development for Estimation of Dabigatran Etexilate along with Its Impurities and Identification of Degradants in Capsule Dosage Form
| Autor: | Venkat Bhaskar Rao Pasagadugula, Woo Hyung Cho, Hanimi Reddy Bapatu, Ravi Kumar Maram |
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| Rok vydání: | 2016 |
| Předmět: |
Materials science
Central composite design Design of experiments 010401 analytical chemistry Analytical chemistry Factorial experiment 030226 pharmacology & pharmacy 01 natural sciences High-performance liquid chromatography Dosage form Quality by Design 0104 chemical sciences 03 medical and health sciences Psychiatry and Mental health chemistry.chemical_compound 0302 clinical medicine chemistry Forced degradation Ammonium formate |
| Zdroj: | American Journal of Analytical Chemistry. :494-524 |
| ISSN: | 2156-8278 2156-8251 |
| DOI: | 10.4236/ajac.2016.76047 |
| Popis: | The concept of Quality by Design was demonstrated in the development of a stability-indicating assay and related substances method by HPLC for Dabigatran Etexilate Capsules dosage form. Method design, method evaluation, method control and life cycle management were explained by systematic flow chart. Analytical Target Product profile was defined. The method was developed using the Inertsil ODS-3V, 150 mm × 4.6 mm, 5 μm column using the gradient program with ammonium formate buffer as mobile phase A and acetonitrile as mobile phase B. Risk assessment was performed as part of method evaluation. Design of experiment tools was used to optimize the chromatographic conditions. A two-level Full Factorial Design along with Face Centered Central Composite design augmentation was employed and statistical analysis of the experimental data uncovered the significant influential of chromatographic factors. The design space and the contour plot suggest that the current center point parameters can be further modified, resulting in better acceptability of the response parameters. The performance of the optimized method was validated according to current ICH guidelines. Dabigatran Etexilate Capsules was subjected to various stress conditions like oxidative, acid, base, hydrolytic, thermal, humidity, and photolytic degradations and evaluated chromatograms at 220 nm. The degradation products were well separated from each other and main peak, demonstrating the stability-indicating power of the method. One of the major degradant impurities, which are forming in neutral hydrolysis stress condition, is isolated and characterized by using analytical techniques like IR, LC-MS and NMR. Degradation pathway for Dabigatran Etexilate was proposed based on forced degradation data along with reaction mechanism. |
| Databáze: | OpenAIRE |
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