scholarly journals Perspectives in modeling and model validation during analytical quality by design chromatographic method evaluation: a case study

AAPS Open ◽  
2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yongzhi Dong ◽  
Zhimin Liu ◽  
Charles Li ◽  
Emily Pinter ◽  
Alan Potts ◽  
...  
Keyword(s):  
Quality By Design ◽  
Hplc Method ◽  
Original Method ◽  
Analytical Quality ◽  
Method Evaluation ◽  
Phase Gradient ◽  
Solid Models ◽  
Development And Validation ◽  
And Control

AbstractDesign of experiments (DOE)-based analytical quality by design (AQbD) method evaluation, development, and validation is gaining momentum and has the potential to create robust chromatographic methods through deeper understanding and control of variability. In this paper, a case study is used to explore the pros, cons, and pitfalls of using various chromatographic responses as modeling targets during a DOE-based AQbD approach. The case study involves evaluation of a reverse phase gradient HPLC method by a modified circumscribed central composite (CCC) response surface DOE.Solid models were produced for most responses and their validation was assessed with graphical and numeric statistics as well as chromatographic mechanistic understanding. The five most relevant responses with valid models were selected for multiple responses method optimization and the final optimized method was chosen based on the Method Operable Design Region (MODR). The final method has a much larger MODR than the original method and is thus more robust.This study showcases how to use AQbD to gain deep method understanding and make informed decisions on method suitability. Discoveries and discussions in this case study may contribute to continuous improvement of AQbD chromatography practices in the pharmaceutical industry.

scholarly journals Analytical quality by design approach to RP-HPLC method development and validation for simultaneous estimation of esomeprazole and naproxen in modified-release dosage form

2022 ◽  
Vol 8 (1) ◽  
Author(s):  
Khandokar Farjana Urmi ◽  
Md. Saddam Nawaz ◽  
S. M. Ashraful Islam
Keyword(s):  
Dosage Form ◽  
Method Development ◽  
Quality By Design ◽  
Hplc Method ◽  
Simultaneous Estimation ◽  
Solution Stability ◽  
Modified Release ◽  
Analytical Quality ◽  
Rp Hplc ◽  
Development And Validation

Abstract Background The present work describes the development and validation of a new, specific, accurate, and precise stability-indicating RP-HPLC method for the simultaneous estimation of Esomeprazole (ESP) and Naproxen (NAP) in modified-release bi-layer tablet dosage form. Analytical Quality by Design concept was implemented through the method development exercise to establish the robustness of the method. Results Method development was performed on C18, 250 × 4.6 mm ID, and 5 µm particle size column with 10 µl injection volume using a photodiode array (PDA) detector to monitor the detection at 280 nm. The mobile phase consisted of the buffer: methanol at a ratio of 50: 50 (v/v), and the flow rate was maintained at 1.5 ml/min, and the column oven temperature was maintained at 30 °C. The retention times for NAP and ESP were found 5.9 ± 0.1 and 8.9 ± 0.1 min, respectively. The method was validated in terms of system suitability, specificity, accuracy, linearity, precision, and solution stability. Linearity was observed over the range of concentration 8–12 µg/ml for ESP and 200–300 µg/ml for NAP, and the correlation coefficient (R2) was found excellent > 0.999. The method was specific to ESP and NAP, and the peak purity was found 99.97% for ESP and 100.00% for NAP. The method was precise and had %RSD less than 2. Recovery study for accuracy with placebo was found in the range of 99.63–100.36% for ESP and 99.91–100.43% for NAP. Conclusion This proposed fast, reliable, cost-effective method can be used as a quality control tool for the simultaneous determination of Esomeprazole and Naproxen in routine laboratory analysis. Graphical Abstract

scholarly journals QbD approach to HPLC method development and validation of ceftriaxone sodium

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Krunal Y. Patel ◽  
Zarna R. Dedania ◽  
Ronak R. Dedania ◽  
Unnati Patel
Keyword(s):  
Mobile Phase ◽  
Method Development ◽  
Quality By Design ◽  
Hplc Method ◽  
Design Expert ◽  
Ceftriaxone Sodium ◽  
Method Development And Validation ◽  
Hplc Method Development ◽  
Development And Validation ◽  
Central Composite

Abstract Background Quality by design (QbD) refers to the achievement of certain predictable quality with desired and predetermined specifications. A quality-by-design approach to method development can potentially lead to a more robust/rugged method due to emphasis on risk assessment and management than traditional or conventional approach. An important component of the QbD is the understanding of dependent variables, various factors, and their interaction effects by a desired set of experiments on the responses to be analyzed. The present study describes the risk based HPLC method development and validation of ceftriaxone sodium in pharmaceutical dosage form. Results An efficient experimental design based on central composite design of two key components of the RP-HPLC method (mobile phase and pH) is presented. The chromatographic conditions were optimized with the Design Expert software 11.0 version, i.e., Phenomenex ODS column C18 (250 mm × 4.6 mm, 5.0 μ), mobile phase used acetonitrile to water (0.01% triethylamine with pH 6.5) (70:30, v/v), and the flow rate was 1 ml/min with retention time 4.15 min. The developed method was found to be linear with r2 = 0.991 for range of 10–200 μg/ml at 270 nm detection wavelength. The system suitability test parameters, tailing factor and theoretical plates, were found to be 1.49 and 5236. The % RSD for intraday and inter day precision was found to be 0.70–0.94 and 0.55–0.95 respectively. The robustness values were less than 2%. The assay was found to be 99.73 ± 0.61%. The results of chromatographic peak purity indicate the absence of any coeluting peaks with the ceftriaxone sodium peak. The method validation parameters were in the prescribed limit as per ICH guidelines. Conclusion The central composite design experimental design describes the interrelationships of mobile phase and pH at three different level and responses to be observed were retention time, theoretical plates, and peak asymmetry with the help of the Design Expert 11.0 version. Here, a better understanding of the factors that influence chromatographic separation with greater confidence in the ability of the developed HPLC method to meet their intended purposes is done. The QbD approach to analytical method development was used for better understanding of method variables with different levels.

APPLICATION OF QUALITY BY DESIGN (QBD) APPROACH TO THE DEVELOPMENT OF A CYTOPHEROMETRIC ANALYTICAL METHOD OF HUMAN RED BLOOD CELLS: COMPARISON WITH TRADITIONAL DEVELOPMENT METHODOLOGY

2020 ◽  
pp. 237-256
Author(s):  
Fernando Ferrandiz Vindel
Keyword(s):  
Analytical Methods ◽  
Quality By Design ◽  
Drug Analysis ◽  
Human Red Blood Cells ◽  
Process Understanding ◽  
Physico Chemical ◽  
Scope Of Application ◽  
Product And Process ◽  
Development And Validation ◽  
And Control

Quality by Design (QbD) is defined as a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management, according to ICH Q section guidelines definition. Although this definition does not specifically mention analytical methods, since 2007 there have been authors who have defended the possibility of applying the principles of QbD to the development and validation of analytical methods in order to ensure their ruggedness and robustness, especially in the field of physical and physicochemical methods related to the quantitative drug analysis. However, in our experience, the real scope of application of QbD for analytical methods can include not only the quantitative analysis of drugs, but also other analytical methods in which other properties are determined, such as cytoferometry, a specific type of cell and particle suspension electrophoresis, with which it is possible to determine the electrophoretic mobility of normal and pathological erythrocytes. Data of the original development of a cytopherometric method carried out in 1988 have been reprocessed according to current QbD principles, and the results obtained with the traditional methodology and with the QbD methodology have been compared. This comparison demonstrates that the results processed following QbD show an enhancement in the knowledge and control of the cytopherometric method, giving more flexibility on physical and physico-chemical parameters management and appropriate tools to control the principal sources of analytical variability.

Sign in / Sign up

Export Citation Format

Share Document