Process Development and Optimization of Linagliptin Aided by the Design of Experiments (DoE)

Wang, Hailong; Chen, Kai; Lin, Biyue; Kou, Jingping; Li, Lijun; Wu, S. X.; Liao, Shouzhu; Sun, Guodong; Pu, Junwen; Ye, Hua; Wang, Zhongqing

doi:10.1021/acs.oprd.2c00230

Cited by 5 publications

(6 citation statements)

References 12 publications

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“…Due to these impurities, the maximum isolated yield obtained was about 65%. Optimization of reaction conditions tended to improve the conversion and selectivity using the design of experiments (DoE) − approach. In the DoE study, based on the risk assessment using fishbone analysis (Figure ), three critical parameters, mole equivalents of iodine, TMG, and reaction temperature, were identified.…”

Section: Resultsmentioning

confidence: 99%

Efficient Process Development of Abiraterone Acetate by Employing Design of Experiments

Komati,

Madhra,

Manda

et al. 2024

ACS Omega

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Section: Resultsmentioning

confidence: 99%

Efficient Process Development of Abiraterone Acetate by Employing Design of Experiments

Komati,

Madhra,

Manda

et al. 2024

ACS Omega

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“…Analysis of significant factors and interactions in DOEs: The analysis of significant factors and interactions involved determining which factors have a statistically significant impact on the response variable and how they interact with each other. The Pareto chart is a graphical tool used in the analysis of significant factors in the design of experiments (DOE) [37]. It is particularly useful in identifying and prioritizing the most influential factors affecting a response variable based on their relative importance.…”

Section: Figure 5 Tensiometer Applying Load To the Welded Geomembrane...mentioning

confidence: 99%

Optimization of Welding Process of Geomembranes in Biodigesters Using Design of Factorial Experiments

Camarena-Martinez,

Baeza-Serrato,

Lizarraga-Morales

2023

Energies

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This research focuses on the optimization of the thermofusion process in the construction of biodigesters as it has a direct influence on their quality and durability. The study utilizes factorial experiments and statistical analysis, with particular emphasis on the innovative application of the arcsine transformation. Two 2k factorial designs were developed to account for warm and cold weather. The experiments evaluated factors such as the operator’s experience, wedge sealing temperature, sealing speed, and extruder temperature. The effects on the response variables were analyzed, which included overheating, resistance, and leaks. The study identified significant influences of the operator and the temperature of the wedge sealer in warm weather conditions, while the operator’s influence remained prominent in resistance and leakage tests in cold weather. Data transformation techniques, including the arcsine transformation, were employed to ensure statistical validity. Optimal input variable combinations were identified to maximize resistance and minimize overheating and air leaks. The research emphasizes the importance of optimizing the thermofusion process for biodigester construction, highlighting the role of arcsine transformation in improving statistical analysis. The findings enable practitioners to make informed decisions, leading to improvements in welding processes and overall biodigester quality.

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“…Risk assessment through the Ishikawa diagram, heat maps, and FMEA remain widely used tools to assess risk in the pharmaceutical industry. [7][8][9][10]20 Several precedented literature examples illustrate this approach to identify the key material attributes (KMAs) and key process parameters (KPPs) for the reaction stages. These identified KMAs and KPPs are later studied using the DoE trials to gain in-depth insights into the impact of changes in factors (KMAs and KPPS) on the desired responses.…”

Section: ■ Introductionmentioning

confidence: 99%

“…The International Council for Harmonization (ICH) Q9 defines the risk assessment and the approaches that can be used for design irrespective of what stage the product is and should be integrated with ICH Q8 with ICH Q10. Risk assessment through the Ishikawa diagram, heat maps, and FMEA remain widely used tools to assess risk in the pharmaceutical industry. − , Several precedented literature examples illustrate this approach to identify the key material attributes (KMAs) and key process parameters (KPPs) for the reaction stages. These identified KMAs and KPPs are later studied using the DoE trials to gain in-depth insights into the impact of changes in factors (KMAs and KPPS) on the desired responses.…”

Section: Introductionmentioning

confidence: 99%

“…This work focuses on QbD as a systematic risk-based approach to Olaparib 1 (API) development, manufacturing, and lifecycle management. Each of the three chemical transformations was separately studied by employing QbD principles and optimized using the design of experiments (DOE) − to achieve maximum reaction conversion, excellent chemical purity, and isolated yield.…”

Section: Introductionmentioning

confidence: 99%

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Olaparib Process Development Employing Quality by Design (QbD) Principles

Manda,

Komati,

Munaswamy Nariyam

et al. 2024

ACS Omega

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This study focuses on multivariate experimental design and statistical analysis to optimize the process of Olaparib 1. Quality by design (QbD) methodology was adopted for optimization of the Olaparib process consisting of three reaction steps: (1) amidation, (2) deprotection, and (3) acylation. Every chemical conversion was studied in isolation, employing risk assessment to identify key material attributes and key process parameters that may have the potential to impact the reaction. Thereafter, the screening design of experiment (DoE) was employed to scrutinize the factors that significantly impacted yield. Moving forward, the scrutinized factors which were found to impact the responses, the set of critical material attributes (CMAs) and critical process parameters (CPPs), were considered for optimization by applying I-Optimal design to define design space arriving at a robust setting wherein the predefined targets were supposedly optimal. To our delight, we got 95, 91, and 75% yield with more than 99% purity in amidation, deprotection, and acetylation, respectively, which enabled us to systematically identify design space to meet the desired quality target of the product consistently. More importantly, to distinguish the CMAs and CPPs, these elements ought to be monitored to have control of the quality parameter throughout the active pharmaceutical ingredient (API) value chain until commercial manufacturing followed by marketing. Eventually, we have developed a greener process in comparison to precedented one for Olaparib 1.

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Process Development and Optimization of Linagliptin Aided by the Design of Experiments (DoE)

Cited by 5 publications

References 12 publications

Efficient Process Development of Abiraterone Acetate by Employing Design of Experiments

Efficient Process Development of Abiraterone Acetate by Employing Design of Experiments

Optimization of Welding Process of Geomembranes in Biodigesters Using Design of Factorial Experiments

Olaparib Process Development Employing Quality by Design (QbD) Principles

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