Comprehensive Study of Intermediate and Critical Quality Attributes for Process Control of High-Shear Wet Granulation Using Multivariate Analysis and the Quality by Design Approach
A robust manufacturing process and the relationship between intermediate quality attributes (IQAs), critical quality attributes (CQAs), and critical process parameters (CPPs) for high-shear wet granulation was determined in this study. Based on quality by the design (QbD) approach, IQAs, CQAs, and C...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-06-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/11/6/252 |
| _version_ | 1798035329864695808 |
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| author | Jong Kwon Han Beom Soo Shin Du Hyung Choi |
| author_facet | Jong Kwon Han Beom Soo Shin Du Hyung Choi |
| author_sort | Jong Kwon Han |
| collection | DOAJ |
| description | A robust manufacturing process and the relationship between intermediate quality attributes (IQAs), critical quality attributes (CQAs), and critical process parameters (CPPs) for high-shear wet granulation was determined in this study. Based on quality by the design (QbD) approach, IQAs, CQAs, and CPPs of a telmisartan tablet prepared by high-shear wet granulation were determined and then analyzed with multivariate analysis (MVA) to evaluate mutual interactions between IQAs, CQAs, and CPPs. The effects of the CPPs on the IQAs and CQAs were quantitatively predicted with empirical models of best fit. The models were used to define operating space, and an evaluation of the risk of uncertainty in model prediction was performed using Monte Carlo simulation. MVA showed that granule size and granule hardness were significantly related to % dissolution. In addition, granule FE (Flow Energy) and Carr’s index had effects on tablet tensile strength. Using the manufacture of a clinical batch and robustness testing, a scale-up from lab to pilot scale was performed using geometric similarity, agitator torque profile, and agitator tip speed. The absolute biases and relative bias percentages of the IQAs and CQAs generated by the lab and pilot scale process exhibited small differences. Therefore, the results suggest that a risk reduction in the manufacturing process can be obtained with integrated process parameters as a result of the QbD approach, and the relationship between IQAs, CQAs, and CPPs can be used to predict CQAs for a control strategy and SUPAC (Scale-Up and Post-Approval Guidance). |
| first_indexed | 2024-04-11T20:56:43Z |
| format | Article |
| id | doaj.art-a253be8bcc5e4974a49c693321444121 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-11T20:56:43Z |
| publishDate | 2019-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-a253be8bcc5e4974a49c6933214441212022-12-22T04:03:39ZengMDPI AGPharmaceutics1999-49232019-06-0111625210.3390/pharmaceutics11060252pharmaceutics11060252Comprehensive Study of Intermediate and Critical Quality Attributes for Process Control of High-Shear Wet Granulation Using Multivariate Analysis and the Quality by Design ApproachJong Kwon Han0Beom Soo Shin1Du Hyung Choi2School of Pharmacy, Sungkyunkwan University, Suwon 440-746, KoreaSchool of Pharmacy, Sungkyunkwan University, Suwon 440-746, KoreaDepartment of Pharmaceutical Engineering, Inje University, Gyeongnam 621-749, KoreaA robust manufacturing process and the relationship between intermediate quality attributes (IQAs), critical quality attributes (CQAs), and critical process parameters (CPPs) for high-shear wet granulation was determined in this study. Based on quality by the design (QbD) approach, IQAs, CQAs, and CPPs of a telmisartan tablet prepared by high-shear wet granulation were determined and then analyzed with multivariate analysis (MVA) to evaluate mutual interactions between IQAs, CQAs, and CPPs. The effects of the CPPs on the IQAs and CQAs were quantitatively predicted with empirical models of best fit. The models were used to define operating space, and an evaluation of the risk of uncertainty in model prediction was performed using Monte Carlo simulation. MVA showed that granule size and granule hardness were significantly related to % dissolution. In addition, granule FE (Flow Energy) and Carr’s index had effects on tablet tensile strength. Using the manufacture of a clinical batch and robustness testing, a scale-up from lab to pilot scale was performed using geometric similarity, agitator torque profile, and agitator tip speed. The absolute biases and relative bias percentages of the IQAs and CQAs generated by the lab and pilot scale process exhibited small differences. Therefore, the results suggest that a risk reduction in the manufacturing process can be obtained with integrated process parameters as a result of the QbD approach, and the relationship between IQAs, CQAs, and CPPs can be used to predict CQAs for a control strategy and SUPAC (Scale-Up and Post-Approval Guidance).https://www.mdpi.com/1999-4923/11/6/252quality by designscale-up strategycritical process parametersintermediate quality attributeshigh-shear wet granulationmultivariate analysis |
| spellingShingle | Jong Kwon Han Beom Soo Shin Du Hyung Choi Comprehensive Study of Intermediate and Critical Quality Attributes for Process Control of High-Shear Wet Granulation Using Multivariate Analysis and the Quality by Design Approach Pharmaceutics quality by design scale-up strategy critical process parameters intermediate quality attributes high-shear wet granulation multivariate analysis |
| title | Comprehensive Study of Intermediate and Critical Quality Attributes for Process Control of High-Shear Wet Granulation Using Multivariate Analysis and the Quality by Design Approach |
| title_full | Comprehensive Study of Intermediate and Critical Quality Attributes for Process Control of High-Shear Wet Granulation Using Multivariate Analysis and the Quality by Design Approach |
| title_fullStr | Comprehensive Study of Intermediate and Critical Quality Attributes for Process Control of High-Shear Wet Granulation Using Multivariate Analysis and the Quality by Design Approach |
| title_full_unstemmed | Comprehensive Study of Intermediate and Critical Quality Attributes for Process Control of High-Shear Wet Granulation Using Multivariate Analysis and the Quality by Design Approach |
| title_short | Comprehensive Study of Intermediate and Critical Quality Attributes for Process Control of High-Shear Wet Granulation Using Multivariate Analysis and the Quality by Design Approach |
| title_sort | comprehensive study of intermediate and critical quality attributes for process control of high shear wet granulation using multivariate analysis and the quality by design approach |
| topic | quality by design scale-up strategy critical process parameters intermediate quality attributes high-shear wet granulation multivariate analysis |
| url | https://www.mdpi.com/1999-4923/11/6/252 |
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