General procedure to aid the development of continuous pharmaceutical processes using multivariate statistical modeling – An industrial case study

Tomba, Emanuele; Martin, Marialuisa De; Facco, Pierantonio; Robertson, John; Zomer, Simeone; Bezzo, Fabrizio; Barolo, Massimiliano

doi:10.1016/j.ijpharm.2013.01.018

Cited by 24 publications

(18 citation statements)

References 41 publications

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“…The loading bar plots are displayed in Figure 3. The loadings of PLS model indicated which process parameters or granule properties affected product quality and estimated their relative contribution to quality 25,30. The first of the four predictive components in the PLS regression model explained 61.9% of CQAs variations.…”

Section: Resultsmentioning

confidence: 99%

“…Westerhuis and Conengracht23 pioneered the application of multiblock partial least squares (MBPLS)24 to improve the interpretability and understanding of a two-step process, including wet granulation and tableting. Tomba et al25 proposed a procedure for the application of MBPLS to support the development of a continuous pharmaceutical process from earlier stage using an industrial case. Extensive multivariate modeling applications for process understanding and control are described in a number of studies 26–34…”

Section: Introductionmentioning

confidence: 99%

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Statistical modeling methods to analyze the impacts of multiunit process variability on critical quality attributes of Chinese herbal medicine tablets

Sun

Xu²,

Zhang

et al. 2016

DDDT

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The quality of Chinese herbal medicine tablets suffers from batch-to-batch variability due to a lack of manufacturing process understanding. In this paper, the Panax notoginseng saponins (PNS) immediate release tablet was taken as the research subject. By defining the dissolution of five active pharmaceutical ingredients and the tablet tensile strength as critical quality attributes (CQAs), influences of both the manipulated process parameters introduced by an orthogonal experiment design and the intermediate granules’ properties on the CQAs were fully investigated by different chemometric methods, such as the partial least squares, the orthogonal projection to latent structures, and the multiblock partial least squares (MBPLS). By analyzing the loadings plots and variable importance in the projection indexes, the granule particle sizes and the minimal punch tip separation distance in tableting were identified as critical process parameters. Additionally, the MBPLS model suggested that the lubrication time in the final blending was also important in predicting tablet quality attributes. From the calculated block importance in the projection indexes, the tableting unit was confirmed to be the critical process unit of the manufacturing line. The results demonstrated that the combinatorial use of different multivariate modeling methods could help in understanding the complex process relationships as a whole. The output of this study can then be used to define a control strategy to improve the quality of the PNS immediate release tablet.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Statistical modeling methods to analyze the impacts of multiunit process variability on critical quality attributes of Chinese herbal medicine tablets

Sun

Xu²,

Zhang

et al. 2016

DDDT

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“…More recently these methods have also been used to characterize and optimize formulations of solid dose products [144,145,171]. Tomba et al [136][137][138] and Garcia-Munoz et al [172][173][174] explain the use of latent variable methods to enable in silico design of new product formulations. The authors present and validate multivariate optimization methods for raw material selection by optimizing powder properties (i.e., bulk density, flow) of blends using combinations of API and excipient formulations.…”

Section: Product Formulationmentioning

confidence: 99%

Optimization Methodologies for the Production of Pharmaceutical Products

Escotet‐Espinoza

Rogers

Ierapetritou

2016

Methods in Pharmacology and Toxicology

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Finding the most beneficial conditions during the development of a given product or process is among one of the top goals for both scientist and engineers across all industries. In the pharmaceutical industry, as global competition increases and there is a higher demand for accessible quality products, it is important to focus on the improvement of product development and manufacturing. Optimization methodologies can greatly aid the production of pharmaceutical products by providing a systematic framework to process improvement. In this review, general concepts regarding the implementation of optimization methods are introduced along with examples of their application in pharmaceutical manufacturing process design and formulation development. An overview of optimization methodologies used for the improvement of batch and continuous pharmaceutical manufacturing is presented. Challenges in the application of optimization methods in pharmaceutical manufacturing are discussed along with a future outlook of the field and its place in pharmaceutical process and product design. Overall the review points to optimization as a critical component in the design of improved and effective pharmaceutical products, in alignment with the common goals of both regulatory agencies and industry.

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“…However, for relatively small sample sizes the variability in the estimates can be high, resulting in unstable error estimation [232,233]. Cross-validation, particularly as it pertains to multivariate regression and latent variable methods, is discussed extensively in the literature [234,235]. An alternative to cross validation is the bootstrap procedure.…”

Section: Model Validation and Verificationmentioning

confidence: 99%

Modeling of Particulate Processes for the Continuous Manufacture of Solid-Based Pharmaceutical Dosage Forms

2013

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Abstract:The objective of this work is to present a review of computational tools and models for pharmaceutical processes, specifically those for the continuous manufacture of solid dosage forms. Relevant mathematical methods and simulation techniques are discussed, as is the development of process models for solids-handling unit operations. Continuous processing is of particular interest in the current study because it has the potential to improve the efficiency and robustness of pharmaceutical manufacturing processes.

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General procedure to aid the development of continuous pharmaceutical processes using multivariate statistical modeling – An industrial case study

Cited by 24 publications

References 41 publications

Statistical modeling methods to analyze the impacts of multiunit process variability on critical quality attributes of Chinese herbal medicine tablets

Statistical modeling methods to analyze the impacts of multiunit process variability on critical quality attributes of Chinese herbal medicine tablets

Optimization Methodologies for the Production of Pharmaceutical Products

Modeling of Particulate Processes for the Continuous Manufacture of Solid-Based Pharmaceutical Dosage Forms

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