Can pharmaceutical process development become high tech?

McKenzie, Paul; Kiang, San; Tom, Jean W.; Rubin, Aviel D.; Futran, Mauricio

doi:10.1002/aic.11022

Cited by 91 publications

(87 citation statements)

References 14 publications

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“…Despite the challenges faced by the industry, pharmaceutical manufacturing processes remain relatively inefficient and poorly understood as compared with other those in other chemical process industries [4]. This can be attributed in part to the unique challenges associated with pharmaceutical process design.…”

Section: Open Accessmentioning

confidence: 99%

“…Meanwhile regulatory agencies worldwide, including the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), have begun to adopt the quality by design (QbD) paradigm introduced by the ICH Q8 guidance on pharmaceutical development. QbD requires that companies demonstrate understanding of the way in which variability in raw materials as well as process design and operating conditions affect product quality and use this understanding to implement effective quality control strategies [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Open Accessmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

2013

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“…1,2 Traditionally, the batch mode of operation dominates the pharmaceutical industry. A shift from the batch mode of operation to the continuous mode, where raw materials are converted to the drug products in an integrated facility, offers opportunities to improve the overall flexibility, reliability, and efficiency of the production process.…”

Section: Introductionmentioning

confidence: 99%

Nonlinear Model-Based Control of Thin-Film Drying for Continuous Pharmaceutical Manufacturing

Mesbah

Versypt

Zhu

et al. 2013

Ind. Eng. Chem. Res.

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This paper considers the model-based control of composition and thickness for a thin-film drying process used in the continuous manufacturing of pharmaceutical tablets. In this nonlinear distributed dynamical system, a drug formulation solution is coated onto a moving surface and then dried to form thin films of approximately 250 μm in thickness. A dynamic optimizer is designed that employs a first-principles process model to simulate the spatial distribution of solvent concentration in the film and the thin film shrinkage during drying. A critical parameter to describe the highly nonlinear dynamics of the thin-film drying is the mutual polymer−solvent diffusion coefficient, which strongly depends on solvent concentration and film temperature. Two optimal control problems are studied for set point tracking of solvent concentration and minimization of energy consumption in the dryer while satisfying various operational and product quality constraints. An unscented Kalman filter is designed to facilitate the output feedback implementation of the dynamic optimizer and to estimate unmeasured thin-film quality attributes such as the film thickness. The performance of the model-based controller is compared to that of a proportional integral controller in two simulation case studies. The nonlinear model-based control strategy has improved versatility and the potential to reduce production of off spec material.

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“…Although the pharmaceutical industries must satisfy strict production speci�cation norms imposed by regulatory authorities, mainly due to inefficient control strategies [1,2] and the nonpredictive effects of input parameters, the �nal products obtained are oen nonuniform with a high level of variability with respect to product quality [3]. Moreover, the behavior of powder processing units are not well characterized as compared to the �uid processing units due to the absence of set of governing equations derived from the �rst principles which can describe granular �ow under speci�c conditions.…”

Section: Introductionmentioning

confidence: 99%

Mathematical Development and Comparison of a Hybrid PBM-DEM Description of a Continuous Powder Mixing Process

Sen

Dubey

Singh

et al. 2013

Journal of Powder Technology

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is paper describes the development of a multidimensional population balance model (PBM) which can account for the dynamics of a continuous powder mixing/blending process. e PBM can incorporate the important design and process conditions and determine their effects on the various critical quality attributes (CQAs) accordingly. e important parameters considered in this study are blender dimensions and presence of noise in the inlet streams. e blender dynamics have been captured in terms of composition of the ingredients, (relative standard deviation) RSD, and (residence time distribution) RTD. PBM interacts with discrete element modeling (DEM) via one-way coupling which forms a basic framework for hybrid modeling. e results thus obtained have been compared against a full DEM simulation which is a more fundamental particle-level model that elucidates the dynamics of the mixing process. Results show good qualitative agreement which lends credence to the use of coupled PBM as an effective tool in control and optimization of mixing process due to its relatively fewer computational requirements compared to DEM.

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Can pharmaceutical process development become high tech?

Cited by 91 publications

References 14 publications

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

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

Nonlinear Model-Based Control of Thin-Film Drying for Continuous Pharmaceutical Manufacturing

Mathematical Development and Comparison of a Hybrid PBM-DEM Description of a Continuous Powder Mixing Process

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