A perspective on PSE in pharmaceutical process development and innovation

Gernaey, Krist V.; Cervera-Padrell, Albert E.; Woodley, John M.

doi:10.1016/j.compchemeng.2012.02.022

Cited by 128 publications

(90 citation statements)

References 148 publications

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“…The Process Analytical Technology (PAT) guidance introduced by the FDA encouraged the monitoring of critical quality and performance attributes during processing, with the goal of ensuring final product quality (4,5). As part of this renewed emphasis on improvement of manufacturing, the pharmaceutical industry has begun to develop more efficient production systems with more intensive use of on-line measurement and sensing, real-time quality control and process control tools which offer the potential for reduced production costs, faster product release, reduced variability, increased flexibility and efficiency, and improved product quality (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Drop-on-Demand System for Manufacturing of Melt-based Solid Oral Dosage: Effect of Critical Process Parameters on Product Quality

et al. 2015

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ABSTRACT. The features of a drop-on-demand-based system developed for the manufacture of meltbased pharmaceuticals have been previously reported. In this paper, a supervisory control system, which is designed to ensure reproducible production of high quality of melt-based solid oral dosages, is presented. This control system enables the production of individual dosage forms with the desired critical quality attributes: amount of active ingredient and drug morphology by monitoring and controlling critical process parameters, such as drop size and product and process temperatures. The effects of these process parameters on the final product quality are investigated, and the properties of the produced dosage forms characterized using various techniques, such as Raman spectroscopy, optical microscopy, and dissolution testing. A crystallization temperature control strategy, including controlled temperature cycles, is presented to tailor the crystallization behavior of drug deposits and to achieve consistent drug morphology. This control strategy can be used to achieve the desired bioavailability of the drug by mitigating variations in the dissolution profiles. The supervisor control strategy enables the application of the drop-on-demand system to the production of individualized dosage required for personalized drug regimens.

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Section: Introductionmentioning

confidence: 99%

Drop-on-Demand System for Manufacturing of Melt-based Solid Oral Dosage: Effect of Critical Process Parameters on Product Quality

et al. 2015

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“…The necessity of a multi-scale approach towards granulation process 15 optimisation, monitoring and control has been documented in detail by Cameron and Wang [19]. 16 Several approaches are adopted for macro-scale modelling of granulation processes as overviewed in ta-17 ble 5. Two main modelling approaches mostly used for HSWG processes are (1) population balance mod-18 elling (PBM); and (2) the discrete element method (DEM).…”

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confidence: 99%

“…Adjustments or tuning in model parameters through 14 calibration are necessary to improve the ability of granulation models to replicate process measured condi- 15 tions and properly reflect the impact of any change in it ( Figure 3). This section of the review comprises the 16 currently reported developments in modelling practices and related measurement tools of the batch HSWG 17 in order to illustrate the degree to which this potential has been exploited thus far. This overview then 18 allows identifying potential gaps and developing a list of unexplored possibilities for facing the challenges 19 ( Table 1) inherent to the continuous form of HSWG.…”

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confidence: 99%

“…Furthermore, ICH published a more recent and extensive guid- 2 It is generally accepted that the availability of mathematical process model(s) and suitable measurement 3 device(s) for a pharmaceutical process when successfully interlinked (i.e. performing proper model calibra-4 tion and validation), can lead to functional and robust knowledge based control of process and product 5 quality [16]. Unfortunately, many of the parameters used in HSWG models are difficult to measure in the 6 field, yet they have a substantial impact on the performance of the granulation models.…”

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confidence: 99%

“…wetting and nucleation), some 7 empirical expressions are included in the model (leading to so-called semi-empirical or "grey box" models) 8 in order to allow simulation of the granulation system. 9 Although the underlying mechanisms of the granulation process are still being investigated, especially in 10 case of TSG where such detailed knowledge is not yet established [3], it is well motivated to model the 11 system at meso-or macro-scale such as to exploit the benefits of process system engineering (PSE) methods 12 and tools [16]. PSE tools rely on domain knowledge and mathematical and experimental techniques to build 13 computer models which relate the change at a molecular level to macro-scale system performance in order 14 to develop and optimise the system.…”

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confidence: 99%

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Model-based analysis of high shear wet granulation from batch to continuous processes in pharmaceutical production – A critical review

Kumar

Gernaey

Beer

et al. 2013

European Journal of Pharmaceutics and Biopharmaceutics

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109

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The manufacturing of pharmaceutical dosage forms, which has traditionally been a batch-wise process, is now also transformed into a series of continuous operations. Some operations such as tabletting and milling are already performed in continuous mode, while the adaptation towards a complete continuous production line is still hampered by complex steps such as granulation and drying which are considered to be too inflexible to handle potential product change-overs. Granulation is necessary in order to achieve good flowability properties and better control of drug content uniformity. This paper reviews modelling and supporting measurement tools for the high shear wet granulation (HSWG) process, which is an important granulation technique due to the inherent benefits and the suitability of this unit operation for the desired switch to continuous mode. For gaining improved insight of the complete system, particle-level mechanisms are required to be better understood, and linked with an appropriate meso-or macro-scale model. A brief review has been provided to understand the mechanisms of the granulation process at micro or particle-level such as those involving wetting and nucleation, aggregation, breakage and consolidation. Further, population balance modelling (PBM) and the discrete element method (DEM), which are the current state-of-the-art methods for granulation modelling at micro-to meso-scale, are discussed. The DEM approach has a major role to play in future research as it bridges the gap between micro-and meso-scales. Furthermore, interesting developments in the measurement technologies are discussed with a focus towards inline measurements of the granulation process to obtain experimental data which are required for developing good models. Based on the current state of the developments, the review focuses on the twin screw granulator as a device for * Email address: ingmar.nopens@ugent.be, Tel.: +32 (0)9 264 61 96; fax: +32 (0) continuous HSWG and attempts to critically evaluate the current process. As a result, a set of open research questions are identified. These questions need to be answered in the future in order to fill the knowledge gap that currently exists both at micro-and macro-scale, and which is currently limiting the further development of the process to its full potential in pharmaceutical applications.

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Process Intensification in the Chemical Industry: A Review

Curcio

2013

Sustainable Development in Chemical Engineering Innovative Technologies

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A perspective on PSE in pharmaceutical process development and innovation

Cited by 128 publications

References 148 publications

Drop-on-Demand System for Manufacturing of Melt-based Solid Oral Dosage: Effect of Critical Process Parameters on Product Quality

Drop-on-Demand System for Manufacturing of Melt-based Solid Oral Dosage: Effect of Critical Process Parameters on Product Quality

Model-based analysis of high shear wet granulation from batch to continuous processes in pharmaceutical production – A critical review

Process Intensification in the Chemical Industry: A Review

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