Multi-scale pharmaceutical process understanding: From particle to powder to dosage form

Hamad, Mazen L.; Bowman, Keith J.; Smith, Nathan D.; Sheng, Xiaohong; Morris, Kenneth R.

doi:10.1016/j.ces.2010.01.037

Cited by 31 publications

(15 citation statements)

References 25 publications

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“…Once the relationship is clear, material properties can be modified by changing the structure of the matter through process engineering approaches and thereby delivering the desired performance. Understanding the properties and behavior of pharmaceutical materials is critical to the design of a safe and effective dosage form [36]. In the future, product-process modeling and optimization will increasingly contribute to pharmaceutical product-process development [37].…”

Section: Particle Technology Applied To Drug Formulationsmentioning

confidence: 99%

Modeling and Simulation of Process Technology for Nanoparticulate Drug Formulations—A Particle Technology Perspective

Uhlemann

Diedam

Hoheisel³

et al. 2020

Pharmaceutics

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Crystalline organic nanoparticles and their amorphous equivalents (ONP) have the potential to become a next-generation formulation technology for dissolution-rate limited biopharmaceutical classification system (BCS) class IIa molecules if the following requisites are met: (i) a quantitative understanding of the bioavailability enhancement benefit versus established formulation technologies and a reliable track record of successful case studies are available; (ii) efficient experimentation workflows with a minimum amount of active ingredient and a high degree of digitalization via, e.g., automation and computer-based experimentation planning are implemented; (iii) the scalability of the nanoparticle-based oral delivery formulation technology from the lab to manufacturing is ensured. Modeling and simulation approaches informed by the pharmaceutical material science paradigm can help to meet these requisites, especially if the entire value chain from formulation to oral delivery is covered. Any comprehensive digitalization of drug formulation requires combining pharmaceutical materials science with the adequate formulation and process technologies on the one hand and quantitative pharmacokinetics and drug administration dynamics in the human body on the other hand. Models for the technical realization of the drug production and the distribution of the pharmaceutical compound in the human body are coupled via the central objective, namely bioavailability. The underlying challenges can only be addressed by hierarchical approaches for property and process design. The tools for multiscale modeling of the here-considered particle processes (e.g., by coupled computational fluid dynamics, population balance models, Noyes–Whitney dissolution kinetics) and physiologically based absorption modeling are available. Significant advances are being made in enhancing the bioavailability of hydrophobic compounds by applying innovative solutions. As examples, the predictive modeling of anti-solvent precipitation is presented, and options for the model development of comminution processes are discussed.

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Section: Particle Technology Applied To Drug Formulationsmentioning

confidence: 99%

Modeling and Simulation of Process Technology for Nanoparticulate Drug Formulations—A Particle Technology Perspective

Uhlemann

Diedam

Hoheisel³

et al. 2020

Pharmaceutics

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“…The chemical compounds used for medication purposes are becoming more complex and, simultaneously, the demand for highly engineered innovative formulations is growing . As such, the role of materials science is gaining importance . Material characterization will be progressively more significant, as explaining the processability of complex systems requires a detailed characterization of the structure of matter.…”

Section: Fundamental Tools For Increased Process Understandingmentioning

confidence: 99%

“…[182][183][184][185] As such, the role of materials science is gaining importance. [186][187][188] Material characterization will be progressively more significant, as explaining the processability of complex systems requires a detailed characterization of the structure of matter. Development of products based on well-defined solid forms (polymorph, solvate, salt, co-crystal, and amorphous) of a given low-molecular-weight compounds, as well as the complex nature of biopharmaceutical drugs, such as monoclonal antibodies and recombinant proteins, are underpinning the importance of fundamental materials science.…”

Section: Materials Sciencementioning

confidence: 99%

The Future of Pharmaceutical Manufacturing Sciences

Rantanen

Khinast

2015

Journal of Pharmaceutical Sciences

363

152

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The entire pharmaceutical sector is in an urgent need of both innovative technological solutions and fundamental scientific work, enabling the production of highly engineered drug products. Commercial‐scale manufacturing of complex drug delivery systems (DDSs) using the existing technologies is challenging. This review covers important elements of manufacturing sciences, beginning with risk management strategies and design of experiments (DoE) techniques. Experimental techniques should, where possible, be supported by computational approaches. With that regard, state‐of‐art mechanistic process modeling techniques are described in detail. Implementation of materials science tools paves the way to molecular‐based processing of future DDSs. A snapshot of some of the existing tools is presented. Additionally, general engineering principles are discussed covering process measurement and process control solutions. Last part of the review addresses future manufacturing solutions, covering continuous processing and, specifically, hot‐melt processing and printing‐based technologies. Finally, challenges related to implementing these technologies as a part of future health care systems are discussed. © 2015 The Authors. Journal of Pharmaceutical Sciences published by Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3612–3638, 2015

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“…Provided that models are predictive, have been validated with available experimentally measured data and have acceptable accuracy, model-based approaches can be used with advantage to identify and reduce the design space to ensure enhanced product quality and manufacturing efficiency [8]. QbD for pharmaceutical manufacturing is essentially the recognition that the manufacturing process requires the consideration of fundamental modeling coupled with robust control strategies and in-line sensing for effective process control and operation [13]. Furthermore, given the increasing importance of PAT placed by the pharmaceutical industries [14][15][16], real-time process control for an integrated pharmaceutical process is a crucial research area that needs to be addressed.…”

Section: Introduction and Objectivesmentioning

confidence: 99%

Model-Based Control-Loop Performance of a Continuous Direct Compaction Process

et al. 2011

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This study is concerned with enhanced modelbased control of a continuous direct compression pharmaceutical process. The control-loop performance is assessed in silico and results obtained will be incorporated into the pilot plant facility of the continuous direct compaction process at the NSF Engineering Research Center of Rutgers University. The models used in the study are obtained via system identification from a combination of first principlesbased dynamic models, experimental data, and/or literature data. The main objective of the paper is to formulate an effective control strategy at the basic/regulatory level, for the integrated continuous operation of the direct compaction process, and to maintain the process at the desired set-points, taking into account the multivariable process interactions and disturbances. Simulations show that that at very mild interactions, the proposed regulatory control strategy is able to maintain set-points at desired values. However, at moderate to high process interactions, oscillatory behavior of controlled variables is seen. The presence of disturbances also resulted in poor control-loop performance. Results also lend credence to the development of advanced control strategies in such scenarios and will be addressed in future work. Optimal control tuning parameters are obtained from a derivative-free optimization algorithm.

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Multi-scale pharmaceutical process understanding: From particle to powder to dosage form

Cited by 31 publications

References 25 publications

Modeling and Simulation of Process Technology for Nanoparticulate Drug Formulations—A Particle Technology Perspective

Modeling and Simulation of Process Technology for Nanoparticulate Drug Formulations—A Particle Technology Perspective

The Future of Pharmaceutical Manufacturing Sciences

Model-Based Control-Loop Performance of a Continuous Direct Compaction Process

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