Improving the Manufacturability of Cohesive and Poorly Compactable API for Direct Compression of Mini-tablets at High Drug Loading via Particle Engineering

Chen, Liang; Lin, Yiqing; Irdam, Erwin; Madden, Nicole; Osei-Yeboah, Frederick

doi:10.1007/s11095-022-03413-9

Cited by 3 publications

(2 citation statements)

References 34 publications

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“…Chen et al compared two different approaches to API milling and reinforced the importance of particle-scale properties, such as the particle size, particle size distribution (PSD), and particle morphology [15]. They considered an important topic of improving the manufacturability of cohesive and poorly compactable API for direct compression of mini-tablets at high drug loading.…”

Section: Processing and Process Understandingmentioning

confidence: 99%

Crystal and Particle Engineering – An Indispensable Tool for Developing and Manufacturing Quality Pharmaceutical Products

Sun

Davé

2022

Pharm Res

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Design and manufacture of high-quality pharmaceutical products remains challenging due to the inherent complexities arising, in part, from multitudes of components in particulate forms, each having different functionality and potential for unwanted interactions during processing, storage, handling, or administration. Hence, it follows that particles and crystals play an essential role in pharmaceutical manufacturing. Successful manufacturing and quality of finished pharmaceutical products, even if the final dosage form may not be a solid, critically depend on powder properties, such as flowability, tabletability, wettability, and solubility. These powder properties, in turn, are controlled by the properties of constituting particles or crystals of active pharmaceutical ingredients (API) and excipients, such as size, size distribution, shape, porosity, mechanical properties, surface energy, and surface roughness [1,2]. Hence, appropriate engineering of crystals or particles through various processes, such as crystallization, granulation (dry, wet, fluid bed), hot-melt extrusion, spray-drying, and dry coating, is necessary for the purpose of overcoming problems in pharmaceutical manufacturing. Thus, engineering pharmaceutical materials at particle level is an important step in solving many problems in pharmaceutical manufacturing. In summary, the interrelationships among structure, property, performance, and processing, succinctly captured through materials science tetrahedron (MST) [1], could guide research in

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Section: Processing and Process Understandingmentioning

confidence: 99%

Crystal and Particle Engineering – An Indispensable Tool for Developing and Manufacturing Quality Pharmaceutical Products

Sun

Davé

2022

Pharm Res

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“…At present, the reconciliation of crystallization, which involves dual purification and particle engineering, with downstream drug-product manufacturing has become increasingly important in the biopharmaceutical industry. The increasing business and scientific demands have fueled the continuous manufacturing of dry drug products (DPs). − For the continuous dry manufacturing of DPs, active pharmaceutical ingredients (APIs) with appropriate particle size and morphology are crucial. − The interplay between these characteristics determines, to a considerable extent, the feasibility of dry-DP processes, such as continuous direct compression. − …”

Section: Introductionmentioning

confidence: 99%

Using Morphological Population Balance to Develop a Model-Driven Quality-by-Design Approach for Crystallization Processes

Douieb,

Calado,

Mitchell

et al. 2024

Crystal Growth & Design

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Quality by design-based crystallization of active pharmaceutical ingredient (API) particles with optimal properties for lean drug-product manufacturing remains a long-standing goal of the biopharmaceutical industry; however, its practical application is difficult. Particle and powder properties, such as size, shape, and flowability, along with the key performance indicators of crystallization, such as purity, yield, and robustness, must be considered for the process design. However, considering these parameters for a dynamical system, such as crystallization, is particularly challenging as the involved process conditions and product attributes are strongly interdependent. This challenge is addressed herein by applying morphological population balance (MPB) modeling to the crystallization of an API with a needle-like morphology and poor powder properties, which pose challenges during downstream processing. The potential of seeded batch cooling crystallization is explored for simultaneously improving the particle size and aspect ratio of the API by manipulating seeding conditions, such as seed loading and morphology. Moreover, a novel calibration strategy was developed for the obtained MPB model by performing sequential thermal cycling–wet-milling experiments. The desired kinetic parameters were obtained via these experiments with minimal material consumption and time. The calibrated model was then used to construct probabilistic-design spaces for different seeding conditions and assess the feasibility and reproducibility of the crystallization yields. Results revealed that for persistent needles, relatively small uncertainty in the estimated kinetic parameters cascades to significant shrinkage of the design space. Owing to this feature, batch seeded cooling crystallization is not a suitable platform to control the particle size and morphology of the API of interest; even if the seeding strategy includes high, by industrial standards, seed loadings (5–10%) and low aspect ratio seeds (<2.5). Thus, alternative approaches, such as crystal nucleation control and/or particle engineering, are required to overcome the limitations of APIs having persistent needle-like morphologies. Overall, this study demonstrates a novel paradigm for the calibration and interrogation of the MPB model, which are essential for their industrial application and regulatory compliance.

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Challenges encountered in the transfer of atorvastatin tablet manufacturing - commercial batch-based production as a basis for small-scale continuous tablet manufacturing tests

Lyytikäinen,

Kyllönen,

Ervasti

et al. 2023

International Journal of Pharmaceutics

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Improving the Manufacturability of Cohesive and Poorly Compactable API for Direct Compression of Mini-tablets at High Drug Loading via Particle Engineering

Cited by 3 publications

References 34 publications

Crystal and Particle Engineering – An Indispensable Tool for Developing and Manufacturing Quality Pharmaceutical Products

Crystal and Particle Engineering – An Indispensable Tool for Developing and Manufacturing Quality Pharmaceutical Products

Using Morphological Population Balance to Develop a Model-Driven Quality-by-Design Approach for Crystallization Processes

Challenges encountered in the transfer of atorvastatin tablet manufacturing - commercial batch-based production as a basis for small-scale continuous tablet manufacturing tests

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