Current Trends in API Co-Processing: Spherical Crystallization and Co-Precipitation Techniques

Dhondale, Madhukiran R.; Nambiar, Amritha G.; Singh, Maan; Mali, Abhishek R; Agrawal, Ashish Kumar; Shastri, Nalini R.; Kumar, Pradeep; Kumar, Dinesh

doi:10.1016/j.xphs.2023.02.005

Cited by 13 publications

(7 citation statements)

References 105 publications

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“…Therefore, more pragmatic solutions are required for precisely controlling the particle properties instead of increasing seed load to 10%, as required here. To this end, nucleation platforms for the in situ preparation of considerably fine seeds have been developed. − In addition, crystal engineering strategies such as coprecipitation have been proposed for selecting solid materials exhibiting isotropic crystal growths. ,, An immediate CMC strategy would be to resort to a different DP technology with less demanding requirements, in terms of particle properties. This would allow relaxing the particle constraints, set in the GSA, and as a consequence expand the design space toward a less demanding region of seeding conditions.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…Antisolvent crystallization offers superior control over size, morphology and polymorphism of the final crystal, as well as lower energy consumption in supersaturation control [35]. However, scaling up an antisolvent crystallization process is very difficult [36][37][38], as the crystal size depends on the mixing conditions and whether the antisolvent is uniformly incorporated into the solution; hence, several mixing devices have been developed such as T-mixer, confined impinging jet, static mixer, and multi-inlet vortex mixer, to name a few [39][40][41].…”

Section: Antisolvent Crystallization Of Pharmaceuticalsmentioning

confidence: 99%

Recent Progress in Antisolvent Crystallization of Pharmaceuticals with a Focus on the Membrane‐Based Technologies

Haghighizadeh,

Mahdavi,

Rajabi

2024

Chem Eng & Technol

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Continuous crystallization of pharmaceuticals has been in the center of attention during the past two decades, with a more focus on the large‐scale production of active pharmaceutical ingredients. The increasing demand for pharmaceuticals requires high‐throughput production of drug crystals with different solubilities, stabilities, shapes, habits, polymorphs, and size distributions. With numerous advantages including low cost, ease of scale‐up, and superior control over polymorph and size distribution of drug crystals, antisolvent crystallization is one of the most promising crystallization methods recently attempted. However, it fails to deliver the required characteristic where the crystal systems tend to grow and for the preparation of metastable polymorphs. This review focuses on the most recent efforts to tackle these drawbacks by coupling antisolvent crystallization with cooling, supercritical‐assisted, microfluidics‐assisted, and membrane‐assisted crystallization. This systematic review aims to provide a concise summary of each coupled antisolvent technique and their positive and negative aspects. This review can be used as a guideline for pharmacist, biologists, and chemists, who are interested in the crystal engineering of pharmaceuticals to pave the way for further developments in this field.

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“…Direct compression (DC) eliminates the intermediary production steps involved in conventional tableting, including the costly granulation and drying procedures, significantly reducing production costs and time. , In order to obtain direct compressible drug particles, spherical crystallization (SC) was proposed by Kawashima et al and first applied to salicylic acid . SC can produce drug particles with spherical shape, and it is regarded as an efficient particle design technique which is capable of combining crystallization, milling, and granulation into a single crystallization unit operation. , It stands out as an efficient method to simultaneously improve flowability and tabletability when compared to the common granulation whereby “loss of tabletability” has been commonly noticed. − After the proposal of SC by Kawashima et al, different SC techniques are developed and applied to various drugs, such as benzoic acid, − celecoxib, , and ibuprofen, − to enhance their particle properties. For example, using spherical crystallization, a DC tablet formulation containing up to 99% APIs could be prepared …”

Section: Introductionmentioning

confidence: 99%

“…5 SC can produce drug particles with spherical shape, and it is regarded as an efficient particle design technique which is capable of combining crystallization, milling, and granulation into a single crystallization unit operation. 6,7 It stands out as an efficient method to simultaneously improve flowability and tabletability when compared to the common granulation whereby "loss of tabletability" has been commonly noticed. 8−10 After the proposal of SC by Kawashima et al, different SC techniques are developed and applied to various drugs, such as benzoic acid, 11−13 celecoxib, 14,15 and ibuprofen, 16−18 to enhance their particle properties.…”

Section: Introductionmentioning

confidence: 99%

Particle Design of Drugs via Spherical Crystallization: A Review from Fundamental Aspects to Technology Development

Sun,

Bi,

Zhao

et al. 2024

Crystal Growth & Design

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In the pharmaceutical industry, the production process of most active pharmaceutical ingredients involves at least one crystallization step. Design of drug spheres via various spherical crystallization technologies can impart crystals with certain superior attributes including high flowability and compressibility as well as excellent mechanical properties. Some new spherical crystallization approaches and design principles have been proposed in recent years. This review aims to review the up-to-date design principles and preparation technologies of drug spheres, providing a guide for design, preparation, and performance evaluation of the drug spheres. Herein, we review the mechanisms and design principles of the spherical crystallization first, and subsequently various technologies reported in the literature are reviewed with the critical process parameters being analyzed. Lastly, the challenges facing the development of spherical crystallization for drugs are discussed.

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Current Trends in API Co-Processing: Spherical Crystallization and Co-Precipitation Techniques

Cited by 13 publications

References 105 publications

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

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

Recent Progress in Antisolvent Crystallization of Pharmaceuticals with a Focus on the Membrane‐Based Technologies

Particle Design of Drugs via Spherical Crystallization: A Review from Fundamental Aspects to Technology Development

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