Template-Assisted Crystallization Behavior in Stirred Solutions of the Monoclonal Antibody Anti-CD20: Probability Distributions of Induction Times

Gerard, Charline J. J.; Briuglia, Maria L.; Rajoub, Nazer; Mastropietro, Teresa F.; Chen, Wenqian; Heng, Jerry Y. Y.; Profio, Gianluca Di; Horst, Joop H. ter

doi:10.1021/acs.cgd.1c01324

Cited by 6 publications

(4 citation statements)

References 47 publications

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“…Similar results were obtained by Shah et al [36] when different-molecular-weight proteins were crystallised using the templates with engineering pores with an optimum size similar to their hydrodynamic radius. Further, an antibody named anti-CD20 was crystallised using the specifically designed porous silica template with a pore size in the range of the molecular diameter of the antibody [37,38]. Silica with a 10 nm pore size also influenced the diglycine induction time; 6 nm and 10 nm pores are significantly not different, and hence are also able to crystallise diglycine and reduce the induction time.…”

Section: Resultsmentioning

confidence: 99%

Experimental Elucidation of Templated Crystallization and Secondary Processing of Peptides

et al. 2023

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The crystallization of peptides offers a sustainable and inexpensive alternative to the purification process. In this study, diglycine was crystallised in porous silica, showing the porous templates’ positive yet discriminating effect. The diglycine induction time was reduced by five-fold and three-fold upon crystallising in the presence of silica with pore sizes of 6 nm and 10 nm, respectively. The diglycine induction time had a direct relationship with the silica pore size. The stable form (α-form) of diglycine was crystallised in the presence of porous silica, with the diglycine crystals obtained associated with the silica particles. Further, we studied the mechanical properties of diglycine tablets for their tabletability, compactability, and compressibility. The mechanical properties of the diglycine tablets were similar to those of pure MCC, even with the presence of diglycine crystals in the tablets. The diffusion studies of the tablets using the dialysis membrane presented an extended release of diglycine through the dialysis membrane, confirming that the peptide crystal can be used for oral formulation. Hence, the crystallization of peptides preserved their mechanical and pharmacological properties. More data on different peptides can help us produce oral formulation peptides faster than usual.

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Section: Resultsmentioning

confidence: 99%

Experimental Elucidation of Templated Crystallization and Secondary Processing of Peptides

et al. 2023

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“…Subsequently, this methodology has been extensively adopted by various researchers for a diverse range of studies in nucleation kinetics. These applications include laser-induced crystallization, template-assisted crystallization, , ultrasound-assisted crystallization, examining the influence of impurities on nucleation processes , and determining vital parameters such as the critical size of nuclei, activation energy, and growth rates. , …”

Section: Introductionmentioning

confidence: 99%

“…18 Subsequently, this methodology has been extensively adopted by various researchers for a diverse range of studies in nucleation kinetics. These applications include laser-induced crystallization, 19 template-assisted crystallization, 20,21 ultrasound-assisted crystallization, 22 examining the influence of impurities on nucleation processes 23,24 and determining vital parameters such as the critical size of nuclei, activation energy, and growth rates. 25,26 Nucleation occurs when supersaturation is formed in the particular solvent; hence solvent properties play a significant role in analyzing the nucleation rate via solute−solvent intermolecular interaction.…”

Section: ■ Introductionmentioning

confidence: 99%

Nucleation Kinetics of Ascorbic Acid in Various Aqueous Solvents

Yadav,

Kendall,

Dumitrescu

et al. 2024

Ind. Eng. Chem. Res.

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The nucleation kinetics of ascorbic acid in water and binary solvent systems of ethanol−water and isopropanol−water have been analyzed by the classical nucleation theory. For that, in total, 3065 data of induction time were collected by the isothermal method at five supersaturations in each solvent system. The induction time data are well represented with the Poisson probability distribution to determine the nucleation rate (J) and growth time (t g ). The nucleation rate is found to be highest in water (1319.87 m −3 s −1 ) and decreases with increasing the alcohol composition in the binary solvent systems, showing the minimum nucleation rate (179.24 m −3 s −1 ) in the isopropanol−water system with a 0.6/0.4 mole fraction ratio. Furthermore, the kinetic parameter (A) decreases, whereas the thermodynamic parameter (B) increases with an increase in the alcohol composition in the aqueous solvent system. The interfacial energy (γ), critical radius (r c ), and Gibbs free energy (ΔG c ) were observed to be high for solvent systems with higher alcohol composition, which indicates a lower interaction between the solute and solution due to high interfacial tension.

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“…Their large structure and flexibility ultimately translate into difficulties in crystallizing from solution and poor processability of the crystallites once they are produced. Recent advances in technologies and in knowledge on mAb crystallization have however led to a shift in mindset, and several batch-crystallizations of mAbs have recently been reported. ,− …”

Section: Introductionmentioning

confidence: 99%

Small-Angle X-ray Scattering as a Powerful Tool for Phase and Crystallinity Assessment of Monoclonal Antibody Crystallites in Support of Batch Crystallization

Larpent,

Codan,

Bothe

et al. 2024

Mol. Pharmaceutics

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Crystalline suspensions of monoclonal antibodies (mAbs) have great potential to improve drug substance isolation and purification on a large scale and to be used for drug delivery via high-concentration formulations. Crystalline mAb suspensions are expected to have enhanced chemical and physical properties relative to mAb solutions delivered intravenously, making them attractive candidates for subcutaneous delivery. In contrast to small molecules, the development of protein crystalline suspensions is not a widely used approach in the pharmaceutical industry. This is mainly due to the challenges in finding crystalline hits and the suboptimal physical properties of the resulting crystallites when hits are found. Modern advances in instrumentation and increased knowledge of mAb crystallization have, however, resulted in higher probabilities of discovering crystal forms and improving their particle properties and characterization. In this regard, physical, analytical characterization plays a central role in the initial steps of understanding and later optimizing the crystallization of mAbs and requires careful selection of the appropriate tools. This contribution describes a novel crystal structure of the antibody pembrolizumab and demonstrates the usefulness of small-angle X-ray scattering (SAXS) for characterizing its crystalline suspensions. It illustrates the advantages of SAXS when used to (i) confirm crystallinity and crystal phase of crystallites produced in batch mode; (ii) confirm crystallinity under various conditions and detect variations in crystal phases, enabling fine-tuning of the crystallizations for phase control across multiple batches; (iii) monitor the physical response and stability of the crystallites in suspension with regard to filtration and washing; and (iv) monitor the physical stability of the crystallites upon drying. Overall, this work highlights how SAXS is an essential tool for mAb crystallization characterization.

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Template-Assisted Crystallization Behavior in Stirred Solutions of the Monoclonal Antibody Anti-CD20: Probability Distributions of Induction Times

Cited by 6 publications

References 47 publications

Experimental Elucidation of Templated Crystallization and Secondary Processing of Peptides

Experimental Elucidation of Templated Crystallization and Secondary Processing of Peptides

Nucleation Kinetics of Ascorbic Acid in Various Aqueous Solvents

Small-Angle X-ray Scattering as a Powerful Tool for Phase and Crystallinity Assessment of Monoclonal Antibody Crystallites in Support of Batch Crystallization

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