Sucrose and Trehalose in Therapeutic Protein Formulations

Singh, Satish K.

doi:10.1007/978-3-319-90603-4_3

Cited by 17 publications

(7 citation statements)

References 116 publications

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“…52,81 This crystallization behavior of trehalose might be due to the lower solubility, hygroscopicity, and ability to form clusters at higher concentrations compared to other saccharides like sucrose. 82 Despite the complex crystallization process and transformation between different crystal forms, the dihydrate crystal reported in the study above returns to the amorphous form instead of transforming into the anhydrous crystal. 82 Whether the subsequent amorphization of trehalose from the dehydrate crystal can restore phase homogeneity and protein interaction is questionable.…”

Section: Crystallization Of Componentsmentioning

confidence: 87%

“…82 Despite the complex crystallization process and transformation between different crystal forms, the dihydrate crystal reported in the study above returns to the amorphous form instead of transforming into the anhydrous crystal. 82 Whether the subsequent amorphization of trehalose from the dehydrate crystal can restore phase homogeneity and protein interaction is questionable. 82 Currently, it is unknown to what extent this crystallization event occurs with other excipients and its consequence.…”

Section: Crystallization Of Componentsmentioning

confidence: 87%

“…82 Whether the subsequent amorphization of trehalose from the dehydrate crystal can restore phase homogeneity and protein interaction is questionable. 82 Currently, it is unknown to what extent this crystallization event occurs with other excipients and its consequence. Fortunately, only extended annealing time (3 h or more) appears to give rise to trehalose crystallization.…”

Section: Crystallization Of Componentsmentioning

confidence: 99%

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Inhomogeneous Distribution of Components in Solid Protein Pharmaceuticals: Origins, Consequences, Analysis, and Resolutions

Nguyen¹,

Frijlink²,

Hinrichs³

2020

Journal of Pharmaceutical Sciences

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Successful development of stable solid protein formulations usually requires the addition of one or several excipients to achieve optimal stability. In these products, there is a potential risk of an inhomogeneous distribution of the various ingredients, specifically the ratio of protein and stabilizer may vary. Such inhomogeneity can be detrimental for stability but is mostly neglected in literature. In the past, it was challenging to analyze inhomogeneous component distribution, but recent advances in analytical techniques have revealed new options to investigate this phenomenon. This paper aims to review fundamental aspects of the inhomogeneous distribution of components of freeze-dried and spray-dried protein formulations. Four key topics will be presented and discussed, including the sources of component inhomogeneity, its consequences on protein stability, the analytical methods to reveal component inhomogeneity, and possible solutions to prevent or mitigate inhomogeneity.

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Section: Crystallization Of Componentsmentioning

confidence: 87%

Section: Crystallization Of Componentsmentioning

confidence: 87%

Section: Crystallization Of Componentsmentioning

confidence: 99%

See 1 more Smart Citation

Inhomogeneous Distribution of Components in Solid Protein Pharmaceuticals: Origins, Consequences, Analysis, and Resolutions

Nguyen¹,

Frijlink²,

Hinrichs³

2020

Journal of Pharmaceutical Sciences

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“…Sugars or polyols are often part of biopharmaceutical formulations as stabilizing agent for liquid and solid formulations [449][450][451][452]. The most common sugar or polyol molecules utilized in formulations are sucrose, trehalose, sorbitol, and mannitol [453], which are also known to act as radical scavengers and antioxidant [454][455][456].…”

Section: Photo-oxidation Of Excipientsmentioning

confidence: 99%

Photo-Oxidation of Therapeutic Protein Formulations: From Radical Formation to Analytical Techniques

et al. 2021

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UV and ambient light-induced modifications and related degradation of therapeutic proteins are observed during manufacturing and storage. Therefore, to ensure product quality, protein formulations need to be analyzed with respect to photo-degradation processes and eventually protected from light exposure. This task usually demands the application and combination of various analytical methods. This review addresses analytical aspects of investigating photo-oxidation products and related mediators such as reactive oxygen species generated via UV and ambient light with well-established and novel techniques.

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“…For example, sucrose can undergo recrystallization 9 or hydrolysis if the matrix is sufficiently acidic. 10 In general, low residual moisture is favored for lyophilized protein products. 11 On the other hand, it has been reported that overdrying may result in increased insoluble aggregate content and decreased protein activity in some protein formulations.…”

Section: ■ Introductionmentioning

confidence: 99%

Photolytic Labeling To Quantify Peptide–Water Interactions in Lyophilized Solids

Chen

Topp

2019

Mol. Pharmaceutics

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Interactions of a lyophilized peptide with water and excipients in a solid matrix were explored using photolytic labeling. A model peptide “KLQ” (Ac–QELHKLQ–NHCH3) was covalently labeled with NHS–diazirine (succinimidyl 4,4′-azipentanoate), and the labeled peptide (KLQ–SDA) was formulated and exposed to UV light in both solution and lyophilized solids. Solid samples contained the following excipients at a 1:400 molar ratio: sucrose, trehalose, mannitol, histidine, or arginine. Prior to UV exposure, the lyophilized solids were exposed to various relative humidity (RH) environments (8, 13, 33, 45, and 78%), and the resulting solid moisture content (Karl Fischer titration) and glass transition temperature (T g; differential scanning calorimetry, DSC) were measured. To initiate photolytic labeling, solution and solid samples were exposed to UV light at 365 nm for 30 min. Photolytic-labeling products were quantified using reversed-phase high-performance liquid chromatography (rp-HPLC) and mass spectrometry (MS). In lyophilized solids, studies excluding oxygen and using H2 18O confirmed that the source of oxygen in KLQ adducts with a mass increase of 18 amu are attributable to reaction with water, while those with a mass increase of 16 amu are not attributable to reaction with either water or molecular oxygen. In solids containing sucrose or trehalose, peptide–excipient adducts decreased with increasing solid moisture content, while peptide–water adducts increased only at lower RH exposure and then plateaued, in partial agreement with the water replacement hypothesis.

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Sucrose and Trehalose in Therapeutic Protein Formulations

Cited by 17 publications

References 116 publications

Inhomogeneous Distribution of Components in Solid Protein Pharmaceuticals: Origins, Consequences, Analysis, and Resolutions

Inhomogeneous Distribution of Components in Solid Protein Pharmaceuticals: Origins, Consequences, Analysis, and Resolutions

Photo-Oxidation of Therapeutic Protein Formulations: From Radical Formation to Analytical Techniques

Photolytic Labeling To Quantify Peptide–Water Interactions in Lyophilized Solids

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