Formation of mannitol hemihydrate in freeze-dried protein formulations-A design of experiment approach

Research output: Contribution to journal › Journal article › Research

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Formation of mannitol hemihydrate in freeze-dried protein formulations-A design of experiment approach. / Larsen, Helena Marie Lindholm; Trnka, Hjalte; Grohganz, Holger.

In: International Journal of Pharmaceutics, Vol. 460, No. 1-2, 02.01.2014, p. 45-52.

Research output: Contribution to journal › Journal article › Research

Harvard

Larsen, HML, Trnka, H & Grohganz, H 2014, 'Formation of mannitol hemihydrate in freeze-dried protein formulations-A design of experiment approach', International Journal of Pharmaceutics, vol. 460, no. 1-2, pp. 45-52. https://doi.org/10.1016/j.ijpharm.2013.11.009

APA

Larsen, H. M. L., Trnka, H., & Grohganz, H. (2014). Formation of mannitol hemihydrate in freeze-dried protein formulations-A design of experiment approach. International Journal of Pharmaceutics, 460(1-2), 45-52. https://doi.org/10.1016/j.ijpharm.2013.11.009

Vancouver

Larsen HML, Trnka H, Grohganz H. Formation of mannitol hemihydrate in freeze-dried protein formulations-A design of experiment approach. International Journal of Pharmaceutics. 2014 Jan 2;460(1-2):45-52. https://doi.org/10.1016/j.ijpharm.2013.11.009

Author

Larsen, Helena Marie Lindholm ; Trnka, Hjalte ; Grohganz, Holger. / Formation of mannitol hemihydrate in freeze-dried protein formulations-A design of experiment approach. In: International Journal of Pharmaceutics. 2014 ; Vol. 460, No. 1-2. pp. 45-52.

Bibtex

@article{60604a509fc54ef8b7c3548ae7a1a1cd,

title = "Formation of mannitol hemihydrate in freeze-dried protein formulations-A design of experiment approach",

abstract = "Since the discovery of mannitol hemihydrate, this form of mannitol has been seen as potentially negative with regard to the stability of pharmaceutical formulations. The formation of mannitol hemihydrate is reported in several case studies; however, no systematic investigation has been performed so far. In this study, design of experiments was applied for response surface modelling of mannitol hemihydrate formation. The formulation parameters investigated in a composite face-centred design were the overall solid content, protein concentration, protein type and the ratio between mannitol and sucrose. Additionally, annealing as process parameter was included in a full factorial mixed design. For two proteins, models with a high goodness of fit (R(2): 0.82 and 0.93) and goodness of prediction (Q(2): 0.78 and 0.89) were achieved. Inclusion of the process parameter annealing resulted in models of similar quality. The successful application of design of experiments showed that the most prominent factors enhancing the formation of hemihydrate were a high protein concentration, low relative mannitol content and annealing at -20°C.",

author = "Larsen, {Helena Marie Lindholm} and Hjalte Trnka and Holger Grohganz",

year = "2014",

month = jan,

day = "2",

doi = "10.1016/j.ijpharm.2013.11.009",

language = "English",

volume = "460",

pages = "45--52",

journal = "International Journal of Pharmaceutics",

issn = "0378-5173",

publisher = "Elsevier",

number = "1-2",

}

RIS

TY - JOUR

T1 - Formation of mannitol hemihydrate in freeze-dried protein formulations-A design of experiment approach

AU - Larsen, Helena Marie Lindholm

AU - Trnka, Hjalte

AU - Grohganz, Holger

PY - 2014/1/2

Y1 - 2014/1/2

N2 - Since the discovery of mannitol hemihydrate, this form of mannitol has been seen as potentially negative with regard to the stability of pharmaceutical formulations. The formation of mannitol hemihydrate is reported in several case studies; however, no systematic investigation has been performed so far. In this study, design of experiments was applied for response surface modelling of mannitol hemihydrate formation. The formulation parameters investigated in a composite face-centred design were the overall solid content, protein concentration, protein type and the ratio between mannitol and sucrose. Additionally, annealing as process parameter was included in a full factorial mixed design. For two proteins, models with a high goodness of fit (R(2): 0.82 and 0.93) and goodness of prediction (Q(2): 0.78 and 0.89) were achieved. Inclusion of the process parameter annealing resulted in models of similar quality. The successful application of design of experiments showed that the most prominent factors enhancing the formation of hemihydrate were a high protein concentration, low relative mannitol content and annealing at -20°C.

AB - Since the discovery of mannitol hemihydrate, this form of mannitol has been seen as potentially negative with regard to the stability of pharmaceutical formulations. The formation of mannitol hemihydrate is reported in several case studies; however, no systematic investigation has been performed so far. In this study, design of experiments was applied for response surface modelling of mannitol hemihydrate formation. The formulation parameters investigated in a composite face-centred design were the overall solid content, protein concentration, protein type and the ratio between mannitol and sucrose. Additionally, annealing as process parameter was included in a full factorial mixed design. For two proteins, models with a high goodness of fit (R(2): 0.82 and 0.93) and goodness of prediction (Q(2): 0.78 and 0.89) were achieved. Inclusion of the process parameter annealing resulted in models of similar quality. The successful application of design of experiments showed that the most prominent factors enhancing the formation of hemihydrate were a high protein concentration, low relative mannitol content and annealing at -20°C.

U2 - 10.1016/j.ijpharm.2013.11.009

DO - 10.1016/j.ijpharm.2013.11.009

M3 - Journal article

C2 - 24239581

VL - 460

SP - 45

EP - 52

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

IS - 1-2

ER -

ID: 97643119

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