Screening of formulation parameters for stabilizing recombinant human serum albumin (rHSA) in liquid formulations

TY - JOUR

T1 - Screening of formulation parameters for stabilizing recombinant human serum albumin (rHSA) in liquid formulations

AU - Baldursdottir, Stefania

AU - Tauhaybeche, Mariam

AU - Pekka Pajander, Jari

AU - Bukrinski, Jens T.

AU - Jorgensen, Lene

PY - 2016/8/1

Y1 - 2016/8/1

N2 - In the present study, the stabilizing effect of excipients present in recombinant Human Serum Albumin (rHSA) solutions are studied using rheological analysis. The study was conducted using Design of Experiment (DoE) principles and multivariate analysis approach. It is observed that the excipients octanoate and polysorbate 80 used in the Recombumin Alpha® formulation both increase the stability of the protein reflected by an observed decrease in the complex viscosity interpreted as a decreasing degree of self-association. Octanoate seems to be efficient in protecting the protein at higher temperatures, whereas polysorbate protects against self-association at lower temperatures. Additionally, a synergistic effect of octanoate and polysorbate 80 was observed in a non-linear fashion. This effect would be difficult to assess in a study using univariate analysis of these complex formulations, however the multivariate approach using DoE and Principal Component Analysis (PCA) efficiently illustrated its usefulness in the current study.

AB - In the present study, the stabilizing effect of excipients present in recombinant Human Serum Albumin (rHSA) solutions are studied using rheological analysis. The study was conducted using Design of Experiment (DoE) principles and multivariate analysis approach. It is observed that the excipients octanoate and polysorbate 80 used in the Recombumin Alpha® formulation both increase the stability of the protein reflected by an observed decrease in the complex viscosity interpreted as a decreasing degree of self-association. Octanoate seems to be efficient in protecting the protein at higher temperatures, whereas polysorbate protects against self-association at lower temperatures. Additionally, a synergistic effect of octanoate and polysorbate 80 was observed in a non-linear fashion. This effect would be difficult to assess in a study using univariate analysis of these complex formulations, however the multivariate approach using DoE and Principal Component Analysis (PCA) efficiently illustrated its usefulness in the current study.

KW - Recombumin Alpha (R)

KW - Albumin

KW - Recombinant HSA

KW - Design of experiments

KW - DoE

KW - Rheology

KW - Complex viscosity

KW - Protein formulation

KW - Protein stability

KW - Octanoate

KW - Polysorbate

U2 - 10.1016/j.jddst.2016.05.001

DO - 10.1016/j.jddst.2016.05.001

M3 - Journal article

SN - 1773-2247

VL - 34

SP - 1

EP - 9

JO - Journal of Drug Delivery Science and Technology

JF - Journal of Drug Delivery Science and Technology

ER -