viscosity screening for protein therapeutics
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dV1
d
Shear stress, t
𝛾 =𝑉1
𝑑𝜂 =
𝜏
𝛾
F
F
— What is Viscosity?
— Viscosity Fingerprint
Concentration Effect
pH Effect
Buffer Type
Excipient Type
Temperature
Denaturants
Others
Viscosity screening:
Injectability
Molecular Size in Formulation
Stability in Formulation
—Drug Development
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Small Sample Volume
High-Throughput
Structure
High-Shear
Precision
— Viscometer/Rheometer-on-a-Chip
— Viscometer/Rheometer-on-a-Chip
𝜏 ~ Δ𝑃
𝛾 ~ 𝑄𝜂 =
𝜏
𝛾
— Viscometers
— New Product Release!
— Smallest sample Volume
μ
— Dynamic Range
μ
— Dynamic Range
μ
0.01 1 100 10000 1000000Shear Rate [1/s]
— Injectability
frictionpistonR
LRF w
n
nb )
2(
2
Gauge Dn Db Ln Injection Rate, Q n Shear Rate Viscosity Force Difference %
mm mm mm ml/s 1/s N
29 0.184 6.35 12.7 0.1 1 163,511 30.00 42 0
29 0.184 6.35 12.7 0.1 0.8 173,730 14.03 21 50
29 0.184 6.35 12.7 0.1 0.5 204,389 9.53 17 60
𝜂 = 𝜂∞ +(𝜂0 − 𝜂∞)
1 + (𝜏 𝛾)1−𝑛
— Non-Newtonian Therapeutics
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What is Intrinsic Viscosity?
How does viscosity relate to molecular interaction? 𝜂 = lim
𝐶→0
𝜂𝑠𝑝𝐶
𝜂𝑠𝑝 = 𝜂𝑟 − 1 and
𝜂𝑟 = 𝜂/𝜂𝑠
η
C
𝜂 = 𝐾𝑀𝑤𝑎
𝑟ℎ =3𝑀𝑤[𝜂]
10 𝜋 𝑁𝐴
1/3
𝑟ℎ
Complementary to DLS
*Brandrup 2001. Polymer Handbook
— Intrinsic Viscosity
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•
•
•
𝑟ℎ = 1.3 𝑛𝑚
*Lee et al. Analytical Chemistry 2005
— Molecular Weight and Size
—Concentration
μ
— Denaturation
𝛾 = 1480 1/𝑠
— Stability & Excipients
𝛾 = 1480 1/𝑠
— Denaturants
K. Kawahara and C. Tanford. J. Biological Chemistry, 1966
— Protein Therapeutics
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