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

•

•

•

•

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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