viscosity screening for protein therapeutics

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Page 1: Viscosity Screening for Protein Therapeutics

2

1

• Market leader in Biotechnology Industry

• Headquartered in Silicon Valley

• Patented technology VROC®

• Fortune 500 client base

Page 3: Viscosity Screening for Protein Therapeutics
Page 4: Viscosity Screening for Protein Therapeutics
Page 5: Viscosity Screening for Protein Therapeutics

5

dV1

d

Shear stress, t

𝛾 =𝑉1

𝑑𝜂 =

𝜏

𝛾

F

F

— What is Viscosity?

Page 6: Viscosity Screening for Protein Therapeutics

— Viscosity Fingerprint

Concentration Effect

pH Effect

Buffer Type

Excipient Type

Temperature

Denaturants

Others

Viscosity screening:

Injectability

Molecular Size in Formulation

Stability in Formulation

Page 7: Viscosity Screening for Protein Therapeutics

—Drug Development

7

Small Sample Volume

High-Throughput

Structure

High-Shear

Precision

Page 8: Viscosity Screening for Protein Therapeutics

— Viscometer/Rheometer-on-a-Chip

Page 9: Viscosity Screening for Protein Therapeutics

— Viscometer/Rheometer-on-a-Chip

𝜏 ~ Δ𝑃

𝛾 ~ 𝑄𝜂 =

𝜏

𝛾

Page 10: Viscosity Screening for Protein Therapeutics

— Viscometers

Page 11: Viscosity Screening for Protein Therapeutics

— New Product Release!

Page 12: Viscosity Screening for Protein Therapeutics

— Smallest sample Volume

μ

Page 13: Viscosity Screening for Protein Therapeutics

— Dynamic Range

μ

Page 14: Viscosity Screening for Protein Therapeutics

— Dynamic Range

μ

0.01 1 100 10000 1000000Shear Rate [1/s]

Page 15: Viscosity Screening for Protein Therapeutics
Page 16: Viscosity Screening for Protein Therapeutics

— Injectability

Page 17: Viscosity Screening for Protein Therapeutics

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

Page 18: Viscosity Screening for Protein Therapeutics

18

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

Page 19: Viscosity Screening for Protein Therapeutics

𝜂 = 𝐾𝑀𝑤𝑎

𝑟ℎ =3𝑀𝑤[𝜂]

10 𝜋 𝑁𝐴

1/3

𝑟ℎ

Complementary to DLS

*Brandrup 2001. Polymer Handbook

— Intrinsic Viscosity

Page 20: Viscosity Screening for Protein Therapeutics

𝑟ℎ = 1.3 𝑛𝑚

*Lee et al. Analytical Chemistry 2005

— Molecular Weight and Size

Page 21: Viscosity Screening for Protein Therapeutics

—Concentration

μ

Page 22: Viscosity Screening for Protein Therapeutics

— Denaturation

𝛾 = 1480 1/𝑠

Page 23: Viscosity Screening for Protein Therapeutics

— Stability & Excipients

𝛾 = 1480 1/𝑠

Page 24: Viscosity Screening for Protein Therapeutics

— Denaturants

K. Kawahara and C. Tanford. J. Biological Chemistry, 1966

Page 25: Viscosity Screening for Protein Therapeutics

— Protein Therapeutics

Page 26: Viscosity Screening for Protein Therapeutics
Page 28: Viscosity Screening for Protein Therapeutics