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Table 4 Summary of degradation rate constants and activation energies determined using the three stability methods

From: Non-isothermal stability by linear heating: a fast method for preformulation stability screening of drugs at the discovery and development interface

Compound #

LNISOa Method (1 week)

Conventional Isothermal

(8 weeks)

Abbreviated Isothermal

(4 weeks)

11 time points

6 time points

Ea (kcal/mol)

k25 (1/day)

Ea (kcal/mol)

k25 (1/day)

Ea (kcal/mol)

k25 (1/day)

Ea (kcal/mol)

k25 (1/day)

A1b

Stable, no degradation observed.

A2b

Stable, no degradation observed.

A3

Unstable

A4

24.22

6.58E-4

24.25

6.49E-4

25.14

4.76E-4

24.66

5.42E-4

A5b

Stable, no degradation observed.

A6b

Stable, no degradation observed.

A7

27.68

3.78E-4

27.80

3.70E-4

28.18

2.88E-4

28.49

2.67E-4

A8

25.47

1.32E-5

25.62

1.26E-5

24.45

1.67E-5

23.14

2.15E-5

A9

Precipitations, data could not be processed.

A10b

Stable, no degradation observed.

A11 c

14.14

4.14E-4

12.69

6.39E-4

18.71

6.67E-5

15.58

1.61E-4

A12

17.54

3.02E-3

17.72

2.86E-3

18.66

1.63E-3

16.85

2.04E-3

A13

25.26

2.76E-4

25.20

2.80E-4

24.93

2.31E-4

24.54

2.51E-4

A14

31.78

4.33E-5

31.70

4.40E-5

32.98

2.60E-5

32.81

2.70E-5

A15

31.91

1.80E-5

31.87

1.82E-5

31.68

1.40E-5

30.35

1.90E-5

A16 c

9.59

3.94E-4

10.36

3.27E-4

10.32

8.40E-5

12.11

8.50E-5

A17

27.05

3.09E-6

26.91

3.20E-6

25.57

2.94E-6

28.64

1.82E-6

A18

Precipitations, data could not be processed.

  1. a LNISO Non-isothermal by Linear Heating
  2. bFive compounds (A1, A2, A5, A6 and A10) with no significant degradations, considered ‘stable’
  3. cTwo compounds (A11 and A16), which didn’t follow the first order degradation kinetics