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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