Table 4.
Relaxation times (τ in hours) of freeze-dried formulations evaluated with the TAM and ΔTg methods at 40 °C (n ≥ 3). KWW and MSE derivative expression were used to obtain the relaxation parameters from the TAM data, and Equation 1 was used to calculate for the relaxation parameters from the ΔTg method (a β value of 0.4 was used for the calculation). The standard error is given for all structural relaxation times obtained by KWW, MSE and ΔTg method. Note that the relaxation parameters (τ and τD (hr), β, τβ, τDβ, ln (τβ)KWW, ln (τDβ)MSE and ln (τβ)ΔTg) reported here represents the arithmetic mean of a number of independent experimental values. However, note that the mean of independent τβ or τDβ values, as tabulated, are not exactly the same as the corresponding parameters calculated from the mean values of β and τ or β and τD. The tabulated τβ or τDβ values should be used when making comparisons as these values are more accurate.
| Formulations | KWW |
MSE |
ΔTg |
||||||
|---|---|---|---|---|---|---|---|---|---|
| τ (hr) | β | τ β | ln (τβ) ± SD | τD (hr) | β | τ D β | ln (τDβ) ± SD | ln (τβ) ± SD; β = 0.4 | |
| (A) HES + disaccharide | |||||||||
| HES 5% | 3.4 E+14 | 0.05 | 5.8 | 1.6 ± 0.6 | 1.1 E+09 | 0.19 | 45.3 | 3.8 ± <0.1 | 6.7 ± 0.4 |
| HES 4% + trehalose 1% | 1.2 E+08 | 0.07 | 4.1 | 0.9 ± 0.9 | 1.3 E+08 | 0.20 | 26.2 | 3.3 ± 0.1 | 3.8 ± 0.4 |
| HES 2.5% + trehalose 2.5% | 1.9 E+07 | 0.08 | 4.2 | 1.1 ± 0.9 | 2.3 E+07 | 0.20 | 23.5 | 3.2 ± 0.1 | 2.6 ± 0.2 |
| HES 1% + trehalose 4% | 1.5 E+06 | 0.07 | 3.1 | 0.8 ± 0.8 | 4.5 E+07 | 0.19 | 21.3 | 3.1 ± 0.1 | 3.8 ± 0.7 |
| Trehalose 5% | 6.6 E+06 | 0.07 | 3.0 | 0.4 ± 0.9 | 6.0 E+07 | 0.19 | 21.3 | 3.1 ± 0.1 | 5.1 ± 0.4 |
| HES 4% + sucrose 1% | 4.5 E+02 | 0.04 | 0.9 | -0.2 ± 0.4 | 1.6 E+09 | 0.17 | 22.8 | 3.1 ± <0.1 | 3.3 ± 0.3 |
| HES 2.5% + sucrose 2.5% | 2.2 E+01 | 0.10 | 1.2 | 0.1 ± 0.3 | 5.1 E+05 | 0.18 | 9.7 | 2.3 ± 0.2 | 1.7 ± 0.1 |
| HES 1% + sucrose 4% | 8.4 E+01 | 0.16 | 1.7 | 0.3 ± 0.6 | 2.3 E+04 | 0.19 | 6.7 | 1.9 ± 0.1 | 1.2 ± 0.2 |
| Sucrose 5% | 2.0 E+01 | 0.19 | 1.5 | 0.3 ± 0.4 | 2.7 E+03 | 0.21 | 5.0 | 1.6 ± 0.2 | 1.5 ± 0.2 |
| (B) HES + sorbitol or glycerol | |||||||||
| HES 5% | 5.0 E+06 | 0.26 | 63.1 | 4.1 ± 0.1 | 9.9 E+06 | 0.29 | 94.3 | 4.5 ± 0.1 | 7.3 ± 0.9 |
| + sorbitol 0.5% | 6.8 E+06 | 0.24 | 42.4 | 3.7 ± 0.2 | 7.6 E+07 | 0.24 | 58.2 | 4.1 ± 0.1 | 4.3 ± 0.6 |
| + sorbitol 1% | - | - | - | - | - | - | - | - | - |
| + glycerol 0.5% | 3.1 E+08 | 0.15 | 14.5 | 2.6 ± 0.5 | 7.3 E+07 | 0.20 | 34.4 | 3.5 ± 0.1 | 3.3 ± 0.7 |
| + glycerol 1% | 1.1 E+08 | 0.11 | 9.6 | 2.2 ± 0.3 | 6.3 E+08 | 0.17 | 30.1 | 3.4 ± 0.1 | 1.6 ± 0.9 |
| (C) HES + trehalose 1% + sorbitol or glycerol | |||||||||
| HES 5% + trehalose 1% | 2.9 E+07 | 0.22 | 44.9 | 3.8 ± 0.1 | 3.6 E+08 | 0.23 | 66.0 | 4.2 ± 0.1 | 4.3 ± 1.1 |
| + sorbitol 0.5% | 6.4 E+05 | 0.27 | 35.6 | 3.6 ± 0.1 | 9.7 E+06 | 0.23 | 40.4 | 3.7 ± <0.1 | 2.8 ± 0.3 |
| + sorbitol 1% | - | - | - | - | - | - | - | - | - |
| + glycerol 0.5% | 1.5 E+06 | 0.21 | 18.7 | 2.9 ± 0.2 | 1.2 E+07 | 0.22 | 29.6 | 3.4 ± 0.1 | 2.3 ± 1.1 |
| + glycerol 1% | - | - | - | - | - | - | - | - | - |
| (D) HES + trehalose 3% + sorbitol or glycerol | |||||||||
| HES 5% + trehalose 3% | 1.3 E+06 | 0.28 | 48.3 | 3.9 ± <0.1 | 3.4 E+07 | 0.23 | 52.3 | 4.0 ± 0.1 | 3.0 ± 0.7 |
| + sorbitol 0.5% | 2.6 E+05 | 0.29 | 37.9 | 3.6 ± 0.1 | 3.6 E+06 | 0.26 | 42.6 | 3.7 ± 0.1 | 2.1 ± 0.5 |
| + sorbitol 1% | 3.3 E+04 | 0.34 | 30.9 | 3.4 ± 0.2 | 3.6 E+05 | 0.28 | 29.5 | 3.4 ± 0.1 | 1.2 ± 0.3 |
| + glycerol 0.5% | 1.3 E+05 | 0.27 | 22.0 | 3.1 ± 0.1 | 2.0 E+10 | 0.20 | 22.7 | 3.1 ± 0.3 | 1.4 ± 0.2 |
| + glycerol 1% | 5.2 E+03 | 0.25 | 8.4 | 2.1 ± 0.1 | 8.5 E+04 | 0.21 | 10.8 | 2.4 ± <0.1 | 0.3 ± 0.1 |
| (E) HES 0.75% + trehalose:glycerol | |||||||||
| HES 0.75% + trehalose 3% | 1.3 E+07 | 0.24 | 39.4 | 3.6 ± 0.4 | 5.4 E+08 | 0.19 | 43.2 | 3.8 ± 0.1 | 3.9 ± 0.2 |
| + trehalose 2.91%; glycerol 0.09% | 1.4 E+05 | 0.31 | 37.1 | 3.6 ± 0.1 | 2.3 E+07 | 0.22 | 32.5 | 3.5 ± 0.1 | 2.8 ± 0.2 |
| + trehalose 2.85%; glycerol 0.15% | 1.0 E+05 | 0.31 | 32.6 | 3.5 ± 0.2 | 1.3 E+12 | 0.17 | 23.1 | 3.1 ± 0.3 | 1.9 ± 0.5 |
| + trehalose 2.70%; glycerol 0.30% | 5.7 E+03 | 0.32 | 16.6 | 2.7 ± 0.5 | 3.6 E+05 | 0.21 | 13.1 | 2.5 ± 0.3 | 0.8 ± 0.2 |
| + trehalose 2.55%; glycerol 0.45% | 5.1 E+02 | 0.39 | 11.0 | 2.4 ± 0.1 | 4.5 E+03 | 0.28 | 8.1 | 2.1 ± 0.2 | –0.2 ± 0.2 |