Molecular Mobility and Stability Studies of Amorphous Imatinib Mesylate
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Preparation of Amorphous Sample
2.3. Physical Stability Studies
2.4. Differential Scanning Calorimetry (DSC)
2.5. Thermogravimetric Analysis (TGA)
2.6. Powder X-ray Diffraction Analysis (XRPD)
2.7. Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy (ATR-FTIR)
2.8. Scanning Electron Microscopy (SEM)
3. Results and Discussion
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Time | Tp [oC] | TOnset [oC] | TEndset [oC] | ΔHf [J g−1] | Tg [°C] | ΔCp [J g−1] |
---|---|---|---|---|---|---|
0 day | 218.7 | 212.4 | 224.5 | 10.73 | 100.9 | 0.168 |
2 weeks | 218.9 | 212.3 | 224.5 | 11.42 | 101.0 | 0.238 |
1 month | 218.8 | 212.1 | 224.8 | 10.52 | 99.0 | 0.140 |
3 months | 218.5 | 212.0 | 224.4 | 11.37 | 100.0 | 0.208 |
6 months | 219.1 | 213.8 | 222.6 | 10.70 | 105.2 | 0.301 |
15 months | 218.3 | 211.9 | 224.3 | 11.76 | 106.4 | 0.302 |
T [°C] | Maximum Enthalpy ∆H∞ [J∙g−1] | Estimated Parameters | R-Value | t50% [h] | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Mean molecular Relaxation Time Constant τ [s] | Relaxation Time Distribution Parameter β | ||||||||||
Estimate τ | Standard Error SE | Confidence Interval −95% CI/+95% CI | P-Value | Estimate β | Standard Error SE | Confidence Interval −95% CI/+95% CI | P-Value | ||||
3 | 43.4 | 3.6 × 1039 | 2.8 × 1035 | 2.80 × 1035/ 1.72 × 1036 | 0.0161 | 0.0689 | 0.000267 | 0.0682/ 0.0697 | 1.29 × 10−9 | 0.998 | 4.92 × 1033 |
15 | 38.3 | 2.95 ×∙1028 | 8.62 × 1023 | 5.99 × 1024/ 1.04 × 1025 | 0.000216 | 0.098 | 0.000206 | 0.0979/ 0.099 | 1.15 × 10−10 | 0.999 | 1.98 × 1023 |
25 | 34.1 | 4.13 ×∙1022 | 2.04 × 1018 | 6.23 × 1018/ 1.67 × 1019 | 0.00245 | 0.122 | 0.000570 | 0.121/ 0.124 | 2.84 × 10−9 | 0.997 | 5.73 × 1017 |
30 | 32.0 | 6.39 ×∙1021 | 3.93 × 1017 | 7.66 × 1017/ 2.79 × 1018 | 0.006289 | 0.119 | 0.000724 | 0.117/ 0.121 | 8.17 × 10−9 | 0.997 | 8.22 × 1016 |
T [°C] | Time [h] | Observed Value | Predicted Value | Residual | Standard Error | Confidence Interval | Residual Sum of Squares RRS | Shapiro Wilk W/p | |
---|---|---|---|---|---|---|---|---|---|
−95% CIi | +95% CIi | ||||||||
3 °C | 0.1 | 0.130 | 0.122 | 0.00791 | 0.0027 | 0.115 | 0.130 | 0.0002599 | W = 0.9426/ p = 0.6808 |
1.0 | 0.132 | 0.143 | −0.01145 | 0.0031 | 0.134 | 0.152 | |||
2.0 | 0.151 | 0.150 | 0.00056 | 0.0033 | 0.141 | 0.159 | |||
4.0 | 0.152 | 0.157 | −0.00527 | 0.0034 | 0.148 | 0.167 | |||
8.0 | 0.170 | 0.165 | 0.00535 | 0.0035 | 0.155 | 0.175 | |||
16.0 | 0.176 | 0.173 | 0.00309 | 0.0037 | 0.163 | 0.183 | |||
15 °C | 0.1 | 0.105 | 0.108 | −0.00315 | 0.0013 | 0.104 | 0.111 | 0.0000712 | W = 0.8655/ p = 0.20908 |
1.0 | 0.139 | 0.135 | 0.00349 | 0.0016 | 0.131 | 0.140 | |||
2.0 | 0.142 | 0.145 | −0.00254 | 0.0017 | 0.140 | 0.149 | |||
4.0 | 0.160 | 0.155 | 0.00557 | 0.0018 | 0.150 | 0.160 | |||
8.0 | 0.166 | 0.166 | −0.00014 | 0.0018 | 0.161 | 0.171 | |||
16.0 | 0.174 | 0.177 | −0.00341 | 0.0020 | 0.172 | 0.183 | |||
25 °C | 0.1 | 0.112 | 0.120 | −0.00821 | 0.0032 | 0.111 | 0.129 | 0.0004607 | W = 0.9089/ p = 0.42970 |
1.0 | 0.155 | 0.159 | −0.00383 | 0.0040 | 0.148 | 0.170 | |||
2.0 | 0.183 | 0.173 | 0.0101 | 0.0042 | 0.161 | 0.185 | |||
4.0 | 0.197 | 0.188 | 0.00890 | 0.0046 | 0.176 | 0.201 | |||
8.0 | 0.210 | 0.205 | 0.00531 | 0.0049 | 0.191 | 0.218 | |||
16.0 | 0.210 | 0.223 | −0.0131 | 0.0052 | 0.208 | 0.237 | |||
30 °C | 0.1 | 0.181 | 0.162 | 0.0188 | 0.0052 | 0.147 | 0.176 | 0.0012054 | W = 0.9593/ p = 0.81450 |
1.0 | 0.189 | 0.212 | −0.0234 | 0.0065 | 0.195 | 0.231 | |||
2.0 | 0.227 | 0.231 | −0.00406 | 0.0069 | 0.212 | 0.250 | |||
4.0 | 0.243 | 0.251 | −0.00738 | 0.0074 | 0.230 | 0.271 | |||
8.0 | 0.287 | 0.272 | 0.0151 | 0.0078 | 0.250 | 0.294 | |||
16.0 | 0.298 | 0.296 | 0.00206 | 0.0084 | 0.272 | 0.319 |
Time | Tm [oC] | Rate of Mass Loss [% min−1] | TOnset [oC] | TEndset [oC] | Res [%] | T0.5 wt.% [oC] | T1.0 wt.% [oC] | Moisture Content [%] |
---|---|---|---|---|---|---|---|---|
0 day | 373.9 | 5.72 | 326.2 | 419.6 | 39.71 | 271.5 | 287.6 | - |
2 weeks | 373.6 | 5.44 | 327.7 | 419.4 | 42.37 | 269.3 | 287.2 | - |
1 month | 379.7 | 5.36 | 327.8 | 419.3 | 42.48 | 275.5 | 291.5 | 1.16 |
3 months | 373.9 | 5.58 | 326.3 | 419.8 | 38.92 | 275.7 | 289.5 | 2.51 |
6 months | 365.7 | 5.05 | 322.6 | 411.9 | 43.75 | 274.6 | 280.3 | 2.54 |
15 months | 362.6 | 5.35 | 319.9 | 410.4 | 41.55 | 278.4 | 288.1 | 3.95 |
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Karolewicz, B.; Górniak, A.; Marciniak, D.M.; Mucha, I. Molecular Mobility and Stability Studies of Amorphous Imatinib Mesylate. Pharmaceutics 2019, 11, 304. https://doi.org/10.3390/pharmaceutics11070304
Karolewicz B, Górniak A, Marciniak DM, Mucha I. Molecular Mobility and Stability Studies of Amorphous Imatinib Mesylate. Pharmaceutics. 2019; 11(7):304. https://doi.org/10.3390/pharmaceutics11070304
Chicago/Turabian StyleKarolewicz, Bożena, Agata Górniak, Dominik M. Marciniak, and Igor Mucha. 2019. "Molecular Mobility and Stability Studies of Amorphous Imatinib Mesylate" Pharmaceutics 11, no. 7: 304. https://doi.org/10.3390/pharmaceutics11070304
APA StyleKarolewicz, B., Górniak, A., Marciniak, D. M., & Mucha, I. (2019). Molecular Mobility and Stability Studies of Amorphous Imatinib Mesylate. Pharmaceutics, 11(7), 304. https://doi.org/10.3390/pharmaceutics11070304