Molecular Disorder of Bicalutamide—Amorphous Solid Dispersions Obtained by Solvent Methods
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Solvent Evaporation
2.3. Spray Drying
2.4. Scanning Electron Microscopy (SEM)
2.5. Differential Scanning Calorimetry (DSC)
2.6. Powder X-ray Diffraction (PXRD)
2.7. Laser Diffraction Measurements
2.8. Infrared Spectroscopy (FTIR)
2.9. Dissolution Study
2.10. Intrinsic Dissolution Rate Study
2.11. Solubility Study
2.12. Statistical Analysis
3. Results and Discussion
3.1. Molecular Arrangement
3.1.1. X-ray Powder Diffraction Studies
3.1.2. DSC Studies
3.1.3. Infrared Spectroscopy
3.2. Particle Size and Morphology
3.2.1. Morphology of Particles from Scanning Electron Microscopy
3.2.2. Particle Size Distribution from Laser Diffraction Measurements
3.3. Dissolution Study
3.4. Saturation Solubility
3.5. Intrinsic Dissolution Study
3.6. Statistical Analysis
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Process | Sample | Tg (K) | Tc (K) | Tm (K) |
---|---|---|---|---|
Spray drying | BCL–PVP 1:1 (SD) | 375 | - | - |
BCL–PVP 2:1 (SD) | 357 | 416 | 444; 446 | |
Evaporation | BCL–PVP 1:1 (E) | 376 | - | - |
BCL–PVP 2:1 (E) | 357 | 396 | 449 |
Process | Sample | Dv 10 (µm) | Dv 50 (µm) | Dv 90 (µm) |
---|---|---|---|---|
Spray drying | BCL–PVP 1:1 (SD) | 3.6 | 16.4 | 34.9 |
BCL–PVP 2:1 (SD) | 4.6 | 17.1 | 60.1 | |
BCL (SD) | 5.3 | 15.0 | 38.5 | |
Evaporation | BCL–PVP 1:1 (E) | 80.0 | 352.0 | 1087.0 |
BCL–PVP 2:1 (E) | 54.1 | 252.0 | 672.0 | |
BCL (E) | 14.5 | 55.1 | 251.0 |
Process | Sample | IDR (mg/cm2/min) |
---|---|---|
- | Raw BCL | 0.0144 |
Spray drying | BCL-PVP 1:1 (SD) | 0.0796 |
BCL-PVP 2:1 (SD) | 0.0411 | |
BCL (SD) | 0.0204 | |
Evaporation | BCL-PVP 1:1 (E) | 0.0992 |
BCL-PVP 2:1 (E) | 0.0523 | |
BCL (E) | 0.0131 |
Function | Equation |
---|---|
First-order | |
Korsmeyer–Peppas | |
Hixson–Crowell |
Formulation | MDT (min) | DE (%) | Mathematical Model | ||
---|---|---|---|---|---|
Zero Order | Korsmeyer–Peppas | Hixson–Crowell | |||
(Constant Release) | (Diffusion Based Release) | (Erosion Based Release) | |||
Raw BCL (not processed) | 19.55 | 5.58 | k = 0.1037 Q0 = 2.4571 r2 = 0.9594 p = 0.0035 | k = 1.0895 n = 0.5002 r2 = 0.9981 p < 0.0001 | k = 0.0117 Q0 = 2.66 r2 = 0.9036 p = 0.0114 |
BCL (E) | 20.65 | 22.39 | k = 0.4455 Q0 = 8.9816 r2 = 0.9686 p = 0.0024 * | k = 3.8641 n = 0.5362 r2 = 0.9991 p < 0.0001 * | k = 0.0199 Q0 = 10.02 r2 = 0.9131 p = 0.0096 * |
BCL (SD) | 15.99 | 53.05 | k = 0.8489 Q0 = 27.25 r2 = 0.9040 p = 0.0130 | k = 12.2261 n = 0.4501 r2 = 0.9827 p = 0.0011 * | k = 0.0216 Q0 = 28.13 r2 = 0.8440 p = 0.0263 |
BCL-PVP 1:1 (SD) | 6.28 | 70.30 | k = 0.4905 Q0 = 55.90 r2 = 0.5796 p = 0.1350 | k = 35.4591 n = 0.2164 r2 = 0.8413 p = 0.0358 | k = 0.0104 Q0 = 55.06 r2 = 0.5611 p = 0.1540 |
BCL-PVP 2:1 (SD) | 3.60 | 83.93 | k = 0.1530 Q0 = 82.11 r2 = 0.5043 p = 0.1790 | k = 73.9170 n = 0.0512 r2 = 0.7916 p = 0.0464 | k = 0.0027 Q0 = 82.02 r2 = 0.5014 p = 0.1840 |
BCL-PVP 1:1 (E) | 7.65 | 73.17 | k = 0.5099 Q0 = 58.37 r2 = 0.4847 p = 0.1920 | k = 35.4333 n = 0.2287 r2 = 0.7469 p = 0.0769 | k = 0.0107 Q0 = 56.933 r2 = 0.4759 p = 0.2100 |
BCL-PVP 2:1 (E) | 5.19 | 79.11 | k = 0.2097 Q0 = 75.53 r2 = 0.8494 p = 0.0260 | k = 67.22 n = 0.0632 r2 = 0.9917 p = 0.0003 * | k = 0.0037 Q0 = 75.55 r2 = 0.8394 p = 0.0284 |
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Szafraniec, J.; Antosik, A.; Knapik-Kowalczuk, J.; Gawlak, K.; Kurek, M.; Szlęk, J.; Jamróz, W.; Paluch, M.; Jachowicz, R. Molecular Disorder of Bicalutamide—Amorphous Solid Dispersions Obtained by Solvent Methods. Pharmaceutics 2018, 10, 194. https://doi.org/10.3390/pharmaceutics10040194
Szafraniec J, Antosik A, Knapik-Kowalczuk J, Gawlak K, Kurek M, Szlęk J, Jamróz W, Paluch M, Jachowicz R. Molecular Disorder of Bicalutamide—Amorphous Solid Dispersions Obtained by Solvent Methods. Pharmaceutics. 2018; 10(4):194. https://doi.org/10.3390/pharmaceutics10040194
Chicago/Turabian StyleSzafraniec, Joanna, Agata Antosik, Justyna Knapik-Kowalczuk, Karolina Gawlak, Mateusz Kurek, Jakub Szlęk, Witold Jamróz, Marian Paluch, and Renata Jachowicz. 2018. "Molecular Disorder of Bicalutamide—Amorphous Solid Dispersions Obtained by Solvent Methods" Pharmaceutics 10, no. 4: 194. https://doi.org/10.3390/pharmaceutics10040194
APA StyleSzafraniec, J., Antosik, A., Knapik-Kowalczuk, J., Gawlak, K., Kurek, M., Szlęk, J., Jamróz, W., Paluch, M., & Jachowicz, R. (2018). Molecular Disorder of Bicalutamide—Amorphous Solid Dispersions Obtained by Solvent Methods. Pharmaceutics, 10(4), 194. https://doi.org/10.3390/pharmaceutics10040194