Downstream Processing of Amorphous and Co-Amorphous Olanzapine Powder Blends
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Methods
2.2.1. Preparation of Amorphous and Co-Amorphous Olanzapine
2.2.2. Characterization of Pure Amorphous and Co-Amorphous Olanzapine
2.2.3. Formulation of Tablets
2.2.4. Blending
2.2.5. Tableting
2.2.6. Quantification of the Fraction of Amorphous and Co-Amorphous Olanzapine
2.2.7. Stability Studies
2.2.8. Characterization of Blends and Tablets
2.2.9. Statistical Analysis
3. Results and Discussion
3.1. Assessment of the Amorphization and Co-Amorphization of Olanzapine
3.2. Rheological Characterization of Crystalline, Amorphous, and Co-Amorphous Olanzapine
3.3. Pressure-Induced Amorphization
3.4. Tableting
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Substance | A | B |
---|---|---|
OLZ | 30 | 30 |
SAC | 0 | 18 |
Dibasic calcium phosphate anhydrous | 45 | 27 * |
Microcrystalline cellulose | 20 | 20 |
Polyvinylpyrrolidone | 5 | 5 |
Cohesion Index (mm) | Cake Strength (g) | Angle of Repose (°) | |
---|---|---|---|
OLZ | |||
Crystalline | 14.3 ± 0.6 | 174.7 ± 3.4 | 51.7 ± 0.1 |
Amorphous | 15.8 ± 0.3 * | 181.4 ± 9.9 | 52.8 ± 0.3 * |
OLZ:SAC | |||
Crystalline | 12.7 ± 0.4 | 159.6 ± 6.9 | 51.0 ± 0.9 |
Co-amorphous | 25.2 ± 1.2 ** | 180.7 ± 5.9 * | 54.6 ± 1.7 * |
True Density (g/cm3) | Carr’s Index | |
---|---|---|
OLZ | ||
Crystalline | 1.3053 ± 0.0022 | 39.7 ± 0.5 |
Amorphous | 1.2764 ± 0.0014 ** | 41.3 ± 0.6 * |
OLZ:SAC | ||
Crystalline | 1.3897 ± 0.0017 | 34.0 ± 1.0 |
Co-amorphous | 1.3501 ± 0.0058 ** | 36.7 ± 1.1 * |
Tensile Strength (MPa) | Disintegration Time (s) | Work of Compaction (J) | Ejection Force (kN) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Compaction Pressure (MPa) | 25 | 90 | 155 | 25 | 90 | 155 | 25 | 90 | 155 | 25 | 90 | 155 |
Formulation A | ||||||||||||
Crystalline | 0.12 ± 0.00 | 0.95 ± 0.01 | 1.64 ± 0.04 | 31.0 ± 2.7 | 26.2 ± 3.3 | 64.7 ± 3.1 | 0.184 ± 0.007 | 0.839 ± 0.018 | 1.357 ± 0.011 | 0.014 ± 0.001 | 0.093 ± 0.010 | 0.142 ± 0.014 |
Amorphous | 0.29 ± 0.00 ** | 1.14 ± 0.02 ** | 2.11 ± 0.08 ** | 686.3 ± 63.2 ** | 2470.7 ± 45.0 ** | 7131.0 ± 201.06 ** | 0.212 ± 0.013 * | 0.890 ± 0.028 ** | 1.422 ± 0.018 ** | 0.018 ± 0.002 | 0.089 ± 0.007 | 0.133 ± 0.012 |
Formulation B | ||||||||||||
Crystalline | 0.16 ± 0.01 | 1.01 ± 0.05 | 1.84 ± 0.04 | 56.0 ± 3.6 | 48.7 ± 4.5 | 63.7 ± 5.9 | 0.192 ± 0.005 | 0.902 ± 0.028 | 1.382 ± 0.020 | 0.028 ± 0.004 | 0.163 ± 0.009 | 0.288 ± 0.013 |
Co-amorphous | 0.59 ± 0.01 ** | 1.97 ± 0.01 ** | 2.74 ± 0.05 ** | 167.0 ± 4.2 ** | 420.0 ± 87.2 ** | 1364.5 ± 12.02 ** | 0.250 ± 0.017 * | 1.090 ± 0.034 ** | 1.754 ± 0.025 ** | 0.054 ± 0.014 | 0.234 ± 0.026 * | 0.433 ± 0.041 * |
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da Costa, N.F.; Daniels, R.; Fernandes, A.I.; Pinto, J.F. Downstream Processing of Amorphous and Co-Amorphous Olanzapine Powder Blends. Pharmaceutics 2022, 14, 1535. https://doi.org/10.3390/pharmaceutics14081535
da Costa NF, Daniels R, Fernandes AI, Pinto JF. Downstream Processing of Amorphous and Co-Amorphous Olanzapine Powder Blends. Pharmaceutics. 2022; 14(8):1535. https://doi.org/10.3390/pharmaceutics14081535
Chicago/Turabian Styleda Costa, Nuno F., Rolf Daniels, Ana I. Fernandes, and João F. Pinto. 2022. "Downstream Processing of Amorphous and Co-Amorphous Olanzapine Powder Blends" Pharmaceutics 14, no. 8: 1535. https://doi.org/10.3390/pharmaceutics14081535