High-Shear Wet Granulation of SMEDDS Based on Mesoporous Carriers for Improved Carvedilol Solubility
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Methods
2.2.1. Preparation of Liquid SMEDDS Loaded with Carvedilol
2.2.2. Granulation Dispersion Preparation
2.2.3. Determination of Granulation Dispersion Rheological Properties
2.2.4. SMEDDS Solidification by Manual Wet Granulation
2.2.5. SMEDDS Solidification by High-Shear Wet Granulation
2.2.6. Loss on Drying
2.2.7. Granules Size and Size Distribution Measurement
2.2.8. Evaluation of Granules Flow Properties and Compressibility
2.2.9. Determination of Carvedilol Content
2.2.10. Granules Surface Morphology
2.2.11. Assessment of Carvedilol Physical State
2.2.12. Compaction into SMEDDS Tablets
2.2.13. Evaluation of SMEDDS Tablets
2.2.14. Evaluation of Self-Microemulsifying Properties
2.2.15. In Vitro Dissolution Testing
3. Results and Discussion
3.1. Formulation Development and Characterization of SMEDDS Granules
3.1.1. Manual Wet Granulation with SMEDDS-Based Granulation Dispersion
3.1.2. High-Shear Granulation with SMEDDS-Based Granulation Dispersion
3.1.3. The Impact of Carrier Type and Granulation Method on SMEDDS Granules Surface Morphology
3.1.4. Carvedilol Physical State in SMEDDS Granules
3.2. Formulation Development and Characterization of SMEDDS Orodispersable Tablets
3.3. Improvement of Carvedilol In Vitro Dissolution Properties and Self-Microemulsifying Properties of Solid SMEDDS
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Mesoporous Carrier | Impeller Speed (rpm) | Chopper Speed (rpm) |
---|---|---|
Syloid® 244FP | 400 | 2000 |
Neusilin® US2 | 500 | 2000 |
Liquid flow of GD was 4.3 g/min |
Formulation Name | Mesoporous Carrier | GD Added (g) per 1 g of the Carrier | % Povidone K25 in GD | Liquid Added (g) per 1 g of the Carrier | % SMEDDS in Dry Granules | Process Yield (%) | Moisture Content (%) |
---|---|---|---|---|---|---|---|
Gm SYL244 | Syloid® 244FP | 2.87 | 7 | 2.68 | 63.7 | 90.4 | 2.18 |
Gm NEU | Neusilin® US2 | 3.27 | 7 | 3.03 | 66.3 | 77.2 | 2.87 |
Gm FUJ | Fujicalin® SG | 0.92 | 5 | 0.88 | 36.9 | 89.5 | 2.26 |
Gm SYL3050 | Syloid® XDP 3050 | 2.56 | 25 | 1.93 | 44.3 | 89.4 | 2.11 |
Gm AER | Aeroperl® 300 | 2.51 | 15 | 2.14 | 53.1 | 87.6 | 2.61 |
Ghs SYL244 | Syloid® 244FP | 2.33 | 7 | 2.18 | 59.7 | 94.2 | 2.71 |
Ghs NEU | Neusilin® US2 | 2.27 | 7 | 2.12 | 59.3 | 73.9 | 4.18 |
Sample | d50 (µm) | SPAN | Flow Properties | ||
---|---|---|---|---|---|
Angle of Repose (°) | Flow Time (s) | Carr Index (%) | |||
Gm SYL244 | 448 | 1.85 | 18.0 ± 1.7 | 8.8 ± 0.3 | 19.2 ± 4.2 |
Gm NEU | 529 | 1.22 | 24.3 ± 1.4 | 12.5 ± 1.3 | 22.9 ± 1.8 |
Gm FUJ | 609 | 0.93 | 25.4 ± 0.7 | 11.7 ± 0.4 | 18.4 ± 1.0 |
Gm SYL3050 | 791 | 1.25 | 21.4 ± 1.3 | 13.5 ± 1.2 | 35.7 ± 1.5 |
Gm AER | 623 | 0.84 | 16.7 ± 1.5 | 7.9 ± 0.2 | 21.4 ± 0.5 |
Ghs SYL244 | 366 | 1.90 | 20.5 ± 2.3 | 5.8 ± 0.4 | 15.9 ± 0.9 |
Ghs NEU | 329 | 1.85 | 25.3 ± 1.4 | 9.6 ± 0.5 | 16.4 ± 0.5 |
Composition % w/w * | Syloid® 244FP | Neusilin® US2 | |||||
---|---|---|---|---|---|---|---|
Tableting Mixture | Ghs NEU/SYL244 | Kollidon® VA64 | Ac-Di-Sol® | Compression Force (kN) | Hardness (N) | Compression Force (kN) | Hardness (N) |
TM0 | 100 | 0 | 0 | 15.5 | 13.0 | 14.9 | 24.2 |
TM1 | 50 | 5 | 5 | 17.4 | 34.9 | 15.1 | 34.2 |
TM2 | 50 | 10 | 5 | 16.3 | 35.4 | 15.1 | 37.3 |
TM3 | 50 | 5 | 3 | 15.1 | 32.8 | 15.4 | 39.5 |
TM4 | 25 | 5 | 5 | 9.5 | 94.8 | 9.5 | 121.5 |
10.9 | 121.2 | 10.5 | 137.4 |
Sample | Media | z-Average Diameter (nm) | Peak 1 (nm) | Peak 2 (nm) | PDI |
---|---|---|---|---|---|
SMEDDS dispersion (without carvedilol) | water | 23.1 ± 0.2 | 23.1 | / | 0.07 ± 0.00 |
pH = 1.2 | 25.8 ± 1.6 | 25.4 | 2139 | 0.27 ± 0.05 | |
pH = 6.8 | 23.7 ± 0.0 | 25.1 | 4293 | 0.20 ± 0.01 | |
SMEDDS dispersion (with carvedilol) | water | 81.6 ± 1.2 | 21.9 | 149.4 | 0.46 ± 0.00 |
pH = 1.2 | 19.2 ± 0.2 | 20.9 | 4576 | 0.14 ± 0.02 | |
pH = 6.8 | 30.9 ± 0.0 | 34.3 | 747.6 | 0.23 ± 0.02 | |
Gm SYL244 | water | 27.2 ± 0.2 | 28.1 | 248.8 | 0.32 ± 0.00 |
pH = 1.2 | 28.4 ± 0.2 | 24.0 | 71.0 | 0.37 ± 0.00 | |
pH = 6.8 | 41.2 ± 0.2 | 33.7 | 139.7 | 0.37 ± 0.01 | |
Gm NEU | water | 21.8 ± 0.0 | 23.3 | 4155 | 0.19 ± 0.01 |
pH = 1.2 | 23.6 ± 0.3 | 24.3 | 1343 | 0.24 ± 0.01 | |
pH = 6.8 | 24.7 ± 0.1 | 26.1 | 3564 | 0.21 ± 0.01 | |
Gm FUJ | water | 19.7 ± 0.0 | 22.1 | / | 0.13 ± 0.00 |
pH = 1.2 | 25.5 ± 0.2 | 26.2 | 332.2 | 0.28 ± 0.02 | |
pH = 6.8 | 30.3 ± 0.0 | 39.5 | 2992 | 0.28 ± 0.02 | |
Gm SYL3050 | water | 19.9 ± 0.1 | 23.0 | 4255 | 0.16 ± 0.01 |
pH = 1.2 | 40.5 ± 0.5 | 23.1 | 142.9 | 0.47 ± 0.01 | |
pH = 6.8 | 35.4 ± 0.2 | 27.0 | 181.9 | 0.43 ± 0.01 | |
Gm AER | water | 22.1 ± 0.1 | 22.9 | 1254 | 0.26 ± 0.01 |
pH = 1.2 | 28.4 ± 0.2 | 24.7 | 200.4 | 0.38 ± 0.01 | |
pH = 6.8 | 25.7 ± 0.2 | 26.5 | 741.1 | 0.25 ± 0.00 | |
Ghs SYL244 | water | 44.9 ± 0.4 | 29.1 | 152.8 | 0.47 ± 0.02 |
pH = 1.2 | 25.2 ± 0.1 | 23.8 | 250.2 | 0.31 ± 0.01 | |
pH = 6.8 | 56.8 ± 0.3 | 27.6 | 125.9 | 0.42 ± 0.00 | |
Ghs NEU | water | 22.8 ± 0.0 | 22.4 | 3992 | 0.20 ± 0.01 |
pH = 1.2 | 22.4 ± 0.1 | 23.9 | 4442 | 0.18 ± 0.00 | |
pH = 6.8 | 25.1 ± 0.2 | 27.2 | 3652 | 0.21 ± 0.01 | |
T-SYL244 | water | 72.2 ± 0.4 | 25.5 | 151.4 | 0.50 ± 0.00 |
pH = 1.2 | 55.4 ± 0.4 | 22.7 | 175.8 | 0.57 ± 0.00 | |
pH = 6.8 | 74.6 ± 0.9 | 26.9 | 169.2 | 0.52 ± 0.02 | |
T-NEU | water | 78.0 ± 1.1 | 26.1 | 218.8 | 0.62 ± 0.02 |
pH = 1.2 | 36.0 ± 1.6 | 56.1 | 4454 | 0.33 ± 0.02 | |
pH = 6.8 | 45.1 ± 0.4 | 34.4 | 175.5 | 0.44 ± 0.00 |
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Kovačević, M.; German Ilić, I.; Bolko Seljak, K.; Zvonar Pobirk, A. High-Shear Wet Granulation of SMEDDS Based on Mesoporous Carriers for Improved Carvedilol Solubility. Pharmaceutics 2022, 14, 2077. https://doi.org/10.3390/pharmaceutics14102077
Kovačević M, German Ilić I, Bolko Seljak K, Zvonar Pobirk A. High-Shear Wet Granulation of SMEDDS Based on Mesoporous Carriers for Improved Carvedilol Solubility. Pharmaceutics. 2022; 14(10):2077. https://doi.org/10.3390/pharmaceutics14102077
Chicago/Turabian StyleKovačević, Mila, Ilija German Ilić, Katarina Bolko Seljak, and Alenka Zvonar Pobirk. 2022. "High-Shear Wet Granulation of SMEDDS Based on Mesoporous Carriers for Improved Carvedilol Solubility" Pharmaceutics 14, no. 10: 2077. https://doi.org/10.3390/pharmaceutics14102077
APA StyleKovačević, M., German Ilić, I., Bolko Seljak, K., & Zvonar Pobirk, A. (2022). High-Shear Wet Granulation of SMEDDS Based on Mesoporous Carriers for Improved Carvedilol Solubility. Pharmaceutics, 14(10), 2077. https://doi.org/10.3390/pharmaceutics14102077