Spray-Dried Powder Formulation of Capreomycin Designed for Inhaled Tuberculosis Therapy
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Preparation of Spray-Dried Powders
2.3. Drug Content
2.4. Morphology Study
2.5. Particle Size Distribution
2.6. In Vitro Aerosol Performance
2.7. Thermogravimetric Analysis (TGA)
2.8. Differential Scanning Calorimetry (DSC)
2.9. Powder X-ray Diffraction (PXRD)
2.10. X-ray Photoelectron Spectroscopy (XPS)
2.11. Animal Study
2.12. Pharmacokinetic Study
2.13. Extraction of Capreomycin
2.14. Data Analysis
3. Results
3.1. Production Yield of Spray Drying
3.2. Drug Content and Residual Moisture
3.3. Particle Morphology
3.4. Particle Size Distribution
3.5. In Vitro Aerosol Performance
3.6. Thermoanalysis and Powder Crystallinity
3.7. Surface Composition
3.8. Pharmacokinetic Study
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Sample Name | Capreomycin: Mannitol Ratio (w/w) | Capreomycin Percentage by Mass | Inlet Temperature (°C) |
---|---|---|---|
C20_T60 | 1:4 | 20.0 | 60 |
C20_T90 | 90 | ||
C20_T120 | 120 | ||
C20_T150 | 150 | ||
C25_T60 | 1:3 | 25.0 | 60 |
C25_T90 | 90 | ||
C25_T120 | 120 | ||
C25_T150 | 150 | ||
C33_T60 | 1:2 | 33.3 | 60 |
C33_T90 | 90 | ||
C33_T120 | 120 | ||
C33_T150 | 150 | ||
C50_T60 | 1:1 | 50.0 | 60 |
C50_T90 | 90 | ||
C50_T120 | 120 | ||
C50_T150 | 150 |
Sample Name | Outlet Temperature (°C) | Production Yield (%, w/w) | Drug Content (%, w/w) | Residual Moisture (%, w/w) |
---|---|---|---|---|
C20_T60 | 36–38 | 53.0 | 19.2 ± 0.4 | 2.2 |
C20_T90 | 52–55 | 69.9 | 18.7 ± 1.4 | 1.2 |
C20_T120 | 70–74 | 66.9 | 19.8 ± 0.3 | 1.6 |
C20_T150 | 90–95 | 63.3 | 19.0 ± 0.6 | 1.4 |
C25_T60 | 35–39 | 47.3 | 25.5 ± 0.3 | 2.3 |
C25_T90 | 52–56 | 65.7 | 24.9 ± 0.6 | 0.7 |
C25_T120 | 68–71 | 78.1 | 26.7 ± 0.4 | 1.5 |
C25_T150 | 83–86 | 63.9 | 24.5 ± 0.8 | 0.5 |
C33_T60 | 34–37 | 18.2 | 33.2 ± 0.6 | 3.1 |
C33_T90 | 53–56 | 25.8 | 33.6 ± 0.4 | 2.8 |
C33_T120 | 68–70 | 52.5 | 34.4 ± 0.8 | 2.0 |
C33_T150 | 88–92 | 39.1 | 34.1 ± 0.2 | 2.8 |
C50_T60 | 34–37 | 1.0 | N.A. | N.A. |
C50_T90 | 52–57 | 6.9 | N.A. | N.A. |
C50_T120 | 66–68 | 4.3 | N.A. | N.A. |
C50_T150 | 84–87 | 7.2 | N.A. | N.A. |
Sample | Volumetric Diameter | Aerodynamic Diameter | ||||
---|---|---|---|---|---|---|
D10 (μm) | D50 (μm) | D90 (μm) | Span Value | MMAD (μm) | GSD | |
C20_T60 | 1.21 ± 0.02 | 2.67 ± 0.02 | 5.20 ± 0.14 | 1.49 ± 0.03 | 4.29 ± 0.77 | 3.09 ± 0.14 |
C20_T90 | 1.20 ± 0.02 | 2.52 ± 0.00 | 4.59 ± 0.10 | 1.35 ± 0.05 | 4.28 ± 0.85 | 3.30 ± 0.28 |
C20_T120 | 0.76 ± 0.03 | 1.82 ± 0.06 | 3.47 ± 0.04 | 1.49 ± 0.07 | 4.58 ± 0.37 | 3.89 ± 0.33 |
C20_T150 | 1.66 ± 0.04 | 5.36 ± 0.17 | 10.67 ± 0.44 | 1.68 ± 0.03 | 9.85 ± 1.15 | 4.02 ± 0.63 |
C25_T60 | 1.32 ± 0.08 | 3.07 ± 0.09 | 6.51 ± 0.37 | 1.69 ± 0.07 | 4.46 ± 0.21 | 2.45 ± 0.25 |
C25_T90 | 1.16 ± 0.01 | 2.62 ± 0.05 | 5.06 ± 0.16 | 1.49 ± 0.03 | 3.38 ± 0.22 | 2.83 ± 0.14 |
C25_T120 | 0.97 ± 0.03 | 2.44 ± 0.04 | 4.80 ± 0.06 | 1.57 ± 0.03 | 4.28 ± 0.36 | 2.70 ± 0.25 |
C25_T150 | 1.28 ± 0.04 | 5.16 ± 0.14 | 11.73 ± 0.22 | 2.03 ± 0.03 | 8.79 ± 0.38 | 2.72 ± 0.20 |
C33_T60 | 1.57 ± 0.03 | 3.33 ± 0.02 | 6.83 ± 0.15 | 1.58 ± 0.05 | 5.29 ± 0.93 | 3.06 ± 0.06 |
C33_T90 | 1.49 ± 0.05 | 3.16 ± 0.05 | 6.51 ± 0.24 | 1.59 ± 0.05 | 4.74 ± 1.14 | 3.08 ± 0.26 |
C33_T120 | 1.08 ± 0.05 | 2.60 ± 0.11 | 5.17 ± 0.37 | 1.57 ± 0.07 | 4.32 ± 0.34 | 2.35 ± 0.31 |
C33_T150 | 2.16 ± 0.21 | 6.44 ± 0.54 | 15.74 ± 2.83 | 2.10 ± 0.25 | 16.59 ± 2.66 | 3.87 ± 0.31 |
Element | Raw Capreomycin (as Sulfate) | Raw Mannitol | ||
---|---|---|---|---|
Theoretical | Experimental | Theoretical | Experimental | |
Carbon | 47.1 | 57.2 ± 0.2 | 50.0 | 52.7 ± 0.2 |
Oxygen | 23.5 | 19.0 ± 0.1 | 50.0 | 47.3 ± 0.2 |
Nitrogen | 27.5 | 21.7 ± 0.1 | - | - |
Sulphur | 2.0 | 2.1 ± 0.0 | - | - |
Parameters a | Plasma | Lung | ||
---|---|---|---|---|
IT Group | IV Group | IT Group | IV Group | |
Kel (h−1) | 1.15 ± 0.57 | 2.74 ± 1.67 | 0.07 ± 0.04 *** | 2.37 ± 0.23 b |
t1/2 (h) | 0.73 ± 0.33 | 0.34 ± 0.20 | 18.94 ± 20.67 | 0.29 ± 0.03 b |
CL (mL/h·kg) | 321.88 ± 81.65 *** | 612.91 ± 93.46 | 12.99 ± 3.66 *** | 2624.71 ± 157.19 b |
AUC0–t (µg·h/mL) | 65.10 ± 16.37 ** | 32.55 ± 5.52 | 1061.88 ± 235.76 *** | 6.71 ± 0.51 |
AUC0–∞ (µg·h/mL) | 67.26 ± 16.92 ** | 33.78 ± 5.54 | 1726.37 ± 658.83 ** | 7.78 ± 0.46 b |
MRT (h) | 0.79 ± 0.22 ** | 0.30 ± 0.11 | 6.62 ± 1.25 *** | 0.23 ± 0.13 |
Cmax (µg/mL) or (µg/g) c | 80.08 ± 18.84 | 74.89 ± 10.94 | 739.13 ± 180.66 *** | 18.23 ± 8.34 |
Tmax (h) | 0.15 ± 0.09 | 0.08 ± 0 | 0.27 ± 0.20 | 0.12 ± 0.07 |
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Shao, Z.; Tai, W.; Qiu, Y.; Man, R.C.H.; Liao, Q.; Chow, M.Y.T.; Kwok, P.C.L.; Lam, J.K.W. Spray-Dried Powder Formulation of Capreomycin Designed for Inhaled Tuberculosis Therapy. Pharmaceutics 2021, 13, 2044. https://doi.org/10.3390/pharmaceutics13122044
Shao Z, Tai W, Qiu Y, Man RCH, Liao Q, Chow MYT, Kwok PCL, Lam JKW. Spray-Dried Powder Formulation of Capreomycin Designed for Inhaled Tuberculosis Therapy. Pharmaceutics. 2021; 13(12):2044. https://doi.org/10.3390/pharmaceutics13122044
Chicago/Turabian StyleShao, Zitong, Waiting Tai, Yingshan Qiu, Rico C. H. Man, Qiuying Liao, Michael Y. T. Chow, Philip C. L. Kwok, and Jenny K. W. Lam. 2021. "Spray-Dried Powder Formulation of Capreomycin Designed for Inhaled Tuberculosis Therapy" Pharmaceutics 13, no. 12: 2044. https://doi.org/10.3390/pharmaceutics13122044
APA StyleShao, Z., Tai, W., Qiu, Y., Man, R. C. H., Liao, Q., Chow, M. Y. T., Kwok, P. C. L., & Lam, J. K. W. (2021). Spray-Dried Powder Formulation of Capreomycin Designed for Inhaled Tuberculosis Therapy. Pharmaceutics, 13(12), 2044. https://doi.org/10.3390/pharmaceutics13122044