Development and Evaluation of a Reconstitutable Dry Suspension to Improve the Dissolution and Oral Absorption of Poorly Water-Soluble Celecoxib
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Preparation of Nanosuspension and Dry Suspension
2.2.1. Preparation of Nanosuspension Using Wet Bead Milling
2.2.2. Preparation of Dry Suspension Using Spray-Drying
2.3. Characterizations of Nanosuspension and RDS
2.3.1. Particle Size, Distribution and Zeta Potential Analysis
2.3.2. Redispersibility
2.3.3. Scanning Electron Microscopy (SEM)
2.3.4. Solid-State Characterization
2.3.5. Physical Stability
2.3.6. In Vitro Dissolution Test
2.3.7. In Vivo Oral Pharmacokinetic Studies in Rats
3. Results and Discussion
3.1. Morphology of Nanosuspension and Reconstitutable Dry Suspension
3.2. Characterizations of Suspension System
3.2.1. Particle Size and Redispersibility
3.2.2. Solid-State Characterization
3.2.3. Physical Stability
3.3. Dissolution Study
3.4. Pharmacokinetic Study
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Formulation | Time (Week) | Particle Size (nm) | SPAN | PDI | RDI (%) | Zeta Potential (mV) |
---|---|---|---|---|---|---|
Nano Suspension | 0 | 713.0 ± 25.3 | 1.31 ± 0.03 | 0.24 ± 0.01 | −19.0 ± 1.9 | |
2 | 711.1 ± 15.5 | 1.26 ± 0.02 | 0.24 ± 0.01 | |||
4 | 760.9 ± 66.5 | 1.24 ± 0.03 | 0.23 ± 0.02 | |||
8 | 923.0 ± 56.4 | 1.14 ± 0.04 | 0.20 ± 0.03 | |||
12 | 965.9 ± 170.9 | 1.43 ± 0.06 | 0.35 ± 0.05 | −7.7 ± 0.8 | ||
RDS | 0 | 775.8 ± 11.6 | 1.32 ± 0.04 | 0.26 ± 0.04 | 108 | −15.8 ± 1.5 |
2 | 756.7 ± 11.0 | 1.38 ± 0.03 | 0.29 ± 0.02 | 106 | ||
4 | 762.9 ± 23.4 | 1.35 ± 0.03 | 0.28 ± 0.03 | 107 | ||
8 | 769.0 ± 5.00 | 1.40 ± 0.05 | 0.32 ± 0.03 | 108 | ||
12 | 758.7 ± 44.1 | 1.35 ± 0.03 | 0.25 ± 0.02 | 106 | −15.5 ± 2.5 |
Pharmacokinetic Parameters | CXB Powder | RDS | Market Product |
---|---|---|---|
Tmax (min) | 420 ± 69 | 405 ± 150 | 195 ± 57 |
Cmax (μg /mL) | 0.26 ± 0.08 | 1.49 ± 0.29 | 1.64 ± 0.31 |
T1/2 (min) | 345 ± 70 | 357 ± 56 | 295 ± 66 |
AUClast (μg∙min/mL) | 304 ± 85 | 1904 ± 350 | 1844 ± 316 |
AUC∞ (μg∙min/mL) | 305 ± 85 | 1910 ± 353 | 1847 ± 318 |
MRT (min) a | 789 ± 148 | 888 ± 22 | 684 ± 79 |
Relative BA (%) | 625 | 605 |
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Kim, H.-I.; Park, S.Y.; Park, S.J.; Lee, J.; Cho, K.H.; Jee, J.-P.; Kim, H.-C.; Maeng, H.-J.; Jang, D.-J. Development and Evaluation of a Reconstitutable Dry Suspension to Improve the Dissolution and Oral Absorption of Poorly Water-Soluble Celecoxib. Pharmaceutics 2018, 10, 140. https://doi.org/10.3390/pharmaceutics10030140
Kim H-I, Park SY, Park SJ, Lee J, Cho KH, Jee J-P, Kim H-C, Maeng H-J, Jang D-J. Development and Evaluation of a Reconstitutable Dry Suspension to Improve the Dissolution and Oral Absorption of Poorly Water-Soluble Celecoxib. Pharmaceutics. 2018; 10(3):140. https://doi.org/10.3390/pharmaceutics10030140
Chicago/Turabian StyleKim, Hye-In, Sang Yeob Park, Seok Ju Park, Jewon Lee, Kwan Hyung Cho, Jun-Pil Jee, Hee-Cheol Kim, Han-Joo Maeng, and Dong-Jin Jang. 2018. "Development and Evaluation of a Reconstitutable Dry Suspension to Improve the Dissolution and Oral Absorption of Poorly Water-Soluble Celecoxib" Pharmaceutics 10, no. 3: 140. https://doi.org/10.3390/pharmaceutics10030140
APA StyleKim, H.-I., Park, S. Y., Park, S. J., Lee, J., Cho, K. H., Jee, J.-P., Kim, H.-C., Maeng, H.-J., & Jang, D.-J. (2018). Development and Evaluation of a Reconstitutable Dry Suspension to Improve the Dissolution and Oral Absorption of Poorly Water-Soluble Celecoxib. Pharmaceutics, 10(3), 140. https://doi.org/10.3390/pharmaceutics10030140