Flurbiprofen-Loaded Solid SNEDDS Preconcentrate for the Enhanced Solubility, In-Vitro Dissolution and Bioavailability in Rats
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. HPLC Condition
2.3. Solubility Test
2.4. Characterization of Various Vehicle Compositions
2.5. Particle Size Measurement
2.6. Differential Scanning Calorimetry (DSC)
2.7. Construction of Pseudo-Ternary Phase Diagram
- C = predetermined composition (%) of Kollisolv MCT 70. D = predetermined composition (%) of TPGS. C + D + E = 100%.
2.8. Powder X-ray Diffraction (PXRD)
2.9. Dissolution Test
2.10. Oral Pharmacokinetic Study in Rats
2.11. Data Analysis
3. Results and Discussion
3.1. Solubility Test
3.2. Characterization of Various Vehicle Compositions
3.3. Construction of Pseudo-Ternary Phase Diagram
3.4. Particle Size and Peak Melting Temperature
3.5. Differential Scanning Calorimetry (DSC)
3.6. Powder X-ray Diffraction (PXRD)
3.7. Dissolution Test
3.8. Oral Pharmacokinetics
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Composition (Weight Ratio) | Physical State at 25 °C | Particle Size (nm, mean ± S.D., n = 3) | Peak Melting Temperature (°C, n = 1) | ||
---|---|---|---|---|---|
Kollisolv MCT 70 | Gelucire 44/14 | 1/3 | Solid | 354.42 ± 21.82 | 41.68 |
2/2 | Solid | 445.73 ± 34.30 | 41.22 | ||
3/1 | Solid | 571.91 ± 40.48 | 40.99 | ||
Kolliphor HS 15 | 1/3 | Solid | 129.40 ± 2.31 | 27.31 | |
2/2 | Liquid | 196.35 ± 18.73 | No peak | ||
3/1 | Liquid | 490.63 ± 63.16 | No peak | ||
TPGS | 1/3 | Solid | 132.12 ± 10.51 | 36.96 | |
2/2 | Solid | 278.95 ± 26.25 | 36.58 | ||
3/1 | Solid | 396.63 ± 21.34 | 36.37 | ||
Lauroglycol 90 | Gelucire 44/14 | 1/3 | Solid | 533.96 ± 78.33 | 35.55 |
2/2 | Solid | 546.20 ± 50.48 | 34.92 | ||
3/1 | Solid | 592.21 ± 68.34 | 32.66 | ||
Kolliphor HS 15 | 1/3 | Liquid | 228.95 ± 16.85 | No peak | |
2/2 | Liquid | 475.82 ± 35.43 | No peak | ||
3/1 | Liquid | 795.76 ± 104.22 | No peak | ||
TPGS | 1/3 | Solid | 262.11 ± 30.47 | 36.70 | |
2/2 | Liquid | 556.73 ± 45.61 | No peak | ||
3/1 | Liquid | 598.68 ± 61.63 | No peak | ||
Capmul MCM C8 | Gelucire 44/14 | 1/3 | Solid | 171.30 ± 27.38 | 33.28 |
2/2 | Liquid | 280.14 ± 56.94 | No peak | ||
3/1 | Liquid | 490.26 ± 62.36 | No peak | ||
Kolliphor HS 15 | 1/3 | Liquid | 98.16 ± 2.63 | No peak | |
2/2 | Liquid | 134.21 ± 9.45 | No peak | ||
3/1 | Liquid | 312.86 ± 53.72 | No peak | ||
TPGS | 1/3 | Solid | 133.47 ± 4.34 | 35.36 | |
2/2 | Liquid | 259.23 ± 9.10 | No peak | ||
3/1 | Liquid | 421.85 ± 48.53 | No peak |
Formulation | Composition (Weight %) | Particle Size (nm, mean ± S.D., n = 3) | Peak Melting Temperature (°C, n = 1) | ||
---|---|---|---|---|---|
FL | Kollisolv MCT 70 | TPGS | |||
F1 | 10 | 0 | 90 | 26.82 ± 2.25 | 33.59 |
F2 | 10 | 10 | 80 | 13.74 ± 2.21 | 32.37 |
F3 | 10 | 20 | 70 | 17.03 ± 2.31 | 31.52 |
F4 | 10 | 30 | 60 | 31.42 ± 5.29 | 30.74 |
F5 | 10 | 70 | 20 | 594.38 ± 113.15 | Liquid |
F6 | 20 | 0 | 80 | 190.46 ± 48.37 | 26.13/30.72 |
F7 | 20 | 10 | 70 | 186.81 ± 24.21 | Semi-solid |
F8 | 30 | 0 | 70 | 245.24 ± 67.09 | Liquid |
F9 | 30 | 10 | 60 | 817.13 ± 128.77 | Liquid |
Vehicle | * Solubility (w/w%) |
---|---|
Oils | |
Kollisolv MCT 70 | 24.85 ± 0.20 |
Lauroglycol 90 | 22.43 ± 0.92 |
Capmul MCM C8 | 21.38 ± 0.95 |
Solid or Semisolid Surfactants | |
Gelucire 44/14 | 33.09 ± 1.44 |
Kolliphor HS 15 | 31.97 ± 2.45 |
TPGS | 34.28 ± 4.26 |
Pharmacokinetic Parameters | FL Suspension | F2 |
---|---|---|
Tmax (min) | 228 ± 89 | 60.0 ± 34.6* |
Cmax (μg /mL) | 19.6 ± 3.8 | 44.1 ± 3.4 |
T1/2 (min) | 282 ± 73 | 340 ± 49 |
AUClast (μg∙min/mL) | 12700 ± 2052 | 24200 ± 2886* |
AUC∞ (μg∙min/mL) | 13200 ± 2279 | 25500 ± 2531* |
MRT a (min) | 448 ± 76 | 462 ± 34 |
Relative BA b (%) | - | 193 |
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Kim, R.M.; Jang, D.-J.; Kim, Y.C.; Yoon, J.-H.; Min, K.A.; Maeng, H.-J.; Cho, K.H. Flurbiprofen-Loaded Solid SNEDDS Preconcentrate for the Enhanced Solubility, In-Vitro Dissolution and Bioavailability in Rats. Pharmaceutics 2018, 10, 247. https://doi.org/10.3390/pharmaceutics10040247
Kim RM, Jang D-J, Kim YC, Yoon J-H, Min KA, Maeng H-J, Cho KH. Flurbiprofen-Loaded Solid SNEDDS Preconcentrate for the Enhanced Solubility, In-Vitro Dissolution and Bioavailability in Rats. Pharmaceutics. 2018; 10(4):247. https://doi.org/10.3390/pharmaceutics10040247
Chicago/Turabian StyleKim, Rae Man, Dong-Jin Jang, Yu Chul Kim, Jin-Ha Yoon, Kyoung Ah Min, Han-Joo Maeng, and Kwan Hyung Cho. 2018. "Flurbiprofen-Loaded Solid SNEDDS Preconcentrate for the Enhanced Solubility, In-Vitro Dissolution and Bioavailability in Rats" Pharmaceutics 10, no. 4: 247. https://doi.org/10.3390/pharmaceutics10040247
APA StyleKim, R. M., Jang, D.-J., Kim, Y. C., Yoon, J.-H., Min, K. A., Maeng, H.-J., & Cho, K. H. (2018). Flurbiprofen-Loaded Solid SNEDDS Preconcentrate for the Enhanced Solubility, In-Vitro Dissolution and Bioavailability in Rats. Pharmaceutics, 10(4), 247. https://doi.org/10.3390/pharmaceutics10040247