Development of Lipid-Based Gastroretentive Delivery System for Gentian Extract by Double Emulsion–Melt Dispersion Technique
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Gentian Extract Preparation
2.3. Preparation of Double W/O/W Emulsion
2.4. Characterization of Double Emulsions
2.4.1. Conductometric Analysis
2.4.2. Centrifugation Test
2.4.3. Microscopic Analysis
2.5. Preparation of Solid Lipid Microparticles
2.6. Characterization of Solid Lipid Microparticles
2.6.1. Scanning Electron Microscopy
2.6.2. Determination of the Encapsulation Efficiency
2.6.3. High-Performance Liquid Chromatography
2.6.4. Determination of Yield
2.6.5. Mercury Intrusion Porosimetry
2.6.6. Flow Properties Evaluation
2.6.7. Tablets Preparation and Determination of Mechanical Properties
2.6.8. In Vitro Gentiopicroside Dissolution Testing
2.6.9. Kinetic Modeling of Gentiopicroside Release
2.6.10. Assessment of Dispersibility during In Vitro Dissolution
2.6.11. Mucoadhesion Evaluation
3. Results and Discussion
3.1. Double Emulsions Development
3.2. Solid Lipid Microparticles Characterization
3.2.1. Morphology
3.2.2. Yield and Encapsulation Efficiency
3.2.3. Porosity
3.2.4. Flowability
3.2.5. Mechanical Properties
3.2.6. Mucoadhesivity Evaluation
3.2.7. In Vitro Gentiopicroside Release
3.2.8. Dispersibility during In Vitro Dissolution
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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A | B | C | D | |
---|---|---|---|---|
Gentian extract (%) | 66.5 | 66.5 | 66.5 | 66.5 |
Sodium alginate (%) | 1.3 | 1.3 | 1.3 | 1.3 |
Sodium chloride (M) | 0.05 | 0.05 | 0.05 | 0.05 |
Gelucire® 39/01 (%) * | 26.9 | 26.9 | / | / |
Gelucire® 43/01 (%) ** | / | / | 26.9 | 26.9 |
Lipophilic emulsifier (%) *** | 5.0 | 5.0 | 5.0 | 5.0 |
A | B | C | D | |
---|---|---|---|---|
Primary emulsion with PGPR (%) * | 19.8 | 19.8 | 19.8 | 19.8 |
Sodium alginate (%) | 2 | 2 | 2 | 2 |
Sodium chloride (%) | 0.05 | 0.2 | 0.2 | 0.2 |
Hydrophilic emulsifier (%) ** | 1.6 | 1.6 | 1.6 | 1.6 |
Trehalose (%) | 7.9 | 7.9 | 7.9 | 7.9 |
Sylysia® 350 (%) | / | 1.0 | / | 1.0 |
Purified water to (%) | 100.0 | 100.0 | 100.0 | 100.0 |
Sample | A | B | C | D |
---|---|---|---|---|
EE (%) *,** | 98.92 ± 1.06 a | 103.02 ± 0.15 ab | 98.77 ± 4.28 a | 104.32 ± 0.16 b |
Yield (%) ** | 92.05 ± 1.48 a | 95.17 ± 1.03 a | 91.85 ± 2.03 a | 93.57 ± 1.87 a |
Sample | Run | Dav (µm) | BD (g/cm3) | P (%) |
---|---|---|---|---|
A | I | 9.78 | 1.03 | 24.7 |
II | 9.78 | 1.03 | 16.2 | |
B | I | 9.78 | 0.95 | 32.8 |
II | 9.00 | 0.95 | 16.7 | |
C | I | 6.29 | 0.93 | 29.9 |
II | 9.78 | 0.93 | 17.3 | |
D | I | 9.0 | 0.93 | 32.4 |
II | 9.0 | 0.93 | 21.3 | |
Dry gentian extract | I | 9.8 | 1.22 | 20.2 |
II | 0.01 | 1.22 | 3.1 |
Sample | Hausner Ratio | Carr Index (%) | Flowability |
---|---|---|---|
A | 1.13 ± 0.04 | 11.84 ± 3.11 | good |
B | 1.23 ± 0.02 | 18.67 ± 1.26 | fair |
C | 1.10 ± 0.02 | 9.73 ± 1.48 | excellent |
D | 1.12 ± 0.03 | 10.64 ± 2.18 | good |
Dry gentian extract | 1.28 ± 0.08 | 21.95 ± 5.26 | passable |
Sample | A | B | C | D |
---|---|---|---|---|
The force of adhesion (N) * | 1.73 ± 0.66 a | 2.02 ± 0.46 a | 2.08 ± 0.64 a | 2.46 ± 0.12 a |
Sample | Correlation Coefficients (r2) | |||
---|---|---|---|---|
Zero-order | First-order | Higuchi | Korsmeyer–Peppas | |
A | 0.6241 | 0.4783 | 0.8422 | 0.8524 |
B | 0.7433 | 0.7319 | 0.9423 | 0.9819 |
C | 0.7268 | 0.6628 | 0.9339 | 0.9601 |
D | 0.7279 | 0.6600 | 0.9339 | 0.9601 |
Time | 15 min | 6 h | ||||||
---|---|---|---|---|---|---|---|---|
Peak | Peak 1 | Peak 2 | Peak 1 | Peak 2 | ||||
Sample | D (nm) | I (%) | D (nm) | I (%) | D (nm) | I (%) | D (nm) | I (%) |
A | 73.4 | 100.0 | / | / | 147.4 | 100.0 | / | / |
B | 210.2 | 96.3 | 5319.0 | 3.7 | 126.4 | 98.2 | 5236.0 | 1.8 |
C | 389.6 | 100.0 | / | / | 140.1 | 100.0 | / | / |
D | 165.5 | 94.1 | 5271.0 | 5.9 | 239.3 | 93.0 | 5007.0 | 7.0 |
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Mudrić, J.; Šavikin, K.; Đekić, L.; Pavlović, S.; Kurćubić, I.; Ibrić, S.; Đuriš, J. Development of Lipid-Based Gastroretentive Delivery System for Gentian Extract by Double Emulsion–Melt Dispersion Technique. Pharmaceutics 2021, 13, 2095. https://doi.org/10.3390/pharmaceutics13122095
Mudrić J, Šavikin K, Đekić L, Pavlović S, Kurćubić I, Ibrić S, Đuriš J. Development of Lipid-Based Gastroretentive Delivery System for Gentian Extract by Double Emulsion–Melt Dispersion Technique. Pharmaceutics. 2021; 13(12):2095. https://doi.org/10.3390/pharmaceutics13122095
Chicago/Turabian StyleMudrić, Jelena, Katarina Šavikin, Ljiljana Đekić, Stefan Pavlović, Ivana Kurćubić, Svetlana Ibrić, and Jelena Đuriš. 2021. "Development of Lipid-Based Gastroretentive Delivery System for Gentian Extract by Double Emulsion–Melt Dispersion Technique" Pharmaceutics 13, no. 12: 2095. https://doi.org/10.3390/pharmaceutics13122095
APA StyleMudrić, J., Šavikin, K., Đekić, L., Pavlović, S., Kurćubić, I., Ibrić, S., & Đuriš, J. (2021). Development of Lipid-Based Gastroretentive Delivery System for Gentian Extract by Double Emulsion–Melt Dispersion Technique. Pharmaceutics, 13(12), 2095. https://doi.org/10.3390/pharmaceutics13122095