Formulation and Evaluation of Topical Nano-Lipid-Based Delivery of Butenafine: In Vitro Characterization and Antifungal Activity
Abstract
:1. Introduction
2. Result and Discussion
2.1. Optimization
2.2. Effect of Independent Variables on Vesicle Size (Y1)
2.3. Effect of Independent Variables on Entrapment Efficiency (Y2)
2.4. Point Prediction
2.5. Vesicle Size, PDI, and Zeta Potential
2.6. Entrapment Efficiency
2.7. Thermal Analysis
2.8. Development of BN-BSo-Gel
2.9. Viscosity, pH, and Drug Content
2.10. In Vitro Release Study
2.11. In Vitro Permeation Study
2.12. Irritation Study
2.13. Antifungal Study
3. Conclusions
4. Materials and Experimental
4.1. Materials
4.2. Experimental
4.2.1. Preliminary Study
4.2.2. Optimization
4.2.3. Formulation of Bilosomes
4.3. Characterization of BN-BS
4.3.1. Particle Characterization
4.3.2. Entrapment Efficiency
4.3.3. Thermal Analysis
4.3.4. Development of BN-BSs Loaded Gel
4.3.5. Gel Characterization
4.3.6. In Vitro Release Study
4.3.7. Permeation Study
4.3.8. Irritation Study
4.3.9. Antifungal Study
4.3.10. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Formulation Code | Independent Constraints | Dependent Constraints | |||
---|---|---|---|---|---|
Lipid (%) | Surfactant (mg) | Bile Salt (mg) | Vesicle Size (nm) | Entrapment Efficiency (%) | |
A | B | C | Y1 | Y2 | |
F1 | 1.5 | 30 | 20 | 181.5 ± 4.5 | 67.79 ± 1.5 |
F2 | 4.5 | 30 | 20 | 310.1 ± 7.4 | 85.99 ± 1.8 |
F3 | 1.5 | 60 | 20 | 144.4 ± 4.8 | 76.88 ± 1.4 |
F4 | 4.5 | 60 | 20 | 222.8 ± 5.2 | 91.29 ± 2.1 |
F5 | 1.5 | 45 | 15 | 180.8 ± 3.5 | 69.87 ± 1.3 |
F6 | 4.5 | 45 | 15 | 262.7 ± 6.2 | 87.56 ± 1.8 |
F7 | 1.5 | 45 | 25 | 168.9 ± 4.1 | 72.12 ± 1.4 |
F8 | 4.5 | 45 | 25 | 276.3 ± 6.3 | 86.99 ± 1.7 |
F9 | 3 | 30 | 15 | 268.2 ± 5.9 | 77.38 ± 1.4 |
F10 | 3 | 60 | 15 | 208.2 ± 4.2 | 80.99 ± 1.6 |
F11 | 3 | 30 | 25 | 258.8 ± 5.7 | 75.46 ± 1.4 |
F12 | 3 | 60 | 25 | 195.3 ± 4.5 | 86.50 ± 1.7 |
F13 * | 3 | 45 | 20 | 209.6 ± 4.7 | 80.23 ± 2.7 |
F14 * | 3 | 45 | 20 | 208.1 ± 4.4 | 80.98 ± 2.1 |
F15 * | 3 | 45 | 20 | 209.3 ± 3.5 | 80.12 ± 1.4 |
F16 * | 3 | 45 | 20 | 209.9 ± 4.8 | 80.21 ± 1.9 |
F17 * | 3 | 45 | 20 | 207.9 ± 5.1 | 80.56 ± 1.3 |
Model | Y₁ (Vesicle Size, nm) | ||||
---|---|---|---|---|---|
SD | R² | Adjusted R² | Predicted R² | p-Value | |
Linear | 12.85 | 0.9275 | 0.9108 | 0.8625 | <0.0001 |
2FI | 11.54 | 0.9551 | 0.9281 | 0.8283 | 0.1717 |
Quadratic | 5.36 | 0.9932 | 0.9845 | 0.9328 | 0.0029 |
Y₂ (Entrapment efficiency, %) | |||||
Linear | 1.37 | 0.9634 | 0.9549 | 0.9242 | <0.0001 |
2FI | 0.70 | 0.9926 | 0.9881 | 0.9654 | 0.0009 |
Quadratic | 0.38 | 0.9985 | 0.9966 | 0.9876 | 0.0077 |
Source | Particle Size (nm) | Entrapment Efficiency (%) | ||||||
---|---|---|---|---|---|---|---|---|
Sum of the Square | DF | F-Value | p-Value | Sum of the Square | DF | F-Value | p-Value | |
Model | 29,427.84 | 9 | 114.00 | <0.0001 * | 663.11 | 9 | 521.14 | <0.0001 * |
A | 19,700.13 | 1 | 686.83 | <0.0001 * | 530.89 | 1 | 3755.08 | <0.0001 * |
B | 7727.73 | 1 | 269.42 | <0.0001 * | 105.42 | 1 | 745.62 | <0.0001 * |
C | 52.69 | 1 | 1.84 | 0.2174 ** | 3.47 | 1 | 24.56 | 0.0016 * |
AB | 651.02 | 1 | 22.70 | 0.0020 * | 3.59 | 1 | 25.40 | 0.0015 * |
AC | 162.31 | 1 | 5.66 | 0.0490 * | 1.99 | 1 | 14.06 | 0.0072 * |
BC | 3.12 | 1 | 0.11 | 0.7514 ** | 13.80 | 1 | 97.62 | <0.0001 * |
A2 | 49.05 | 1 | 1.71 | 0.2323 ** | 0.29 | 1 | 2.08 | 0.1929 ** |
B2 | 206.58 | 1 | 7.20 | 0.0314 * | 1.97 | 1 | 13.91 | 0.0074 * |
C2 | 855.84 | 1 | 29.84 | 0.0009 * | 1.88 | 1 | 13.33 | 0.0082 * |
Residual | 200.78 | 7 | <0.0001 * | 0.99 | 7 | |||
Lack of Fit | 116.15 | 3 | 1.83 | <0.0001 * | 0.46 | 3 | 1.18 | 0.4221 ** |
Pure Error | 84.63 | 4 | 0.52 | 4 | ||||
Total | 29,628.62 | 16 | 664.10 | 16 |
Samples | Egg | Score | ||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Nonirritant | Mild Irritant | Moderate Irritant | Severe Irritant | Overall Score | ||||||||||||
Time (min) | Time (min) | Time (min) | Time (min) | |||||||||||||
0 | 0.5 | 2 | 5 | 0.5 | 2 | 5 | 0.5 | 2 | 5 | 0 | 0.5 | 2 | 5 | |||
BN-BSog | Egg 1 | 0 | 0 | 0 | 0.0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Egg 2 | 0 | 0 | 0 | 0.0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
Egg 3 | 0 | 0 | 0 | 0.2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
Mean score | 0 | 0 | 0 | 0.2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
Positive control (SLS, 2%) | Egg 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 14 | 17 | 19 | 17.44 |
Egg 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 16 | 18 | 19 | ||
Egg 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 16 | 18 | 20 | ||
Mean score | 0 | 0 | 0 | 0. | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 15.33 | 17.66 | 19.33 | ||
Negative control (NS, 0.9%) | Egg 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Egg 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
Egg 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
Mean score | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Independent Variables | Dependent Variables | |
---|---|---|
Lower (−1) | Upper (+1) | |
Lipid (%) | 1.5 | 4.5 |
Surfactant (Span 60, mg) | 30 | 60 |
Bile salt (mg) | 15 | 25 |
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Zafar, A.; Imam, S.S.; Alruwaili, N.K.; Yasir, M.; Alsaidan, O.A.; Alshehri, S.; Ghoneim, M.M.; Khalid, M.; Alquraini, A.; Alharthi, S.S. Formulation and Evaluation of Topical Nano-Lipid-Based Delivery of Butenafine: In Vitro Characterization and Antifungal Activity. Gels 2022, 8, 133. https://doi.org/10.3390/gels8020133
Zafar A, Imam SS, Alruwaili NK, Yasir M, Alsaidan OA, Alshehri S, Ghoneim MM, Khalid M, Alquraini A, Alharthi SS. Formulation and Evaluation of Topical Nano-Lipid-Based Delivery of Butenafine: In Vitro Characterization and Antifungal Activity. Gels. 2022; 8(2):133. https://doi.org/10.3390/gels8020133
Chicago/Turabian StyleZafar, Ameeduzzafar, Syed Sarim Imam, Nabil K. Alruwaili, Mohd Yasir, Omar Awad Alsaidan, Sultan Alshehri, Mohammed M. Ghoneim, Mohammad Khalid, Ali Alquraini, and Salman S. Alharthi. 2022. "Formulation and Evaluation of Topical Nano-Lipid-Based Delivery of Butenafine: In Vitro Characterization and Antifungal Activity" Gels 8, no. 2: 133. https://doi.org/10.3390/gels8020133