Figure 1.
Figure 2.
Figure 3.
Figure 4.
Figure 5.
Figure 6.
Figure 7.
Coefficient of determination (R2) values for different kinetic models for the optimized flucytosine nanoemulsion formulation (F7)
| Kinetic Model | Coefficient of determination (R2) |
|---|---|
| Zero Order | 0.8977 |
| Frist Order | 0.9978 |
| Higuchi Model | 0.9898 |
| Korsmeyer-Peppas | 0.9786 |
Antifungal Activity of Flucytosine Nanoemulsion by Zone of Inhibition
| Sample | Zone of Inhibition (mm) |
|---|---|
| Flucytosine Solution | 14.2 ± 0.8 |
| Flucytosine Nanoemulsion (F7) | 22.6 ± 1.1 |
| Blank Nanoemulsion | No zone |
| Standard Antifungal (Fluconazole) | 24.1 ± 0.9 |
Characterization Parameters of Flucytosine Nanoemulsions
| Formulation | Zeta Potential (mV) | pH | Drug Content |
|---|---|---|---|
| F1 | −14.2 ± 1.3 | 6.41 ± 0.04 | 91.2 ± 1.5 |
| F2 | −16.1 ± 1.4 | 6.46 ± 0.03 | 92.6 ± 1.4 |
| F3 | −17.8 ± 1.2 | 6.52 ± 0.02 | 93.8 ± 1.3 |
| F4 | −19.6 ± 1.3 | 6.58 ± 0.03 | 95.1 ± 1.2 |
| F5 | −21.4 ± 1.1 | 6.63 ± 0.02 | 96.4 ± 1.1 |
| F6 | −23.1 ± 1.4 | 6.69 ± 0.03 | 97.6 ± 1.0 |
| F7 | −27.6 ± 1.2 | 6.75 ± 0.02 | 98.5 ± 0.8 |
| F8 | −29.1 ± 1.3 | 6.82 ± 0.03 | 97.0 ± 0.7 |
| F9 | −31.5 ± 1.1 | 6.88 ± 0.02 | 96.3 ± 0.6 |
Variables in Box–Behnken design
| Factor Independent variables | Levels used | ||
|---|---|---|---|
| −1 | 0 | +1 | |
| Amount of oil (mL) (X1) | 5 | 10 | 15 |
| Smix (X2) | 1.0 | 1.5 | 2.0 |
| Homogenization Time (min) (X3) | 20 | 25 | 30 |
| Dependent variables | Constraints | ||
| Particle size (nm) (Y1) | Minimize | ||
| PDI (Y2) | Minimize | ||
| Entrapment Efficiency (%) (Y3) | Maximize | ||
Composition and observed responses in Box–Behnken design
| Batch | Drug (mg) | Independent Variables | Dependent variables | ||||
|---|---|---|---|---|---|---|---|
| A: Amount of Oil (ml) (X1) | Smix (X2) | Homogenization Time (min) (X3) | Particle Size (nm) | PDI | %EE | ||
| 1 | 100 | 5 | 1.5 | 30 | 269 | 0.141 | 79.81 |
| 2 | 100 | 10 | 1 | 30 | 224 | 0.106 | 96.01 |
| 3 | 100 | 5 | 1.5 | 20 | 278 | 0.133 | 71.12 |
| 4 | 100 | 10 | 1.5 | 25 | 229 | 0.112 | 85.89 |
| 5 | 100 | 5 | 2 | 25 | 257 | 0.148 | 71.89 |
| 6 | 100 | 5 | 1 | 25 | 271 | 0.141 | 72.45 |
| 7 | 100 | 15 | 1 | 25 | 202 | 0.117 | 84.31 |
| 8 | 100 | 15 | 1.5 | 20 | 203 | 0.105 | 86.93 |
| 9 | 100 | 15 | 2 | 25 | 197 | 0.116 | 89.18 |
| 10 | 100 | 10 | 1 | 20 | 219 | 0.119 | 91.43 |
| 11 | 100 | 10 | 2 | 30 | 218 | 0.121 | 92.87 |
| 12 | 100 | 10 | 1.5 | 25 | 215 | 0.112 | 82.16 |
| 13 | 100 | 15 | 1.5 | 30 | 198 | 0.109 | 84.57 |
| 14 | 100 | 10 | 2 | 20 | 211 | 0.104 | 90.79 |
| 15 | 100 | 10 | 1.5 | 25 | 222 | 0.115 | 87.11 |
| 16 | 100 | 10 | 1.5 | 25 | 217 | 0.111 | 84.94 |
| 17 | 100 | 10 | 1.5 | 25 | 212 | 0.11 | 86.91 |
Stability studies result of optimized formulation (F7)
| Storage Condition | Time (Months) | Appearance | Particle Size (nm) | PDI | Zeta Potential (mV) | pH | % EE | Drug Content (%) |
|---|---|---|---|---|---|---|---|---|
| Initial | 0 | Clear, homogeneous | 104.3 ± 1.9 | 0.15 ± 0.01 | −27.6 ± 1.2 | 6.75 ± 0.02 | 94.8 ± 1.1 | 98.5 ± 0.8 |
| 4 ± 2 °C | 1 | No change | 105.1 ± 2.1 | 0.16 ± 0.01 | −27.2 ± 1.3 | 6.74 ± 0.03 | 94.2 ± 1.2 | 98.1 ± 0.9 |
| 2 | No change | 106.4 ± 2.3 | 0.17 ± 0.02 | −26.9 ± 1.4 | 6.73 ± 0.03 | 93.6 ± 1.4 | 97.8 ± 1.0 | |
| 3 | No change | 107.2 ± 2.5 | 0.18 ± 0.02 | −26.5 ± 1.5 | 6.72 ± 0.04 | 92.9 ± 1.6 | 97.4 ± 1.1 | |
| 25 ± 2 °C / 60 ± 5% RH | 1 | No change | 106.3 ± 2.4 | 0.17 ± 0.01 | −26.8 ± 1.3 | 6.73 ± 0.03 | 93.8 ± 1.3 | 97.9 ± 0.9 |
| 2 | No change | 108.5 ± 2.6 | 0.18 ± 0.02 | −26.2 ± 1.4 | 6.71 ± 0.04 | 92.7 ± 1.5 | 97.2 ± 1.1 | |
| 3 | No change | 110.2 ± 2.9 | 0.19 ± 0.02 | −25.6 ± 1.6 | 6.69 ± 0.05 | 91.8 ± 1.7 | 96.6 ± 1.2 | |
| 40 ± 2 °C / 75 ± 5% RH | 1 | No change | 109.6 ± 2.8 | 0.19 ± 0.02 | −25.9 ± 1.4 | 6.70 ± 0.04 | 92.4 ± 1.6 | 96.9 ± 1.2 |
| 2 | Slight turbidity | 112.8 ± 3.1 | 0.21 ± 0.02 | −25.1 ± 1.6 | 6.68 ± 0.05 | 91.2 ± 1.8 | 96.1 ± 1.3 | |
| 3 | Slight turbidity | 116.5 ± 3.4 | 0.23 ± 0.03 | −24.3 ± 1.7 | 6.65 ± 0.06 | 89.7 ± 2.0 | 95.4 ± 1.5 |