Quality by Design-Optimized Glycerosome-Enabled Nanosunscreen Gel of Rutin Hydrate
Abstract
:1. Introduction
2. Results and Discussion
2.1. Using the Quality by Design Method to Develop a Robust Formulation
2.2. Model Fitting and Optimization Using Box Behnken Design
2.3. Optimization of RUT-Loaded GM by Statistical Design
2.3.1. Analysis of Response Surfaces
Impact of Independent Factor on Vesicle Size (Y1)
Influence of Independent Factor on PDI
Influence of Independent Factor on EE%
2.3.2. Experimental Design Validation
2.3.3. Optimized Level of Formulation by Point Prediction
2.4. Characterization of Opt-RUT-Loaded-GMs
2.4.1. Determination of Vesicles Size, PDI, Zeta Potential and EE%
2.4.2. Determination of Entrapment Efficiency
2.4.3. Morphological Evaluation
2.4.4. Differential Scanning Calorimetry
2.4.5. Compatibility Study Using Fourier Transform Infrared
2.4.6. Powder X-ray Diffraction Analysis
2.4.7. Antioxidant Analysis by 2,2-Diphenyl-1-picrylhydrazyl Assay Method
2.5. Characterization of Opt-RUT-Loaded-GMs Gel
2.6. In Vitro Drug Release Study
2.7. Sun Protection Factor (SPF) Evaluation
2.8. Confocal Laser Scanning Microscopy
2.9. Ex Vivo Dermatokinetic Study
2.10. Skin Irritation Study
2.11. Accelerated Predictive Stability Study
3. Conclusions
4. Material and Methods
4.1. Materials
4.2. Methods
4.2.1. Quality by Design (QbD) Identification of Component
4.2.2. Preparation of RUT-Glycerosomes (RUT-GMs)
4.2.3. Optimization of RUT-Loaded-GMs
4.2.4. Characterization of Opt-RUT-Loaded-GMs
Vesicle Size, PDI and Zeta Potential
Entrapment Efficiency
Differential Scanning Calorimetery
Fourier Transform Infrared Compatibility Study
X-ray Diffraction
Surface Morphology of Opt-RUT-Loaded-GMs
Determination of Antioxidant Activity by 2,2-Diphenyl-1-picrylhydrazyl Assay
4.2.5. Preparation of Opt-RUT-Loaded-GMs Carbopol® Gel
4.2.6. Characterization of Opt-RUT-Loaded-GMs Gel
pH Evaluation
Homogeneity and Viscosity
Spreadability
Extrudability
Texture Analysis
4.2.7. In Vitro Release
4.2.8. Sun Protection Factor Value Determination
- SPF = CF × (λ) × I (λ) × absorbance (λ)
- CF = Correction factor (10)
- EE = Erythmogenic effect of radiation with wavelength λ
- I = Solar Ray Simulation Spectrum
- Abs = spectrophotometric absorbance values at wavelength λ.
4.2.9. Confocal Laser Scanning Microscopy
4.2.10. Ex Vivo Dermatokinetics
4.2.11. In Vivo Study
Skin Irritation Study
4.2.12. Accelerated Stability Study According to ICH Q1A (R2) Guidelines
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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QTPP | Target | Justification |
---|---|---|
Drug delivery system | Glycerosome | Improved skin permeability is preferred by glycerosomes. |
Release type | Sustained release | Slow drug release is necessary to ensure sufficient drug concentration for proper sunburn action. |
Route of administration | Topical | In comparison to oral treatment, it provides localized action with minimum systemic side effects. |
Dosage form | Hydrogel | Provides easier topical application and improved penetration through the skin |
Appearance | white gel with a smooth texture | It is free from gritty particles; the gel is uniformly smooth as well as odorless and Colorless. |
Stability | >3 months | Maintains the therapeutic efficacy of the formulation. |
CQAs | Target | Justification |
Phospholipid 90G | Optimal vesicle size | Phospholipid 90G is a complex of phospholipids that contributes to the development of the phospholipid bilayer and also affects the size of the vesicles. [5] |
Cholesterol | Fluidity and rigidity | Influence of Cholesterol on vesicle size and membrane fluidity. The formation of the phospholipid bilayer involves these components. [6] |
Glycerol | Greater flexibility | The glycerol in these vesicles increases the deformability index, resulting in improved therapeutic skin penetration and permeability. [7] |
Hydration media | Optimal glycerosome stability (absence of aggregation) | The lipid film is hydrated as part of the process of creating the phospholipid bilayer. [8] |
API | The lipophilic API has been successfully incorporated into the glycerosomal wall. | The size of the vesicles may change depending on the nature of API included in the glycerosomes product [5]. |
Particle size | Less than 300 nm | To demonstrate enhanced drug penetration at the targeted skin layers with controlled drug release pattern. |
Polydispersity index | Less than 0.5 | Better homogeneity will result in more effective drug entrapment and release. |
Entrapment Efficiency | More than 80% | Ensures high drug loading, and improved therapeutic results. |
Rutin Conventional Gel | Opt-RUT-Loaded-GMs Gel | |||
---|---|---|---|---|
Dermatokinetic Parameters | Epidermis | Dermis | Epidermis | Dermis |
TSkin max (h) | 2 | 1.5 | 2 | 2 |
CSkin max (µg/cm2) | 64.8814 | 32.4635 | 118.302 | 52.7329 |
AUC0–8 (µg/cm2 h) | 248.3277 | 116.900 | 438.7941 | 197.4062 |
Ke (h−1) | 0.15524 | 0.145283 | 0.129488 | 0.143148 |
Rats | Negative Control | Positive Control | RUT-Loaded-GM Gel | |||
---|---|---|---|---|---|---|
S no. | Erythema | Edema | Erythema | Edema | Erythema | Edema |
1 | 0 | 0 | 2 | 1 | 0 | 0 |
2 | 0 | 0 | 2 | 1 | 0 | 0 |
3 | 0 | 0 | 3 | 2 | 1 | 0 |
- | 0 | 0 | 2.33 ± 0.57 | 1.33 ± 0.57 | 0.33 ± 0.57 | 0 |
Storage Time | Appearance | Separation | pH ± SD | Vesicle Size (nm ± SD) | EE (% ±SD) | PDI (±SD) |
---|---|---|---|---|---|---|
Storage condition (40 °C ± 2 °C) | ||||||
0 day | Clear | No | 5.7 ± 0.1 | 148.067 ± 0.75 | 83.25 ± 0.31 | 0.290 ± 0.004 |
1 week | Clear | No | 5.63 ± 0.20 | 150.36 ± 1.33 | 84.14 ± 0.88 | 0.29 ± 0.001 |
2 weeks | Clear | No | 5.94 ± 0.17 | 156.4 ± 0.79 | 83.34 ± 0.26 | 0.32 ± 0.01 |
1 month | Clear | No | 5.99 ± 0.11 | 163.67 ± 1.86 | 82.14 ± 0.54 | 0.319± 0.003 |
2 months | Turbid | No | 6.26 ± 0.06 | 172.8 ± 1.11 | 80.82 ± 0.7 | 0.382 ± 0.064 |
3 months | Turbid | Yes | 6.39 ± 0.13 | 184.1 ± 1.014 | 79.17 ± 0.36 | 0.35 ± 0.008 |
Storage condition (40 ± 2 °C/75 ± 5% RH) | ||||||
0 day | Clear | No | 5.76 ± 0.152 | 147.22 ± 1.03 | 82.90 ± 0.655 | 0.289 ± 0.004 |
1 week | Clear | No | 5.69 ± 0.10 | 155.64 ± 0.89 | 81.24 ± 1.009 | 0.362 ± 0.014 |
2 weeks | Clear | No | 6.16 ± 0.254 | 166.62 ± 0.79 | 81.82 ± 0.796 | 0.389 ± 0.009 |
1 month | Turbid | Yes | 6.49 ± 0.26 | 188.51 ± 0.89 | 78.58 ± 0.94 | 0.45 ± 0.01 |
2 months | Milky | Yes | 6.39 ± 0.142 | 226.33 ± 2.28 | 73.54 ± 1.36 | 0.55 ± 0.01 |
3 months | Milky | Yes | 6.56 ± 0.210 | 251.26 ± 2.31 | 69.06 ± 0.448 | 0.64 ± 0.012 |
Evaluation Parameters | Initial | 1 month | 3 months | |||
4 ± 2 °C | 40 ± 2 °C/75 ± 5% RH | 4 ± 2 °C | 40 ± 2 °C/75 ± 5% RH | |||
Color | Whitish | Whitish | Whitish | Whitish | Whitish | |
Appearance | Translucent | Translucent | Translucent | Translucent | Translucent | |
Phase Separation | None | None | None | None | None | |
Clarity | *** | *** | *** | *** | ** | |
pH | 5.65 ± 0.28 | 5.71 ± 0.16 | 5.8 ± 0.34 | 5.73 ± 0.12 | 5.87 ± 0.43 | |
Homogeneity | *** | *** | *** | *** | *** | |
Washability | Washable | Washable | Washable | Washable | Washable | |
Odor | None | None | None | None | None |
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Alam, M.S.; Sultana, N.; Rashid, M.A.; Alhamhoom, Y.; Ali, A.; Waheed, A.; Ansari, M.S.; Aqil, M.; Mujeeb, M. Quality by Design-Optimized Glycerosome-Enabled Nanosunscreen Gel of Rutin Hydrate. Gels 2023, 9, 752. https://doi.org/10.3390/gels9090752
Alam MS, Sultana N, Rashid MA, Alhamhoom Y, Ali A, Waheed A, Ansari MS, Aqil M, Mujeeb M. Quality by Design-Optimized Glycerosome-Enabled Nanosunscreen Gel of Rutin Hydrate. Gels. 2023; 9(9):752. https://doi.org/10.3390/gels9090752
Chicago/Turabian StyleAlam, Md. Shabbir, Niha Sultana, Md. Abdur Rashid, Yahya Alhamhoom, Asad Ali, Ayesha Waheed, Mo. Suheb Ansari, Mohd. Aqil, and Mohd Mujeeb. 2023. "Quality by Design-Optimized Glycerosome-Enabled Nanosunscreen Gel of Rutin Hydrate" Gels 9, no. 9: 752. https://doi.org/10.3390/gels9090752