Formulation, Optimization, and Comprehensive Characterization of Topical Essential Oil-Loaded Anti-Acne Microemulgels
Abstract
1. Introduction
2. Results and Discussion
2.1. Physicochemical Characteristics of Essential Oils
2.2. Solubility
2.3. Microbiology Pre-Formulation
2.4. Formulation and Optimization
HLB Values of Different Smix Ratios
2.5. Stability of Microemulsions
2.5.1. Kinetic Stability Findings
2.5.2. Thermodynamic Stability
2.6. Physicochemical Characteristics of Microemulsions
2.7. Microscopy of Microemulsions
2.8. Physicochemical Properties of Microemulgels
2.9. FTIR
2.10. DSC
2.11. Stability Testing of the Formulations
2.12. Antimicrobial Activities of the Microemulgel Formulations
2.13. Discussion
3. Conclusions
4. Materials and Methods
4.1. Materials
4.2. Pre-Formulation
4.2.1. Physicochemical Characterization of Essential Oils
4.2.2. Microbiology Pre-Formulation Studies
- Essential oils
- Strain of Cutibacterium acnes
- Preparation of essential oil working solutions
- Serial dilution of solubilized EOs
4.3. Formulation Optimization
4.3.1. Selection of Components
4.3.2. Determination of HLB Values
4.3.3. Pseudo-Ternary Phase Diagram Construction
4.4. Stability of Emulsion
4.4.1. Kinetic Stability
4.4.2. Thermodynamic Stability Studies
4.5. Preparation of Microemulsion Loaded with Essential Oil
4.6. Physicochemical Properties of Microemulsions
4.6.1. Globule/Droplet Size
4.6.2. Refractive Index
4.6.3. Microemulsions’ Conductivity
4.6.4. Microemulsions’ Viscosity
4.7. Preparation of Emulgel
4.7.1. Preparation of the Gel
4.7.2. Incorporation of the Prepared Gel into Already Prepared Microemulsion
4.7.3. Optimization of the Emulgel Formulation
4.8. Physicochemical Properties of the Microemulgels
4.8.1. Physical Appearance
4.8.2. pH Determination
4.8.3. Microemulgels’ Conductivity
4.8.4. Microemulgels’ Viscosity
4.8.5. Spreadability
4.8.6. Extrudability
4.8.7. FTIR Analysis
4.8.8. Differential Scanning Calorimetry (DSC)
4.8.9. Physical Stability
4.9. Antimicrobial Activities of Microemulgels
4.10. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Essential Oil | Color | Clarity | Form | Odor | Solubility | Density (g/mL) |
---|---|---|---|---|---|---|
C. witerianus | Light yellow | Clear | Liquid | Lemony | + | 0.892 |
M. alternifolia | Colorless | Clear | Liquid | Pungent | + | 0.898 |
C. flexuosus | Golden yellow | Clear | Liquid | Lemony | + | 0.984 |
Essential Oil | MIC (v/v%) | MBC (v/v%) |
---|---|---|
Citronella | 0.078 | 0.125 |
Tea tree | 0.016 | 1.000 |
Lemongrass | 0.062 | 0.25 |
Smix Ratio (PEG-40/Transcutol) | HLB Value |
---|---|
0:1 | 4.20 |
1:1 | 9.60 |
1:2 | 7.76 |
1:3 | 6.90 |
1:4 | 6.36 |
2:1 | 11.45 |
3:1 | 12.30 |
4:1 | 12.84 |
1:0 | 15.00 |
Microemulsion | 1000 rpm | 2000 rpm | 3000 rpm |
---|---|---|---|
AE1 | ✓ | ✓ | X |
AE2 | ✓ | ✓ | ✓ |
AE3 | X | X | X |
AE4 | ✓ | ✓ | X |
Microemulsion | Heating-Cooling | Centrifugation | Freeze–Thaw |
---|---|---|---|
AE1 | ✓ | X | X |
AE2 | ✓ | ✓ | ✓ |
AE3 | X | X | X |
AE4 | X | X | X |
Formulations | E0 | E1 | E2 | E3 | E4 | E5 | E6 | E7 |
---|---|---|---|---|---|---|---|---|
Droplet size + SD (μm) | 4.48 ± 2.59 | 4.74 ± 3.58 | 4.69 ± 2.79 | 8.28 ± 4.72 | 5.44 ± 2.73 | 6.38 ± 3.63 | 6.60 ± 1.98 | 6.77 ± 2.76 |
Refractive index | 1.08 ± 0.12 | 1.07 ± 0.05 | 1.08 ± 0.07 | 1.07 ± 0.11 | 1.08 ± 0.04 | 1.07 ± 0.09 | 1.07 ± 0.14 | 1.07 ± 0.18 |
Conductivity (µS/cm) | 105.3 ± 1.2 | 102.7 ± 2.3 | 106 ± 2.0 | 97.3 ± 2.5 | 103.3 ± 3.1 | 102.0 ± 3.0 | 94.3 ± 3.1 | 105.3 ± 1.2 |
Viscosity (cP) | 22.0 ± 0.92 | 23.0 ± 1.27 | 22.0 ± 1.32 | 23.0 ± 1.59 | 23.0 ± 1.22 | 22.0 ± 1.02 | 23.0 ± 0.82 | 25.0 ± 1.15 |
Formulations | EG0 | EG1 | EG2 | EG3 | EG4 | EG5 | EG6 | EG7 |
---|---|---|---|---|---|---|---|---|
Color | White | White | White | White | White | White | White | White |
Texture | Smooth | Smooth | Smooth | Smooth | Smooth | Smooth | Smooth | Smooth |
Odor | Nutty/earthy | Floral smell | Grassy smell | Citrus /pungent | Citrus /pungent | Grassy /floral | Lemon /pungent | Citrus /pungent |
Homogeneity | Good | Good | Good | Good | Good | Good | Good | Good |
pH | 5.00 ± 0.03 | 4.94 ± 0.12 | 4.93 ± 0.08 | 4.95 ± 0.06 | 4.84 ± 0.14 | 4.94 ± 0.18 | 4.97 ± 0.10 | 4.81 ± 0.08 |
Conductivity (µS/cm) | 843.3 ± 9.2 | 750 ± 32.9 | 749.7 ± 18.2 | 755.3 ± 30.1 | 774.3 ± 12.9 | 754.0 ± 0.0 | 759.3 ± 7.0 | 840.7 ± 5.9 |
Viscosity (cP) | 29.50 ± 0.83 | 30.20 ± 0.66 | 30.80 ± 0.72 | 29.80 ± 0.42 | 30.90 ± 1.04 | 30.50 ± 0.55 | 30.70 ± 0.45 | 31.13 ± 1.25 |
Spreadability (cm2) | 9.8 ± 0.6 | 11.8 ± 0.5 | 11.6 ± 0.8 | 12.1 ± 1.0 | 11.9 ± 1.1 | 12.4 ± 0.6 | 12.1 ± 0.2 | 12.7 ± 0.8 |
Extrudability (g/cm2) | 133.3 ± 3.6 | 142.3 ± 1.8 | 141.3 ± 2.4 | 144.3 ± 1.6 | 148.3 ± 4.3 | 146.3 ± 2.8 | 155.3 ± 4.3 | 166.7 ± 2.3 |
Wavenumber (cm−1) | Functional Groups/Bonds | Vibrational Modes | Likely Sources in Sample | Found In |
---|---|---|---|---|
3740–3650 | O–H (free hydroxyl) | Stretching | Water, phenols in EOs | All analytes, except citronella and EG0 |
3600–3390 | O–H (H-bonded hydroxyl, broad); N–H | Stretching | Carbopol, hyaluronic acid, triethanolamine, water | All analytes, except argan oil and carbopol |
2950–2900 | C–H (CH3, CH2) | Asymmetric/symmetric stretching | Argan oil, citronella, lemongrass, tea tree EOs, aliphatic EO chains, lipid chains, alkane groups | All analytes |
1740–1730 | C=O (ester/carboxylic acid) | Stretching | Argan oil esters, carbopol | Citronella and argan oils |
1690–1620 | C=O (aldehyde, ketone, amide I); C=C (alkene) or amide I | Stretching | Citral in citronella, hyaluronic acid backbone, EO ketones, terpenes (e.g., Limonene), hyaluronic acid | All EGs except EG2 |
1070–1040 | C–O (alcohols, ethers) | Stretching | EO alcohols (geraniol, citronellol), carbopol ester | All analytes except EG0 and EG6 |
1060–1050 | C–O–C (ether)/primary alcohol | Stretching | Argan oil, citronella, lemongrass EOs | EG5, EG4, EG3, carbopol, argan oil |
Week | Color | Homogeneity/Phase Separation | pH | Centrifugation | Viscosity (cP) |
---|---|---|---|---|---|
0 | White | Homogenous | 4.81 ± 0.08 | Stable | 31.13 ± 1.25 |
1 | White | Homogenous | 4.81 ± 0.08 | Stable | 31.90 ± 0.82 |
2 | White | Homogenous | 4.81 ± 0.08 | Stable | 32.22 ± 0.64 |
4 | White | Homogenous | 4.81 ± 0.08 | Stable | 33.93 ± 0.73 |
8 | White | Homogenous | 4.81 ± 0.08 | Stable | 34.02 ± 1.04 |
12 | White | Homogenous | 4.81 ± 0.08 | Stable | 36.42 ± 0.88 |
Week | Color | Homogeneity/Phase Separation | pH | Centrifugation | Viscosity (cP) |
---|---|---|---|---|---|
0 | White | Homogenous | 4.81 ± 0.08 | Stable | 31.13 ± 1.25 |
1 | White | Homogenous | 4.81 ± 0.08 | Stable | 31.45 ± 0.82 |
2 | White | Homogenous | 4.81 ± 0.08 | Stable | 31.62 ± 0.64 |
4 | White | Homogenous | 4.81 ± 0.08 | Stable | 31.93 ± 0.73 |
8 | White | Homogenous | 4.81 ± 0.08 | Stable | 32.02 ± 1.04 |
12 | White | Homogenous | 4.81 ± 0.08 | Stable | 32.42 ± 0.88 |
Week | Color | Homogeneity/Phase Separation | pH | Centrifugation | Viscosity (cP) |
---|---|---|---|---|---|
0 | White | Homogenous | 4.81 ± 0.08 | Stable | 31.13 ± 1.25 |
1 | White | Homogenous | 4.81 ± 0.08 | Stable | 30.96 ± 0.63 |
2 | White | Homogenous | 4.81 ± 0.08 | Stable | 29.42 ± 0.92 |
4 | White | Homogenous | 4.81 ± 0.08 | Stable | 27.58 ± 0.46 |
8 | Off-white | Heterogenous | 4.81 ± 0.08 | Unstable | 24.37 ± 0.78 |
12 | Off-white | Heterogenous | 4.81 ± 0.08 | Unstable | 20.22 ± 0.42 |
Formulation | ZOI (mm) 1% Tween 80 | ZOI (mm) 5% Tween 80 | ZOI (mm) 10% Tween 80 |
---|---|---|---|
EG0 | 6 ± 0 | 6 ± 0 | 6 ± 0 |
EG1 | 6 ± 0 | 6 ± 0 | 6 ± 0 |
EG2 | 15 ± 0 | 15 ± 0 | 15 ± 0 |
EG3 | 15 ± 0 | 20 ± 0 | 25 ± 0 |
EG4 | 20 ± 0 | 23 ± 0 | 25 ± 0 |
EG5 | 15 ± 0 | 23 ± 0 | 25 ± 0 |
EG6 | 20 ± 0 | 20 ± 0 | 20 ± 0 |
EG7 | 20 ± 0 | 20 ± 0 | 20 ± 0 |
Type | Oil (%) | Smix (%) | Water (%) |
---|---|---|---|
AE1 | 5 | 10 | 85 |
AE2 | 10 | 15 | 75 |
AE3 | 15 | 20 | 65 |
AE4 | 20 | 30 | 50 |
Components | G1 (%) | G2 | G3 | G4 | G5 | G6 | G7 |
---|---|---|---|---|---|---|---|
Carbopol 940 | 1.0 | 1.5 | 2.0 | - | 1.0 | 1.5 | 2.0 |
Hyaluronic acid | - | - | - | 1.0 | 1.0 | 1.0 | 1.0 |
Germall™ plus | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 |
Deionized water up to | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 |
Components | Unloaded EG0 (%) | EG1 (%) | EG2 (%) | EG3 (%) | EG4 (%) | EG5 (%) | EG6 (%) | EG7 (%) |
---|---|---|---|---|---|---|---|---|
Citronella essential oil | - | 0.08 | - | - | 0.08 | - | 0.08 | 0.08 |
Tea tree essential oil | - | - | 0.16 | - | 0.16 | 0.16 | - | 0.16 |
Lemongrass essential oil | - | - | - | 0.63 | - | 0.63 | 0.63 | 0.63 |
Argan oil | 10.0 | 9.92 | 9.84 | 9.37 | 9.76 | 9.21 | 9.29 | 9.13 |
Carbopol 940 | 2.0 | 2.0 | 2.0 | 2.0 | 2.0 | 2.0 | 2.0 | 2.0 |
Hyaluronic acid | 1.0 | 1.0 | 1.0 | 1.0 | 1.0 | 1.0 | 1.0 | 1.0 |
Germal plus | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 |
Triethanolamine | qs | qs | qs | qs | qs | qs | qs | qs |
Deionized water up to | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 |
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Kola-Mustapha, A.T.; Raji, M.A.; Alzahrani, Y.A.; Binsaeed, N.H.; Adam, D.R.; Shameh, R.A.; Garaween, N.M.; Garaween, G. Formulation, Optimization, and Comprehensive Characterization of Topical Essential Oil-Loaded Anti-Acne Microemulgels. Gels 2025, 11, 612. https://doi.org/10.3390/gels11080612
Kola-Mustapha AT, Raji MA, Alzahrani YA, Binsaeed NH, Adam DR, Shameh RA, Garaween NM, Garaween G. Formulation, Optimization, and Comprehensive Characterization of Topical Essential Oil-Loaded Anti-Acne Microemulgels. Gels. 2025; 11(8):612. https://doi.org/10.3390/gels11080612
Chicago/Turabian StyleKola-Mustapha, Adeola Tawakalitu, Muhabat Adeola Raji, Yusra Abdulkarim Alzahrani, Noura Hatim Binsaeed, Doaa Rashed Adam, Ranim Abou Shameh, Noureldeen Mohammed Garaween, and Ghada Garaween. 2025. "Formulation, Optimization, and Comprehensive Characterization of Topical Essential Oil-Loaded Anti-Acne Microemulgels" Gels 11, no. 8: 612. https://doi.org/10.3390/gels11080612
APA StyleKola-Mustapha, A. T., Raji, M. A., Alzahrani, Y. A., Binsaeed, N. H., Adam, D. R., Shameh, R. A., Garaween, N. M., & Garaween, G. (2025). Formulation, Optimization, and Comprehensive Characterization of Topical Essential Oil-Loaded Anti-Acne Microemulgels. Gels, 11(8), 612. https://doi.org/10.3390/gels11080612