. 2020 Nov 19;10(11):2292. doi: 10.3390/nano10112292

Table 4.

Valuable results of experimental studies considering anti-acne microemulsion systems.

No.	API ME Type Method	Composition	Observations	Ref.
1.	Tretinoin O/W Water titration method	S1: Tween 80 30% S2: Lecithin 1% CoS: Ethanol 10% Oil: isopropyl myristate (IPM) 5% Water: PBS¹ pH 5.5	Mean particle size: 110 nm. The release (µg/cm²/h): maximum for ME and MEgel compared with other formulations: ME > MEgel > gel > comm. gel > solution 33.92 > 31.54 > 28.67 > 24.28 > 22.33 The retention (g/cm²): greater for MEs, in the following order: MEgel > ME > Solution > comm. gel > gel 96.28 > 82.13 > 32.40 > 29.32 > 21.54.	[231]
2.	Tretinoin 0.05% O/W Water titration method	S1: Tween 80 S2: Labrasol CoS: PG Amount S1/S2CoS: 55–90% IPM + Transcutol P as oil phase: 5–30% Water: 5–15% Km 3:1 and 4:1 ME model: S/CoS 65%/Oil 30%/Water 5%	Mean particle size: 14–60 nm. The pH was situated in the near physiological range: 6.1–6.87. PDI¹ values: 0.352–0.411, defining the homogeneity of the systems. Refractive index variation: 1.4397–1.4505, as a mark of isotropy. The release in 8 h from ME model was 49%.	[285]
3.	Tretinoin O/W Oil titration method	For screening: S: Tween 20, 40, 80, glyceryl stearate, stearyl alcohol, Span 20 or 80 CoS: PG, ethanol, isopropanol, PEG 4000 or PEG 6000 S/CoS amount: 45% Oil: olive oil, castor oil or IPM 10–17% Water: 38–45%	O/W MEs are suitable systems for tretinoin delivery. Span 20 and 80: not preferred for O/W systems. Glyceryl stearate and stearyl alcohol modified the viscosity of the systems. PEG 4000 and 6000 may increase the viscosity due to their high molecular weight. Ethanol and isopropanol may be reconsidered due to their fluidity promotion in ME systems. PG was preferred, along with Tween 80 and olive oil, promoting a maximum release of tretinoin of 82% in 24 h.	[264]
4.	Isotretinoin 0.5% O/W Water titration method	S: Caprylocaproyl macrogol-8-glyceride 31.5% CoS: Polyglyceryl oleate 10.5% Oil: IPM 4.0% Water: q.s. and optimal Km 3:1	Mean particle size (ME model): 45 ± 0.5 nm PDI¹ value (ME model) was 0.145 ± 0.027, defining the homogeneity of the system. Refractive index (ME model): 1.329, as a mark of isotropy.	[288]
5.	Isotretinoin 0.05% O/W or W/O Water titration method	S: Labrasol 24–54% CoS: Plurol oleique 8–18% Oil: IPM 8–18% Water: 10–60%, and optimal Km 3:1 ME model had the following formula: S 24%/CoS 8%/Oil 8%/Water 60% Carbopol 971P NF 2% was added to create a MEgel	Mean particle size: 22.4 ± 0.2 nm (ME model)–85.9 ± 3.7 nm. pH was situated in the near physiological range: 6.30 ± 0.01–6.67 ± 0.06 (ME model). Conductivity values: 2.4 ± 0.1–68.6 ± 0.4 µS/cm, correlated with the amount of water and the type of ME. O/W type: attributed to the ME model. Viscosity for ME model increased from a fluid type (38 ± 0.07 cP) to a high viscosity (6.5 × 103 ± 2 × 103 cP), correlated with the addition of the gelling agent. Skin drug deposition was improved.	[289]
6.	Isotretinoin 0.05% O/W Water titration method	S: Labrasol 26.25–46.80% CoS: Kolliphor HS 7–12.5% or Kolliphor EL 7–12.5% or Plurol oleique 10–14.63% Oil: IPM 3.8–6.5% Water 34.94–61.14% and Km 3:1 and 4:1	Kolliphor EL and HS: promote a diminishing in particle dimension. API embedding did not affect ME’s properties. Conductivity values: 7.50 ± 0.06–77.65 ± 0.21 µS/cm, correlated with the amount of water and the type of ME. Viscosity: 22.15 ± 0.06–88.00 ± 0.19 cP. The Newtonian behaviour of MEs was correlated with MEs fluidity.	[291]
7.	Isotretinoin 0.05% W/O Water titration method	ME model formula: Kolliphor 22.5%/Ethanol 7.5%/Oil 8%/Water 61.95%/API 0.05%, Carbopol ETD 2020 0.75% and TEA ¹ q.s. were added for ME gel	The ME model: used to prepare a ME based spray with isotretinoin and a ME based gel which. Particle size for MEspray: 68.79 nm The release (µg/cm²/h): maximum for MEspray: MEspray > MEgel > commercial gel 27.67 ± 0.12 > 21.81 ± 0.103 > 19.29 ± 0.34.	[292]
8.	Adapalene 0.1% O/W Water titration method	3 MEs types: 1. Plantacare 2000 15.9%/PG 30%/C90 15%/Water 39.1% 2. Plantacare 810 17.8%/PG 28%/C90 14%/Water 40.2% 3. Emanon 28%/Transcutol P 28%/C90 14%/Water 30%	Oil solubility of alkyl polyglucoside can be increased using CoS; Adapalene: good solubility in Plantacare tensioactives and Emanon EV and also in the oil. Adapalene embedding did not affect ME properties. pH values 7.38 ± 0.01–8.49 ± 0.01. Conductivity values: 61.6 ± 0.6 µS/cm (ME with Emanon) and 1022.0 ± 14.0 µS/cm (ME with Plantacare), correlated with the O/W type. Viscosity: 19.6 ± 0.27–27.90 ± 0.32 cP. The Newtonian behaviour of MEs was correlated with MEs fluidity. Skin application: favorable.	[300]
9.	Erythromycin 0.5% W/O Water titration method	S: Tween 20 CoS: PEG 400 Oil: avocado oil and IPM Water: 5–15% and Km 1:1	pH values: 5.02–5.35. Conductivity values: 11.98 ± 1.21–29.39 ± 1.92 µS/cm, correlated with the O/W type. Viscosity: 33.32 ± 1.58–58.50 ± 1.74 mPa·s. The Newtonian behaviour of MEs was correlated with MEs fluidity. PEG 400: implied in hydration and ME spreadability. The release: <40%/6 h (in vitro), influenced by the low water amount of 10%. PEG 400, an elevated water content and the adjusting of oil fraction should be reconsidered.	[305]
10.	Nadifloxacin O/W Water titration method	S: Tween 80 CoS: Transcutol P, with S/CoS 30–60% Oil: C90 10–20% and optimal Km 1:1 Were formulated 2 MEgels, using 1. xanthan gum or 2.Carbopol ETD 2020	Mean particle size: 65 ± 1.35–121.64 ± 1.35 nm. PDI¹ values: 0.890 ± 0.124–1.132 ± 0.006, defining the homogeneity of the systems. S and CoS c% influence the particle dimension and drug entrapment. A high oil content will increase the particle diameter. Highest drug loading: for 10% oil and 60%S/CoS mix. S/CoS mix exerted penetration activity, altering the lipidic structure, assuring the passage of nadifloxacin.	[307]
11.	Azelaic acid O/W Water titration method	S: Tween 80 and Labrasol 60–70% CoS: C90 Oil: oleic acid and Transcutol P (10:1) 5–10% Water: 20–30% Transcutol P was added in the oil phase due to its solubilization power And Km: 6:1 and 4:1	Mean particle size: 48.05 ± 0.75–151 ± 1.1 nm. Viscosity: 72.5 ± 1.45–83 ± 1.7 cP. The Newtonian behaviour of MEs was correlated with MEs fluidity. Release: up to 42% in 24 h.	[309]
12.	Metronidazole 0.75% W/O Water titration method	Optimal ME: S: Lecithin 35.75% CoS: Butanol 17.86% Oil: IPM 26.86% Water: 18.86% and Km 2:1	Mean particle size: 11.6 nm. Conductivity: 1.5µS/cm, correlated with the W/O type. Viscosity: 457.3 mPa·s The Newtonian behaviour of MEs was correlated with MEs fluidity. Stability over 6 months.	[311]
13.	Metronidazole 1% O/W Water titration method	Optimal emulgel: Acconon 16.67% PG 8.33%, Capmul 10%, Preservatives 0.22%, Xanthan gum 1%, TEA ¹ q.s, Water q.s. and Km 2:1	pH values: 6.0–6.9. Viscosity (optimal emulgel): 4568 ± 0.32 mPa·s (at 10 rpm) through 1087 ± 0.43 mPa·s (at 100 rpm). Rheological behaviour: expressed as shear thinning. The release (optimal emulgel): 93.16%.	[312]
14.	Dapsone O/W Water titration method	S: Kolliphor EL CoS: PEG 400, and S/CoS 20–43% Oil: Capryol and N-methyl-2-pyrolidone (1:1) 3–10% Water: 50–70% and Km 1:1, 2:1, 1:2 ME model had the following formula: S/CoS 32%/Oil 6%/Water 62% and Km 1:1	Mean particle size: 27.53 (ME model)–64.40 nm. pH: 5.6–6 (ME model); Conductivity: 13–15.8 µS/cm, correlated with the O/W type. Drug entrapment for ME model: 97.99 ± 0.040%. The release: 70 ± 0.09%.	[313]
15.	Dapsone 5.15% O/W Water titration method	For optimal ME: S: Tween 80 18% CoS: Transcutol P 20% and ethanol 18% Oil: IPM 4% Water: 34.85% Two ME models derived from the first optimal: by adding menthol 2.5–5% Carbomer 940 0.5% was added.	Mean particle size (ME without menthol): 48.3 nm; Menthol has increased the particle size due to its hydrophobicity, being localized at the interface. pH values: 5.46–5.50. Conductivity: 25.40–28.25 µS/cm, correlated with the O/W type. Permeation values for MEgel: 74.38 ± 0.70–106.25 ± 4.84 µg/cm²/10 h. Stability over 6 months.	[314]

¹ Abbreviations: PBS—Phosphate buffer saline, PDI—polydispersity index, TEA—triethanolamine.