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. 2024 Jun 19;17(6):803.
doi: 10.3390/ph17060803.

Development and Optimization of Dipyridamole- and Roflumilast-Loaded Nanoemulsion and Nanoemulgel for Enhanced Skin Permeation: Formulation, Characterization, and In Vitro Assessment

Zeyad Khalaf Maded  1 , Souad Sfar  2 , Ghada Abd Alrhman Taqa  3 , Mohamed Ali Lassoued  1 , Olfa Ben Hadj Ayed  1 , Hayder Adnan Fawzi  4
Affiliations

Development and Optimization of Dipyridamole- and Roflumilast-Loaded Nanoemulsion and Nanoemulgel for Enhanced Skin Permeation: Formulation, Characterization, and In Vitro Assessment

Zeyad Khalaf Maded et al. Pharmaceuticals (Basel). .

Abstract

This study explores developing and optimizing a nanoemulsion (NE) system loaded with dipyridamole and roflumilast, aiming to improve skin penetration and retention. The NE formulation was further transformed into a nanoemulgel to enhance its application as a topical treatment for psoriasis. Solubility studies were conducted to select the oil, surfactant, and co-surfactant. Phase diagrams were constructed using the aqueous phase titration method. All the formulations were in nanoscale, and Formula (F2) (which contains oleic acid oil as the oil phase, a mixture of Surfactant Tween 80 and co-surfactant (ethanol) at a ratio of 1:2 in addition to distilled water as an aqueous phase in a ratio of 1:5:4, respectively) was the selected formula depending on the particle size, PDI, and zeta potential. Formula (F2) has the best ratio because it gives the smallest nanoemulsion globule size (particle size average of 167.1 nm), the best homogenicity (lowest PDI of 0.195), and the highest stability (higher zeta potential of -32.22). The selected formula was converted into a nanoemulgel by the addition of 0.5% (w/w) xanthan gum (average particle size of 172.7 nm) and the best homogenicity (lowest PDI of 0.121%) and highest stability (higher zeta potential of -28.31). In conclusion, the selected formula has accepted physical and chemical properties, which enhanced skin penetration.

Keywords: Franz cell diffusion; dipyridamole; nanoemulgel; nanoemulsion; psoriasis; roflumilast.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Concentration of dipyridamole (μg/mL), (ppm) in oils, surfactant, and co-surfactant.
Figure 2
Figure 2
Concentration of roflumilast (μg/mL)–(ppm) in oils, surfactant, and co-surfactant.
Figure 3
Figure 3
Concentration of dipyridamole and roflumilast combination (μg/mL)–(ppm) in oils, surfactant, and co-surfactant; (A) dipyridamole and (B) roflumilast.
Figure 4
Figure 4
FTIR spectra of (A) pure dipyridamole, (B) pure roflumilast, (C) dipyridamole—roflumilast, (D) dipyridamole—roflumilast with oleic acid.
Figure 5
Figure 5
The pseudoternary phase diagrams depict the phase diagram for a mixture of oleic oil, Tween 80, and ethanol. (A) Formula (G1) with 1 (Tween 80):2 (ethanol) (Smix) and oleic oil and distilled water, (B) Formula (G2) with 1 (Tween 80):1 (ethanol) (Smix) and oleic oil and distilled water, (C) Formula (G3) with 2 (Tween 80):1 (ethanol) (Smix) and oleic oil and distilled water.
Figure 6
Figure 6
Phase diagram of Formula (F2) for a mixture of oleic oil, Tween 80, and ethanol (in a ratio of 1:2) along with distilled water.
Figure 7
Figure 7
The particle size, PDI, and zeta potential of the nanoemulgel formula (phase diagram (1:2)).
Figure 8
Figure 8
Viscosity values of formula at different shear stress (optimized formula versus F1 gel formula).
Figure 9
Figure 9
Permeability study of (A) pure roflumilast and dipyridamole and (B) nanogel roflumilast and dipyridamole.
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