Mometasone furoate-loaded cold processed oil-in-water emulsions: in vitro and in vivo studies

Figures & data

Table 1. Qualitative and quantitative composition of the developed emulsions.

		Concentration (% w/w)
	Excipients	PT	TC	PT placebo
Oil phase	Bis-PEG/PPG-16/16 PEG/PPG-16/16-dimethicone (and) caprylic/capric triglyceride	5	5	5
	PEG-20 glyceryl laurate	4	4	4
	C12-15 alkyl benzoate	5	5	5
	Isopropyl myristate	5	5	5
Water phase	HPMC^a	2	2	2
	PVM/MA^b	0.3	0.3	0.3
	Cetrimide	0.075	0.075	0.075
	Pentanediol	10	–	10
	Ethoxydiglycol	–	10	–
	MF^c	0.1	0.1	–
	Water	68.625	68.625	68.725

^aHidroxy propyl methyl cellulose.

^bMethyl vinyl ether/maleic anhydride copolymer cross-linked with decadiene.

^cMometasone furoate.

Figure 1. Co-solvent solubility plot of MF in (a) pentanediol–water mixtures and (b) ethoxydiglycol–water mixtures at 22 °C. Measurements were performed at least in duplicate (mean ± SD).

Table 2. Stability test results for PT and TC emulsions during 60 d at 25 °C (n = 3; mean ± SD).

	PT		TC
Time (days)^a	pH	Amount of drug (%)	pH	Amount of drug (%)
0	3.97 ± 0.01	100.9 ± 0.68	3.89 ± 0.01	99.87 ± 0.41
7	3.98 ± 0.02	96.71 ± 0.32	3.87 ± 0.01	97.51 ± 1.51
30	3.99 ± 0.01	97.5 ± 2.35	3.91 ± 0.02	102.2 ± 1.50
60	3.98 ± 0.01	97.66 ± 0.34	3.98 ± 0.01	97.74 ± 0.29

^aAt 25 °C and 60% relative humidity.

Figure 2. Release profile of MF from PT and TC emulsions through Tuffryn® membrane (mean ± SD, n = 6).

Figure 3. Permeation profile of MF from PT and TC through human skin (mean ± SD, n = 6).

Table 3. Kinetic parameters obtained after fitting the release data from the formulations to different release models.

	Zero order			Higushi
	K	b	R^2	k	b	R^2
PT	6.95	1.23	0.994	17.36	−4.79	0.939
TC	6.02	1.49	0.991	15.14	−3.87	0.948

K is the release rate constant, b is the intercept, and R² the coefficient of determination.

Table 4. Flux, permeability coefficient (K_p) and lag time of MF through skin membrane (mean ± SD; n = 6) for PT and TC formulations.

Formulation	Flux (µg/cm^2/h)	Kp (cm/h)	Lag time
PT	0.14 ± 0.055	5.20 × 10^−4 ± 2.05 × 10^−4	7.31 ± 1.36
TC	0.15 ± 0.056	6.30 × 10^−4 ± 2.94 × 10^−4	8.55 ± 0.30

Figure 4. Penetration of MF in the SC and viable skin layers (epidermis and dermis) after 24 h.

Figure 5. Effect of treatment with PT, TC, and MF commercial cream on edema of a mouse croton oil-induced ear inflammation model (mean ± SD, n = 3).

Figure 6. Effect of MF on croton oil-induced inflammatory cell infiltration of mouse ear. H&E-stained histological sections were prepared from ears resected 16 h after challenge: (a) unchallenged ear, (b) ear from mouse challenged with croton-oil in the absence of any treatment, (c) ear from mouse challenged with croton-oil post-treated with PT emulsion, and (d) ear from mouse challenged with croton-oil post-treated with commercial cream. Magnification: 40×.

Table 5. Cell viability in NIH 3T3 and HaCaT cell lines after 72 h of incubation with PT and TC emulsions and MF solubilized in ethoxydiglycol and pentandiol (mean ± SD; n = 6).

	Cell viability (%)
	MF conc (g/mL)	NIH 3T3	HaCat
PT emulsion	5.1 × 10^−6	96.5 ± 3.6	98.3 ± 1.4
TC emulsion		96.7 ± 11.6	104.7 ± 2.3
MF + PT		19.5 ± 3.2	46.20 ± 18.2
MF + TC		19.6 ± 2.7	48.2 ± 17.6

Figure 7. Comparison of skin hydration values in terms of capacitance during 21 d between PT placebo (black bars) and control (gray bars) (mean ± SD, n = 10).

Figure 8. Effect of the application of PT placebo on the skin surface lipids. PT placebo (black bars) and control (gray bars) (mean ± SD, n = 10).