Mometasone furoate-loaded cold processed oil-in-water emulsions:in vitroandin vivostudies

Abstract

Over the years, research has focused on strategies to increase benefit/risk ratio of corticoids. However, vehicles intended for topical glucocorticoids delivery with an improved benefit/risk ratio are still on demand. The aim of this work was the in vitro and in vivo characterization of cold processed oil-in-water (o/w) emulsions intended for mometasone furoate (MF) delivery to induce drug targeting to upper skin strata, decreasing adverse effects. Two o/w emulsions, containing 0.1% of MF, were developed differing in the glycol used (2-methyl-2,4-pentanediol -PT and ethoxydiglycol -TC emulsions). In vitro permeation studies revealed that these emulsions are suitable vehicles for the delivery of MF containing ingredients which are responsible for a drastically increased on the permeability coefficients of MF from a theoretical value of 1.18 Â 10 À4 cm/h to 5.20 Â 10 À4 AE 2.05 Â 10 À4 cm/h and 6.30 Â 10 À4 AE 2.94 Â 10 À4 cm/h, for PT and TC, respectively. The tape stripping results showed that the amount of drug that reached the viable skin layers was very low (1.99 %) and the amount that remained in the stratum corneum (SC) was 10.61%. The in vivo studies showed that the developed formulations decreased the edema and erythema in mice skin in more that 90%, assuring, at least, the same anti-inflammatory effect compared with the commercial cream. PT placebo demonstrated to contribute to restore the skin barrier by increasing the amount of lipids within the human skin.

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“…could be useful in the treatment of skin inflammatory diseases. [57][58][59] Histopathological Evaluation Compared with the skin from normal control mice group ( Figure 10A), histopathological examination of mice skin tissues exposed to croton oil alone revealed epidermal damage, dermal congestion and edema in addition to marked inflammatory cells infiltration mainly polymorphonuclear (PMN) leukocytes in epidermis and dermis ( Figure 10B). Once topical treatment with CEO alone, CEO-NE-based NEG or plain-NE-based NFs did not significantly reduce the harmful effect of croton oil on the skin where the separation of the epidermis from the basement membrane, PMN cells aggregation in epidermis and dermis with dermal congestion and edema were observed ( Figure 10C, D and G).…”

Ex vivo Cutaneous Bioavailability of Topical Mometasone Furoate in an O/W Preparation

“…Thus, no relevant clinical symptoms caused by adverse cutaneous effects are to be expected, at least for short- and medium-term use. This was also proven by the currently available safety data from clinical studies [21,24]. …”

“…This includes both, the range of concentration-dependent adverse cutaneous effects as well as the potential systemic bioavailability [52]. The detectable concentrations of MMF in the vital epidermis (about 100 µmol/L) and in the dermis (about 20 µmol/L) were within a cutaneous toxicologically harmless dose range [21]. However, the current evidence for cutaneous toxicological effects is quite low, and whether the toxicological data from MMF inhalation can be directly transferred remains doubtful.…”

“…MMF is classified by Niedner [18,19] as a highly potent glucocorticoid (class III out of IV). The duration of application and the galenic properties of the vehicle have a major influence on the therapeutic effect [20,21,22,23]. The efficacy of MMF as a topical treatment has been proven for a variety of inflammatory dermatoses [24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40].…”

“…In order to make better use of the intrinsic effect of the vehicle, especially in periods of acute inflammation, an MMF-containing O/W vehicle has recently been created, whose efficacy can be compared to conventional W/O cream or ointment preparations [21,24]. With regard to a continuous long-term application especially on damaged skin, the concentration-time profile of MMF in the different skin layers is of vital importance not only for its therapeutic effect but also for the severity of its adverse reactions.…”