Ointment containing spray freeze-dried metronidazole effective against rosacea

• Published in: Journal of drug delivery science and technology Vol. 74; p. 103559
• Main Authors: Szentmihályi, Klára, Móricz, Krisztina, Gigler, Gábor, May, Zoltán, Bódis, Eszter, Tóth, Judit, Bakonyi, Mónika, Klébert, Szilvia, Feczkó, Tivadar, Károly, Zoltán
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.08.2022
• Subjects: Metronidazole; Mouse; Oedema; Particle size; Rosacea; Spray freeze-drying; Particle size; Oedema; Spray freeze-drying; XRD; SFD; MTZ; Mouse; rMTZ; ROS; o SFD-MTZ; c rMTZ; SEM; Metronidazole; SFD-MTZ; TEM; Rosacea
• ISSN: 1773-2247
• DOI: 10.1016/j.jddst.2022.103559

Rosacea is a chronic, inflammatory skin disease that affects about 10% of the population. Metronidazole-containing ointments are typically recommended for the daily treatment of symptoms. For increasing bioavailability and effectiveness, it is needed to reduce the particle size. Therefore, micronized metronidazole was prepared by spray freeze-drying (SFD) method, then its most important features were examined such as morphology, crystallinity and particle size. The anti-inflammatory effect of the as-prepared agent was tested on a mouse model of rosacea for effectiveness against oedema and redness of the ears, and it was compared to a reference cream. Metronidazole size was reduced successfully by SFD to 2.7 μm from 162.6 μm. The material was non-porous and preserved its crystalline state. The spray freeze-dried metronidazole mixed into ointment was effective against oedema and ear-redness. The ointment reduced oedema in five times lower doses (2 × 0.04 mg metronidazole) and the ear-redness in half dose (2 × 0.2 mg metronidazole) than the cream containing reference metronidazole (2 × 0.2 mg and 2 × 0.4 mg metronidazole, respectively). In conclusion, the SFD technique is an adequate and gentle procedure for reducing the size of metronidazole, which is highly effective in rosacea. [Display omitted] •Crystalline metronidazole was prepared by spray freeze-drying.•The particle size was reduced to 2.7 μm from 162.6 μm.•The ointment containing the product was effective in 5 times lower doses against oedema.•The ointment containing the product was effective in a half dose in ear-redness.