Low drug load, high retention mometasone furoate cream with Polyglyceryl – 3 oleate as a chemical enhancer: formulation development, in vivo and in vitro evaluation and molecular mechanisms

In the present study, an oil-in-water (O/W) cream containing 0.05% mometasone furoate (MF) was prepared for the treatment of atopic dermatitis (AD) using Polyglyceryl-3 oleate (POCC) as a chemical enhancer. The cream formulation was screened by stability and in vitro skin retention studies and optimized by Box-Behnken design. Appearance, rheological and irritation were investigated. The formulations were evaluated by in vivo tissue distribution and pharmacodynamic experiments. The molecular mechanisms by which POCC increases MF release and skin retention were investigated using rheology, molecular simulation, tape stripping, CLSM, ATR-FTIR and SAXS. The optimized formulation contained 10% POCC. Its addition made the cream smoother, more fluid and non-irritating. It increased MF release by 1.77-fold and skin retention in vivo by 3.14-fold. It demonstrated a good therapeutic effect in a mouse model of chronic AD, with a 59.52% reduction in ear weight difference, with no significant difference compared to a commercial cream (Elocon^®) with 0.1% MF. The incorporation of POCC decreased the cohesive energy density of the oil phase of the cream and increased the fluidity of the drug in the cream, which increased the release of MF. It disrupts the long-period phase of lipids in the stratum corneum of the skin and facilitates the entry of MF into the skin, while POCC forms hydrogen bonds with MF and collagen in the dermis, thereby increasing the retention time. This study demonstrated that POCC can be used as a chemical enhancer in creams, providing a reference for the development of semi-solid formulations.

2.1. Materials and animals

Mometasone furoate (MF), Isopropyl palmitate (IPP), Isopropyl myristate (IPM), 2,4-dinitrofluorobenzene (DNFB) were purchased from Shanghai Macklin Biochemical Co., Ltd. (Shanghai, China). N-methyl-2-pyrrolidone (NMP), Oleinic acid (OA) was purchased from Alfa Aesar (MA, USA). Maisine® CC, Labrafac™ lipophile WL 1349(LWL1349), Gelot™ 64, Labrafil®M1944CS (LM1944), Plurol®Oleique CC 497 (Polyglyceryl-3 oleate, POCC), Transcutol®P (TP), Lauroglycol®FCC (FCC) were purchased from GATTEFOSSé (Shanghai, China);HPLC grade methanol was purchased from Tianjin Concord technology Co., Ltd. (Tianjin, China); All of the reagents used in the cream were of reagent grade and obtained commercially.

Download the full study preprint as PDF here: Low drug load, high retention mometasone furoate cream with Polyglyceryl – 3 oleate as a chemical enhancer: formulation development, in vivo and in vitro evaluation and molecular mechanisms

or read it here

Wenxuan Jia, Yu Pang, Chenyu Zhao et al. Low drug load，high retention mometasone furoate cream with Polyglyceryl – 3 oleate as a chemical enhancer: formulation development, in vivo and in vitro evaluation and molecular mechanisms, 11 October 2023, PREPRINT (Version 1) available at Research Square
https://doi.org/10.21203/rs.3.rs-3390900/v1

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