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

Abstract

The study aimed to create a low loading, high retention, easier to apply O/W mometasone furoate (MF) cream using a chemical enhancer (CE) approach to provide more options for patients with atopic dermatitis (AD) and to investigate molecular mechanisms of its increased release and retention. A Box-Behnken design determined the optimal formulation based on stability and in vitro skin retention. Evaluations included appearance, rheological properties, irritation, in vivo tissue distribution and pharmacodynamics.

Molecular mechanisms of enhanced release were studied using high-speed centrifugation, molecular dynamics and rheology. The interaction between the CE, MF and skin was studied by tape stripping, CLSM, ATR-FTIR and SAXS. The formulation was optimized to contain 0.05% MF and used 10% polyglyceryl-3 oleate (POCC) as the CE. There was no significant difference from Elocon® cream in in vivo retention and pharmacodynamics but increased in vivo retention by 3.14-fold and in vitro release by 1.77-fold compared to the basic formulation.

POCC reduced oil phase cohesive energy density, enhancing drug mobility and release. It disrupted skin lipid phases, aiding drug entry and formed hydrogen bonds, prolonging retention. This study highlights POCC as a CE in the cream, offering insights for semi-solid formulation development.

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Materials

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 TM lipophile WL 1349 (LWL1349), Gelot TM 64, Labrafil® M194 4CS (LM1944), Plurol® Oleique CC 497 (Polyglyceryl-3 oleate, POCC), Transcutol® P (TP), Lauroglycol®FCC (FCC) were purchased from GATTEFOSSé

Wenxuan Jia, Yu Pang, Chenyu Zhao, Yu Cai, Yang Zhang, Chao Liu, Liang Fang, 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, International Journal of Pharmaceutics, Volume 659, 2024, 124284, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2024.124284.