Stéphanie Briançon

Background/Objectives: The pharmaceutical industry demands stringent regulation of product characteristics and strives to ensure the reproducibility of granules manufactured via the wet granulation process. A systematic model employing the discrete element method (DEM) was developed herein to gain insights into and better control this process. Methods: The model comprehensively simulates particle behavior during granulation by considering the intrinsic properties of the powder material, the specific geometry of the granulation equipment, and various operational conditions, including impeller speed and chopper use. Notably, this approach can simulate dynamic interactions among particles and integrate complex phenomena, such as cohesion, which is crucial for predicting the formation and quality of granules. Results: To further support process optimization, an EDEMpy artificial intelligence (AI) tool was developed as a posttreatment routine to monitor and analyze agglomerate size distributions, proving essential for assessing the efficiency of the granulation process and the quality of resulting granules. The DEM model was evaluated by comparing its output with experimental data collected from a 0.5 L high-shear granulator. The model reproduced the granule growth kinetics observed experimentally, confirming the agreement between the experimental and numerical analyses. Conclusions: This underscores the model’s potential in predicting and controlling granule quality in wet granulation processes, enhancing the precision and efficiency of pharmaceutical manufacturing.

Conventional therapies for inflammatory bowel diseases are mainly based on systemic treatments which cause side effects and toxicity over long‐term administration. Nanoparticles appear as a valid alternative to allow a preferential accumulation in inflamed tissues following oral administration while reducing systemic drug exposure. To increase their residence time in the inflamed intestine, the nanoparticles are here associated with a hydrogel matrix. A bioadhesive peptide‐based hydrogel is mixed with nanoemulsions, creating a hybrid lipid‐polymer nanocomposite. Mucopenetrating nanoemulsions of 100 nm are embedded in a scaffold constituted of the self‐assembling peptide hydrogel product PuraStat. The nanocomposite is fully characterized to study the impact of lipid particles in the hydrogel structure. Rheological measurements and circular dichroism analyses are performed to investigate the system's microstructure and physical properties. Biodistribution studies demonstrate that the nanocomposite acts as a depot in the stomach and facilitates the slow release of the nanoemulsions in the intestine. Efficacy studies upon oral administration of the drug‐loaded system show the improvement of the disease score in a mouse model of intestinal inflammation.

Muscular Dystrophies (MDs) are a group of rare inherited genetic muscular pathologies encompassing a variety of clinical phenotypes, gene mutations and mechanisms of disease. MDs undergo progressive skeletal muscle degeneration causing severe health problems that lead to poor life quality, disability and premature death. There are no available therapies to counteract the causes of these diseases and conventional treatments are administered only to mitigate symptoms. Recent understanding on the pathogenetic mechanisms allowed the development of novel therapeutic strategies based on gene therapy, genome editing CRISPR/Cas9 and drug repurposing approaches. Despite the therapeutic potential of these treatments, once the actives are administered, their instability, susceptibility to degradation and toxicity limit their applications. In this frame, the design of delivery strategies based on nanomedicines holds great promise for MD treatments. This review focuses on nanomedicine approaches able to encapsulate therapeutic agents such as small chemical molecules and oligonucleotides to target the most common MDs such as Duchenne Muscular Dystrophy and the Myotonic Dystrophies. The challenge related to in vitro and in vivo testing of nanosystems in appropriate animal models is also addressed. Finally, the most promising nanomedicine-based strategies are highlighted and a critical view in future developments of nanomedicine for neuromuscular diseases is provided.

Objective Thermal spring waters (TSW) are commonly used as active ingredients in cosmetics. Their biological activities directly depend on the ionic composition of the spring. However, in order to exhibit beneficial properties, the minerals need to reach viable skin layers. The present study addresses the incorporation of marketed TSW in model cosmetic formulations and the impact of the formulation on skin absorption of magnesium and calcium ions that are known to improve skin barrier function. Methods Marketed TSW was introduced into five formulations. Liposomes were prepared using saturated or unsaturated phospholipids mixed with cholesterol by the thin layer evaporation technique. Emulsions water‐in‐oil (W/O), oil‐in‐water (O/W) or double: water‐in‐oil‐in‐water (W/O/W) were prepared by high shear mixing. Skin absorption of Mg²⁺ and Ca²⁺ from those formulations was studied in vitro using static Franz diffusion cells under infinite dose condition and under occlusion of the apparatus. Results Mg²⁺ and Ca²⁺ penetrate skin samples from TSW. Encapsulating TSW into double emulsion (TSW/O/W) increased skin absorption of both cations of interest and kept the Ca²⁺/Mg²⁺ ratio equal to that of TSW in each skin layer. The dermal absorption of Mg²⁺ from the double emulsion departs from both single emulsions. Application of liposome suspension improved the skin absorption of Ca²⁺ while keeping constant that of Mg²⁺, leading to unbalanced Ca²⁺/Mg²⁺ ratio inside skin. Conclusion The beneficial effects of TSW are not only due to their action on the skin surface. Their active components, especially Ca²⁺ and Mg²⁺ cations reach viable skin layers in a formulation‐dependent manner. The distribution of ions inside skin depends on the type of formulation.