The production of orodispersible films (ODFs) with suspended insoluble drug substances is still a challenge, mainly due to the difficulty associated with achieving a proper homogeneity and mechanical properties of the films. Hypromellose (HPMC) and a mixture of polyvinyl alcohol (AP) and povidone (PVP) were compared in terms of their suitability for ODFs incorporating suspended micronized loratadine (LO) in a concentration range of 10%–40%. In a planetary mixer (Thinky), a uniform dispersion of LO in an aqueous viscous casting solution was obtained. The suspended LO particles caused dose-dependent changes in the viscosity of the casting mass and affected the mechanical quality of ODFs. Drug concentrations higher than 30% reduced the film flexibility and tear resistance, depending on the polymer type. LO films with a thickness of 100 µm disintegrated within 60-100 s, with no significant influence of the LO content in the range 10%–30%. HPMC films, regardless of the drug concentration, met the pharmacopoeial requirements regarding the uniformity of the drug content. AP/PVP films were too elastic, and the drug content uniformity was not achieved. The conclusion is that, using an HPMC matrix, it is possible to obtain a high load of a poorly water-soluble drug (30% of dry film mass corresponds to a dose of 5 mg per 1.5 cm²) in ODFs characterized by proper physical characteristics.

Orodispersiblefilms(ODFs) have served as an emerging platform for the delivery of drugs in a convenient way. The production of ODFs with incorporated pellets may still be a challenging process due to problems to obtain proper homogeneity and deteriorating mechanical properties of the films with incorporated relatively big particles in high concentration. The goal of this work was to evaluate the possibility to achieve fast disintegrating ODFs with homogenously incorporated spherical granules without loss of required mechanical properties. Hypromellose films with incorporated placebo pellets (size 200 µm or 100 µm) in a content range of 20-45 % w/w were prepared by a solvent casting method. Planetary mixer (Thinky) was successfully applied for preparation of a homogeneous mass for casting. The suspended spherical solid particles caused dose and size dependent changes in the mechanical properties and disintegration behaviour of ODFs films, but only 100 µm pellets in concentration higher than 40 % reduced significantly the tear resistance. The films with the pellets disintegrated faster and the larger particles reduced the disintegration time by 60 %. Good homogeneity of pellets distribution, expressed as a number of the particles per unit area, was confirmed for films obtained with a gap height 500 or 800 µm.

The skin acts as a dynamic barrier-combining physical, chemical, and immunological defences-while hosting a diverse microbiome essential for cutaneous homeostasis. Dysbiosis and impaired redox balance are linked to various inflammatory conditions; however, the mechanisms by which microbial signals regulate skin cell senescence remain unclear. This study evaluated the effects of Lactobacillus-derived extracellular vesicles (EVs) on human keratinocytes (HaCaTs) and dermal fibroblasts (HDFs) under both physiological and stress-induced premature senescence (SIPS) conditions. SEM analysis confirmed the presence of spherical membrane-bound structures consistent with EV morphology, providing a qualitative characterisation. Functional assays indicate that low concentrations of EVs (1.25-2.5% v/v) increase the metabolic activity of HaCaT cells; however, only the 1.25% v/v concentration significantly promotes early wound closure, whereas the 2.5% v/v concentration induces a decoupling between metabolism and motility. In HDFs, EVs significantly reduced basal intracellular reactive oxygen species (ROS) levels, demonstrating an inherent capacity to modulate redox homeostasis. Furthermore, immunofluorescence analysis revealed that EVs exert cell-specific and context-dependent modulatory effects on the DNA damage response (DDR) and senescence-associated secretory phenotype (SASP). While EVs significantly regulated p21, 53BP1, and MMP-3 expression across both cell types under both basal and SIPS conditions, a specific modulation of COX-2 was observed exclusively in fibroblasts following SIPS induction. These results indicate that Lactobacillus-derived EVs support epidermal regeneration and protect dermal cells from molecular senescence by modulating redox-sensitive pathways. Our findings highlight the potential of these vesicles as multifunctional postbiotic regulators-providing a mechanistic basis for future strategies aimed at maintaining skin homeostasis and mitigating cellular ageing.

The development of age-appropriate pediatric dosage forms remains an important challenge, particularly for acid-labile drugs requiring gastro-resistant protection. Pantoprazole, a proton pump inhibitor, must be protected from gastric acid until intestinal absorption; however, conventional enteric-coated tablets may be difficult to use in younger children, while manipulation of dosage forms or mixing with food can compromise dose accuracy and drug release performance. Multiparticulate systems, such as minitablets, pellets, or granules, offer flexible dosing but may still require a suitable vehicle to improve acceptability, handling, and ease of swallowing. In this study, enteric-coated pantoprazole minitablets were developed and evaluated after dispersion in selected hydrogel vehicles intended to serve as standardized alternatives to food-based carriers. Hydrogels based on hypromellose (HPMC), carbomer (CAR), and sodium alginate (SA) were characterized in terms of pH, rheological properties, firmness, acid penetration, and their effect on pantoprazole release. Dissolution performance was assessed using both conventional pharmacopoeial testing and dynamic non-pharmacopoeial conditions. Low-concentration gels prepared from high-viscosity HPMC grades showed the most favorable performance, combining suitable spoonable consistency with limited impact on drug release. Among them, 5% HPMC 65SH4000 was particularly promising, as it did not markedly delay pantoprazole release in either pharmacopoeial or dynamic dissolution testing. CAR gels provided advantageous rheological properties, including high viscosity at rest and shear-thinning behavior, and allowed efficient pantoprazole release after transition to buffer conditions; however, their interaction with enteric-coated minitablets should be further optimized with respect to gel amount, concentration, and neutralization strategy. SA gel showed strong structural persistence and delayed release under pharmacopoeial conditions, although this effect was less pronounced in the dynamic model. Overall, the findings indicate that appropriately selected hydrogels may improve the practical use of pediatric multiparticulate formulations, but their composition, pH, rheology, and interaction with enteric coatings must be carefully evaluated.