Sonia Iurian

Age-appropriate dosage forms with flexible dosing remain a challenge in pediatric pharmacotherapy. This study investigated infant formula-based oral lyophilizates containing loratadine at doses of 5 mg and 10 mg, prepared using different fill volumes (0.2-0.5-1.0 mL). The formulations were evaluated for disintegration, mechanical properties, in vitro dissolution, particle size, thermal behavior and morphology. A preliminary pharmacokinetic study in Wistar rats compared a reconstituted lyophilizate with a conventional loratadine suspension. All formulations disintegrated within 6.21 s, and more than 97% of loratadine dissolved within 15 min. Differential scanning calorimetry revealed similar glass transition temperatures in the frozen milk-based suspensions (−21.71 °C to −22.31 °C), supporting the selection of primary drying conditions. Thermal and morphological analyses indicated changes in loratadine behavior following incorporation into the freeze-dried matrix. In vivo, systemic exposure was comparable between the lyophilizate dispersion and the reference suspension, with AUC_0–∞ values of 17.39 ± 10.14 and 18.21 ± 6.69 µg·h/mL, respectively. These findings support the potential of infant formula as a matrix for flexible-dose oral lyophilizates with loratadine.

Additive manufacturing, also known as 3D printing (3DP), is intended to enable personalised medicine by producing drug products on demand at the Point of Care (PoC), with dose, drug-release profile, and geometry tailored to the individual patient. Despite its promise, widespread adoption is limited by the absence of ready-to-use quality control (QC) methods for printlets at the PoC. Process Analytical Technology (PAT) tools, particularly vibrational spectroscopic methods like Near-Infrared and Raman spectroscopy, can offer real-time monitoring to ensure the safety and consistency of printed dosage forms. Integrating these tools within a Quality-by-Design (QbD) framework can enhance process understanding, control variability, and minimise risk. Regulatory implementation and technological innovation remain essential for the broader clinical implementation of 3DP in pharmaceutical manufacturing. This review presents an overview of currently existing studies on PAT tools explored for non-destructive quality control across 3DP techniques, examines the correlation between Critical Process Parameters (CPPs), Critical Material Attributes (CMAs), and the Critical Quality Attributes (CQAs) of 3D-printed dosage forms within a QbD context, and outlines the current regulatory landscape alongside key limitations and future directions for the broader integration of 3DP into pharmaceutical development and manufacturing. Current evidence shows that PAT application remains uneven across printing technologies and is predominantly directed at final product quality control, rather than the real-time process monitoring required for a fully closed-loop QbD framework. Existing spectroscopic models are largely restricted to single formulations, printers, and APIs, and the absence of standardised validation reporting and transferability assessments represents a key barrier to routine implementation.

The manufacturing of drug-loaded filaments aimed for fused deposition modeling (FDM) three-dimensional printing (3DP) is still an important challenge because the filament mechanical profile and printing performance depend on both formulation and process-related factors. This study investigated the impact of extrusion technology on the mechanical properties and printability of paracetamol-loaded polyvinyl alcohol filaments with variable compositions. Filaments with compositions according to a full-factorial design were processed by single-screw extrusion (SSE) and twin-screw extrusion (TSE). Mechanical properties were assessed using the 3-point bending test and stiffness test. The thermal behavior of the components was evaluated through differential scanning calorimetry (DSC), while printability was evaluated through feeding and printing tests. Both formulation factors affected mechanical performance. High paracetamol content generally reduces stiffness and flexural resistance while increasing deformation capacity, suggesting a secondary plasticizing effect in the studied concentration range. Mannitol exhibited limited plasticizing efficiency, with flexibility decreasing at high ratios. DSC indicated partial crystallinity after extrusion, with TSE showing lower residual melting enthalpies than SSE. TSE filaments provided higher model reproducibility, broader mechanical ranges, and higher printability scores. This study shows that formulation effects depended strongly on extrusion technology and highlights TSE as a more robust platform for producing printable pharmaceutical filaments.

Objectives: The current study presents a sequential strategy for the development of directly compressible powder formulations relying on Design of Experiments (DoE) and Compactibility-Ejection stress plots. Methods: Compression analysis was used to evaluate the impact of changing the sort of microcrystalline cellulose (MCC), dicalcium phosphate (DCP), the diluent ratio, lubricant type, and the inclusion of an API from different suppliers. Results: The effect of DCP particle size on the ejection stress was efficiently mitigated in the placebo formulations by lubrication. However, the initial differentiation between sorts was highlighted at a smaller scale when the active pharmaceutical ingredient (API) was included in the formulation. For MCC, the tensile strength was positively correlated with the level of plasticity and tabletability capacity of different sorts. The particle size was a critical attribute for the API, influencing the detachment and ejection stress values. Fine particles (d50 = 30 µm) presented increasing stress values once the compression force rose, while for coarser particles (d50 = 50 µm) these effects were limited. Conclusions: Material-related variability must be understood to design products and processes with adequate performance. The proposed strategy enables early identification of critical material attributes, supporting rational formulation and supplier selection to ensure consistent quality during manufacturing.

Molecularly imprinted polymers (MIPs) are tailor-made functional polymers increasingly acknowledged for their strong performance across scientific fields. However, conventional MIP synthesis often relies on complex chemical processes that hinder sustainable scale-up and industrial adoption. To address this challenge, modern production strategies should integrate advances in polymer science and industrial processing technologies to achieve greener and more scalable manufacturing. Solventless approaches represent a promising route, offering not only environmental benefits but also enhancing the affinity and selectivity of MIP binding sites. They can also mitigate common issues such as solubility limitations of key components, as well as the disruption of template–monomer interactions by solvents. In this context, mechanochemistry emerges as a particularly attractive strategy, enabling shorter polymerization times, higher yields, improved control over polymeric architecture, and eliminating solvent-related constraints. This pioneering study explores the influence of key mechanochemical variables on MIP performance, demonstrating that solid-state MIP synthesis operates under distinct principles from solution-based methods and positioning mechanochemical imprinting as a highly efficient, scalable, and sustainable alternative, while also revealing that minute amounts of aprotic solvent—with the appropriate balance of polarity, basicity, polarizability, and hydrogen bond accepting ability—remain essential to achieve mechanochemically imprinted MIPs with impressive molecular recognition performance.

This study offers a detailed assessment of the polyphenolic composition and antioxidant, anti-inflammatory, and cardioprotective properties of lyophilized extracts derived from the aerial parts of Agastache mexicana and Agastache scrophulariifolia. The polyphenolic content was determined through the quantification of total polyphenols, flavonoids, and caffeic acid derivatives, complemented by LC-MS profiling. The antioxidant activity was evaluated in vitro using DPPH and FRAP assays, while the in vivo antioxidant and anti-inflammatory effects were investigated in a rat model of turpentine-oil-induced acute inflammation. Cardioprotective potential was assessed in a separate rat model of isoprenaline-induced myocardial infarction. Phytochemical analysis revealed a complex polyphenolic profile for both species, with tilianin and rosmarinic acid identified as predominant compounds. In the DPPH assay, both extracts exhibited marked radical scavenging activity (IC₅₀: 65.91 ± 1.21 μg/mL for A. mexicana; 68.64 ± 2.48 μg/mL for A. scrophulariifolia). In the in vivo assays, the administration of the extracts significantly decreased pro-oxidant biomarkers (TOS, OSI, MDA, NO) and enhanced antioxidant markers (TAC, SH groups). Furthermore, the extracts led to a significant reduction in serum levels of GOT, GPT, and CK-MB in rats subjected to myocardial injury, supporting their cardioprotective efficacy. Overall, the results suggest that A. mexicana and A. scrophulariifolia represent promising natural sources of polyphenolic compounds with potential therapeutic value in oxidative-stress-related inflammatory and cardiovascular disorders.

This study aimed to design self-adhesive cutaneous films with an antiallergic effect using a Design of Experiments approach. The active pharmaceutical ingredient (API) was diphenhydramine hydrochloride (DPH). A full factorial experimental design with three factors and two levels was created. The factors were the polyvinyl alcohol (PVA) ratio, the polyacrylic acid (PAA) ratio, and the type of plasticizer. The responses evaluated were hardness, deformation at hardness, adhesive force, and in vitro DPH release profile. Eleven formulations were generated, prepared in two steps via solvent casting, and characterized in terms of mechanical and adhesive properties, as well as the in vitro DPH release profile. The PVA ratio had the most significant impact on the responses, followed by PEG 400 and PEG 4000. Four film formulations were investigated using Raman spectroscopy, which revealed that the API was distributed in both the base and adhesive layers. Consequently, an optimal formulation was prepared and characterized. Good mechanical properties (a hardness of 463.7 g and a deformation at hardness of 16.56 mm) and an increased adhesive force (76 g) were observed, while the DPH was released up to 68% over 12 h. In conclusion, a novel self-adhesive film was developed, which may enhance patients’ adherence to local antiallergic treatment.

This study aimed to optimize the extraction of phytocompounds intended for wound care applications from three plant species, Sambucus nigra L. flowers and Epilobium hirsutum L. and Lythrum salicaria L. aerial parts, by using a Quality by Design approach. The effects of different extraction methods (ultra-turrax and ultrasonic-assisted extraction), ethanol concentrations (30%, 50%, 70%), and extraction times (3, 5, 10 min) were studied, and during the optimization step, the polyphenol and flavonoid contents were maximized. The phytochemical profiles of the optimized HEs (herbal extracts) were assessed using LC-MS/MS methods. The antioxidant capacity of the optimized HEs was determined using DPPH (2,2-diphenyl-1-picrylhydrazyl radical scavenging capacity) TEAC (Trolox equivalent antioxidant capacity), and FRAP (ferric reducing antioxidant power) assays, while the antibacterial activity was evaluated against Escherichia coli, Pseudomonas aeruginosa, and MSSA—methicillin-sensitive Staphylococcus aureus and MRSA—methicillin-resistant Staphylococcus aureus). Cell viability and antioxidant and wound healing potential were assessed on keratinocytes and fibroblasts. The anti-inflammatory effect was assessed on fibroblasts by measuring levels of interleukins IL-6 and IL-8 and the production of nitric oxide from RAW 264.7 cells. The major compounds of the optimized HEs were rutin and chlorogenic acid. The Lythrum salicaria optimized HE showed the strongest antibacterial activity, while the Sambucus nigra optimized HE demonstrated high cell viability. Lythrum salicaria and Epilobium hirsutum optimized HEs showed increased antioxidant capacities. All extracts displayed anti-inflammatory effects, and the Epilobium hirsutum optimized HE exhibited the best in vitro wound-healing effect.