alfuzosin hydrochloride + solifenacin (Solitral)

Development of propranolol hydrochloride extended-release lipid matrix tablets for pediatric use.

Broocks Stefanie S, Gebhardt Melanie M, Klein Sandra S

Although solid oral dosage forms are widely used in adult drug therapy, age-appropriate formulations for pediatric patients remain limited. The development of suitable dosage forms is challenged by specific requirements regarding excipient safety, tablet size, and dose flexibility, as well as the need to improve therapy adherence in the context of frequent dosing. This study aimed to develop a pediatric-appropriate extended-release matrix tablet based on lipid matrix formers, with particular attention to the use of safe excipients and the selection of excipients based on sustainability considerations. Lipid-based excipients, selected due to their natural origin and similarity to dietary fats, were investigated and compared with conventional matrix formers. A formulation screening approach was applied to identify promising candidates based on drug release after one hour, followed by further evaluation of manufacturability, tablet hardness, and extended-release performance. In addition, the influence of a physiological pH-gradient, bile salts, and long-term storage on drug release was assessed. The selected formulations showed good manufacturability, uniformity, and sustained drug release. Overall, several lipid-based matrix formulations suitable for pediatric use were identified, providing a promising basis for the development of solid oral extended-release dosage forms for children.

Multifunctional antimicrobial effects of Lactobacillus johnsonii against A/E pathogens Enteropathogenic E. coli and Citrobacter rodentium.

Vasamsetti Sai Madhuri SM, Khaderbad Yasaswi Y, Sarmah Novelina N, Atham Hari Naga Papa Rao HNPR et al.

Enteropathogenic Escherichia coli (EPEC) remains a leading cause of childhood diarrhea in low-resource settings, and escalating antimicrobial resistance necessitates non-antibiotic therapeutic approaches. This study investigates Lactobacillus johnsonii as a probiotic candidate capable of limiting A/E-pathogen colonization and attenuating infection-associated intestinal inflammation. The probiotic properties of L. johnsonii were evaluated through assays of gastrointestinal tolerance, epithelial adhesion, antimicrobial activity, biofilm inhibition, and pathogen exclusion. Secreted antimicrobial activity was investigated by fractionation and untargeted metabolomic profiling. Therapeutic efficacy was further assessed in an antibiotic-perturbed Citrobacter rodentium mouse infection. L. johnsonii exhibited robust gastrointestinal resilience (acid pH 1.5-2.5; 0.3% bile) and strong adhesion to human intestinal epithelial cells. In vitro, live L. johnsonii markedly inhibited EPEC growth, disrupted pre-formed biofilms, and displaced adherent pathogens from epithelial surfaces. In an antibiotic-perturbed Citrobacter rodentium infection model, oral L. johnsonii administration reduced pathogen loads in feces and colonic tissues by 3-4 log units, restored colon length, and alleviated epithelial ulceration and inflammatory infiltration. Mechanistic analyses revealed dual antimicrobial actions: nutrient competition and secretion of low-molecular-weight (<75 kDa) bactericidal factors active at ~30 µg mL-1. Untargeted metabolomic profiling of the active fraction generated putative annotations of chemically diverse small molecules, including fatty-acid and hydroxy-acid class compounds, as well as candidate metabolites such as quinine hydrochloride, aloperine, and γ-glutamylglutamine, thereby providing a foundation for future targeted validation of individual antimicrobial components. Notably, probiotic treatment reduced mucosal neutrophil infiltration and preserved epithelial architecture, suggesting attenuation of infection-associated inflammation. Collectively, these findings support L. johnsonii as a multifunctional probiotic that integrates biofilm disruption, metabolic competition, and immune-protective activity. The study highlights its translational potential as a probiotic-based intervention to manage attaching-and-effacing enteric infections and mitigate antibiotic reliance in vulnerable populations.

Artificial Intelligence and Large Language Models as Decision-Support Tools in Hospital Compounding Pharmacy: A Proof-of-Concept Study.

Castellana Eleonora E, Chiappetta Maria Rachele MR

To evaluate the efficiency and reliability of a large language model (LLM) as a decision-support tool in hospital compounding pharmacy for pediatric extemporaneous preparations requiring assessment of drug crushability, regulatory compliance, and formulation feasibility. A proof-of-concept study compared a structured LLM-assisted workflow with the traditional manual information retrieval process in a hospital pharmacy setting. The LLM (Claude Sonnet 4.6) was configured with a standardized prompt to extract and consolidate data from multiple authoritative sources: the Friuli Venezia Giulia "Do Not Crush" list, the Italian Medicines Agency (AIFA) database for Summary of Product Characteristics (SmPC), AIFA Law 648/96 off-label use lists, and the Stabilis database for oral liquid formulation stability. Two representative drugs, propranolol hydrochloride and imatinib mesylate, were analyzed. For each drug, the model generated a structured output including crushability, regulatory information, off-label status, and extemporaneous formulation data. The same queries were manually performed by an experienced hospital pharmacist. Primary outcome was information retrieval time; secondary outcomes included completeness and accuracy. The LLM-assisted workflow reduced retrieval time to less than 2 minutes per drug (mean 1 minute 45 seconds), compared with a mean of 20 minutes (range 15-25 minutes) for the manual process, plus an additional 5 to 10 minutes for transcription. Output completeness was 100%, with all predefined fields correctly populated. The model accurately classified drug crushability and correctly identified Law 648/96 regulatory status. For propranolol, the system identified crushability, pediatric off-label authorization, and SyrSpend-based formulations with stability data of up to 146 days at room temperature. For imatinib, the model highlighted cytotoxic handling precautions, identified the absence of SyrSpend formulations, and retrieved alternative formulation stability data (30 days refrigerated). A properly configured LLM can function as an effective decision-support tool in hospital compounding pharmacy, improving efficiency while maintaining high standards of completeness, accuracy, and regulatory compliance. These preliminary results support further investigation into the integration of the LLM system into routine pediatric galenical preparation practice.

Editorial Comment on "Quantitative assessment of additive effects ofmirabegrin and solifenacin in overactive bladder: re-analysis of SYNERGY study".

Kuo Hann-Chorng HC