Paracetamol 1g/100ml / Ibuprofen 300mg/100ml solution for infusion vials

AimsFever is one of the most frequent reasons for paediatric consultations. While traditionally managed by reducing body temperature, recent guidelines emphasize alleviating discomfort as the primary therapeutic goal. Although different interventions have been described to manage fever-associated discomfort in children, their effectiveness and safety has never been systematically analysed. The aim of this study was to review the evidence on the effectiveness and safety of pharmacological and nonpharmacological interventions for managing discomfort in febrile children.MethodsA systematic review was conducted following PRISMA guidelines (PROSPERO: CRD420250655721). PubMed, Embase and Cochrane Library were searched up to 31 January 2025, for studies involving children aged 29 days to 18 years that assessed interventions for fever-associated discomfort. Randomized controlled trials and observational studies were included. Risk of bias was assessed using Cochrane and STROBE tools. Results were synthesized narratively and grouped according to the type of intervention.ResultsEight studies (5 randomized controlled trials, 3 observational) involving 1877 children were included. Study designs, including dosage of antipyretics and quality varied across studies. Studies comparing ibuprofen and paracetamol provided conflicting results, while combination therapy (paracetamol + ibuprofen) appeared more effective than using a single drug in -one trial. Tepid sponging, despite reducing temperature, was associated with increased discomfort. No serious adverse events were reported.ConclusionPharmacological treatments appear effective and safe, whereas physical methods offer limited benefit. The available evidence is limited by the small number of studies, methodological heterogeneity, and concerns about risk of bias and outcome measurement inconsistency. New high-quality studies are needed to guide clinical practice for the management of fever-associated discomfort in children.

Abstract licence: CC BY

Background: Sustained-release (SR) formulations of non-steroidal anti-inflammatory drugs (NSAIDs) aim to prolong therapeutic activity, reduce dosing frequency, and improve patient adherence. However, currently marketed SR NSAIDs exhibit persistent limitations, including incomplete control over release kinetics, high interpatient variability in bioavailability, limited reduction in gastrointestinal adverse effects, and insufficient dose flexibility for individualized therapy. In many cases, conventional excipients and release mechanisms remain predominant, leaving drug-specific physicochemical and pharmacokinetic constraints only partially addressed. These gaps highlight the need for a comprehensive synthesis of recent technological advances to guide the development of more effective, patient-centered delivery systems. Methods: A narrative literature review was conducted using Web of Science and PubMed databases to identify original research articles and comprehensive technological studies on oral SR formulations of NSAIDs and paracetamol published between January 2020 and March 2025. Inclusion criteria focused on preclinical and technological research addressing formulation design, excipient innovations, and manufacturing approaches. Results: Sixty-four studies met the inclusion criteria, encompassing polymeric matrices (31%), lipid-based carriers (18%), microspheres/hydrogel beads/interpenetrating polymer networks (30%), nanostructured systems (11%), and hybrid platforms (10%). The most common strategies involved pH-dependent release, mucoadhesive systems, and floating drug delivery, aiming to optimize release kinetics, minimize mucosal irritation, and sustain therapeutic plasma levels. Advances in manufacturing-such as hot-melt extrusion, 3D printing, electrospinning, and spray drying-enabled enhanced control of drug release profiles, improved stability, and in some cases up to 30-50% prolongation of release time or reduction in Cmax fluctuations compared with conventional formulations. Conclusions: Recent formulation strategies show substantial potential to overcome long-standing limitations of SR NSAID delivery, with expected benefits for patient compliance and quality of life through reduced dosing frequency, better tolerability, and more predictable therapeutic effects. Nevertheless, integration of in vitro performance with pharmacokinetic and clinical safety outcomes remains limited, and the translation to clinical practice is still in its early stages. This review provides a comprehensive overview of current technological trends, identifies persisting gaps, and proposes future research directions to advance SR NSAID systems toward safer, more effective, and patient-focused therapy.

Abstract licence: CC BY