Despite extensive development and widespread use, existing methods for analysis of caffeine and paracetamol overlook their environmental impact. Furthermore, these methods were not developed using the Analytical Quality by Design approach, leading to a significant gap in understanding critical separation factors. Moreover, the absence of a hydrophilic interaction liquid chromatography (HILIC) method for the simultaneous analysis of caffeine and paracetamol, integrating Analytical Quality by Design and a comprehensive green approach, presents an exciting opportunity for innovation and advancement in the field. In this paper, we report an efficient and sustainable HILIC method for caffeine and paracetamol analysis, which is based on Analytical Quality by Design, green and white chemistry principles. Optimal chromatographic conditions were adjusted using an InertSil Diol column with the mobile phase of acetonitrile and ammonium acetate buffer. The method was validated according to the International Council for Harmonisation guidelines, and its applicability in the analysis of Panadol Extra® tablets was confirmed. Relative standard deviation values were 0.07–0.28% for accuracy and 0.45–0.54% for precision. The environmental footprint and effectiveness of the method were evaluated through assessments of triple-color analysis which showed the dominance of green, blue, and white with scores of 0.66, 85.0, and 83.3, respectively. These parameters confirm that the method is eco-friendly, reliable, accurate, and precise for future use in the analysis of dosage forms containing caffeine and paracetamol. This is the first time that the Analytical Quality by Design approach has been combined with green and white chemistry principles, creating a strong synergy for the development of environmentally friendly methods.

The development of advanced macromolecular systems with tailored structural and functional properties is a key objective in modern materials science, particularly for biomedical applications such as targeted drug delivery. In this study, hydrogel (HG), a polymer-based formulation, was investigated as a functional carrier for the enhanced intradermal and transdermal delivery of propranolol hydrochloride (PRO-HCl), a highly water-soluble model compound, and its potential was compared to other vehicles easily obtained by pharmacists: ointment (OM), liposomal cream (LCR), and microemulsion (ME). The formulations were characterized by their physicochemical and rheological characteristics, and evaluated in vitro and ex vivo using vertical diffusion cells equipped with synthetic membranes, intact porcine skin, and skin pretreated with solid microneedles (MNs). The HG formulation exhibited superior release performance (2396.85 ± 48.18 μg/cm²) and the highest intradermal drug deposition (19.87 ± 4.12 μg/cm²), while its combination with MNs significantly enhanced transdermal permeation (p = 0.0017). In contrast, the synergistic effect of MNs and ME led to a pronounced increase in drug accumulation within the skin (up to 60.3-fold). These findings highlight the crucial role of matrix composition and properties in modulating molecular transport through biological barriers. The study demonstrates that polymeric HGs represent versatile, functional materials with tunable structural and mechanical features, suitable for controlled release and potential systemic delivery applications.

Pomegranate peel, an abundant agro-industrial by-product, represents a sustainable source of bioactive polyphenols, particularly punicalagin, which has been associated with antioxidant and photoprotective potential. This study aimed to develop microemulsions (MEs) containing pomegranate peel extract for dermal delivery of punicalagin using biocompatible surfactant systems. Three MEs differing in surfactant–cosurfactant composition (ME-A, ME-P, and ME-E) were prepared. Each formulation solubilized 1% (w/w) of pomegranate peel extract and was evaluated regarding in vitro release behavior, skin permeation/retention, antioxidant activity, and in vitro sun protection factor (SPF). All investigated MEs provided sustained release of punicalagin (≈10–17% of the applied dose in 8 h). ME-A, based on an alkyl polyglucoside surfactant, showed a significantly higher cumulative release of punicalagin (60.4 µg/cm²) compared with ME-E and ME-P. In skin penetration/permeation studies, ME-A also exhibited the highest numerical total delivery of punicalagin (≈48.2 µg/cm² after 24 h), although differences among formulations were not statistically significant. All formulations demonstrated high antioxidant activity in the DPPH assay and measurable in vitro photoprotective potential, with SPF values ranging from approximately 11 to 14. Overall, pomegranate peel extract-loaded MEs showed potential as dermal delivery systems capable of improving solubilization and modulating skin delivery of punicalagin. The combination of agro-waste-derived bioactives with biocompatible surfactants highlights the potential of these systems as sustainable approaches for skincare formulations.