European Journal of Pharmaceutical Sciences最新文献

{"title":"Functional enzyme delivery via surface-modified mesoporous silica nanoparticles in 3D printed nanocomposite hydrogels","authors":"Alaa Mahran ,&nbsp;Fadak Howaili ,&nbsp;Rajendra Bhadane ,&nbsp;Rathna Mathiyalagan ,&nbsp;Tapani Viitala ,&nbsp;Xiaoju Wang ,&nbsp;Jessica M. Rosenholm","doi":"10.1016/j.ejps.2025.107132","DOIUrl":"10.1016/j.ejps.2025.107132","url":null,"abstract":"<div><div>Three-dimensional (3D) printed hydrogel-based scaffolds have emerged as promising for the delivery of biologicals. Recently, we developed a printable plant-based nanocomposite hydrogel, composed of anionic cellulose nanofibers (T-CNF) and methacrylated galactoglucomannan (GGMMA), reinforced with mesoporous silica nanoparticles (MSNs) of different surface charges. However, ensuring the biological activity of the delivered biomolecules requires further investigation to validate the functionality of the developed biomaterial. To investigate this, in this study, horseradish peroxidase (HRP) and lysozyme were selected as distinct model proteins, assessing their immobilization stability and biological activity after MSN immobilization and 3D printing. The interactions between the enzymes and differently surface-modified MSNs were explored using multi-parametric surface plasmon resonance (MP-SPR) and molecular dynamics (MD) simulations. We observed that MSN surface charge is key to the extent of enzyme adsorption and activity control. Positively charged MSNs showed the highest HRP immobilization but caused significant activity loss in both enzymes. In contrast, near-neutral and negatively charged MSNs provided improved stability and activity retention for HRP and lysozyme, respectively. Except for lysozyme/hydrogel, HRP/hydrogel and enzyme-loaded nanocomposite hydrogels (HRP-loaded near-neutral and lysozyme-loaded negatively charged MSNs) were successfully 3D printed using different UV post-curing times. While enzyme-laden nanocomposite scaffolds showed promising immobilization stability, the presence of the photoinitiator caused significant inactivation for both enzymes. Irrespective of the crosslinking approach, this matrix demonstrates significant potential as a delivery carrier for various biomolecules, with promising applications in tissue engineering and wound healing.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"211 ","pages":"Article 107132"},"PeriodicalIF":4.3,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combining high-throughput ASD screening with the rDCS to streamline development of poorly soluble drugs","authors":"Malte Bøgh Senniksen ,&nbsp;Nicole Wyttenbach ,&nbsp;Susanne Page ,&nbsp;Jennifer Dressman","doi":"10.1016/j.ejps.2025.107130","DOIUrl":"10.1016/j.ejps.2025.107130","url":null,"abstract":"<div><div>Poor aqueous solubility and slow dissolution rate of active pharmaceutical ingredients (APIs) are often encountered challenges during oral drug development, leading to variable and insufficient bioavailability. To overcome these challenges, a so-called “enabling” formulation strategy is often pursued. Among these, amorphous solid dispersions (ASDs) are established as an effective means of improving drug absorption. However, evaluating the outcome of in vitro ASD screening approaches and relating this to the expected bioavailability increase can be difficult if not done systematically. Here we show, for the first time, how the combination of a high-throughput ASD screening method with the refined Developability Classification System (rDCS) can streamline the formulation of poorly soluble APIs as ASDs. Using the Screening of Polymers for Amorphous Drug Stabilization (SPADS) approach to rapidly prepare ASD films, the improvement in dissolution performance of three APIs (befetupitant, celecoxib and itraconazole) was investigated with eight polymeric carriers. The results showed that the concentration of dissolved API was highly dependent on both the carrier and the drug load. For the APIs studied, Eudragit E, HPMC 100LV and Soluplus showed especially advantageous effects as carriers. Translating these results into the rDCS framework allowed for the visualization of the left-shift (more favorable for absorption) in classification. Several ASD films were classified as rDCS class I, showing a major improvement from the initial IIb classification of the pure API. This novel approach could be expanded to include a diverse set of screening methods for enabling formulation strategies, where the rDCS can allow for a direct comparison and support formulation selection.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"211 ","pages":"Article 107130"},"PeriodicalIF":4.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Global Bioequivalence Harmonisation Initiative (GBHI): Report of the sixth international EUFEPS/PQRI conference","authors":"B. Schug ,&nbsp;G. Beuerle ,&nbsp;E. Bilensoy ,&nbsp;J. Cook ,&nbsp;E. Fernandes ,&nbsp;S. Haertter ,&nbsp;R. Kuribayashi ,&nbsp;M. Mehta ,&nbsp;P. Paixao ,&nbsp;A. Seidlitz ,&nbsp;N. Tampal ,&nbsp;Y.-C. Tsang ,&nbsp;J. Walstab ,&nbsp;R. Wedemeyer ,&nbsp;J. Welink ,&nbsp;W. Jiang","doi":"10.1016/j.ejps.2025.107129","DOIUrl":"10.1016/j.ejps.2025.107129","url":null,"abstract":"&lt;div&gt;&lt;div&gt;At the 6&lt;sup&gt;th&lt;/sup&gt; International Conference of the Global Bioequivalence Harmonisation Initiative (GBHI), co-organised by the European Federation of Pharmaceutical Sciences (EUFEPS) and the Product Quality Research Institute (PQRI), critical bioequivalence (BE) topics were discussed by pharmaceutical scientists from academia, industry and regulatory agencies, revealing the following main conclusions:&lt;/div&gt;&lt;div&gt;(1) Physiologically based pharmacokinetic/biopharmaceutic modelling (PBPK/PBBM) for solid oral drugs: PBPK/PBBM gains increasing recognition for generic drug development, e.g. waivers of fed studies and drug interaction studies with proton pump inhibitors. However, especially for complex formulations containing low-solubility compounds, more data are needed for modelling-based conclusion regarding BE in fed state.&lt;/div&gt;&lt;div&gt;(2) Narrow therapeutic index drugs: A progress towards harmonisation of BE criteria from US-FDA and EMA speakers was made as there is consensus in the usefulness of applying a mixed scale for BE acceptance range depending on variability, via either fully or partially replicated design. Differences still remain regarding variability comparison and the selection of regulatory constant (0.760 vs. 1.05361). All parties confirmed the importance of controlling type-I error.&lt;/div&gt;&lt;div&gt;(3) Single- vs. multiple-dose studies for BE demonstration of modified-release (MR) products: To circumvent multiple-dose studies, model-informed approaches were discussed based on real-life data, e.g. to simulate steady-state profiles from single-dose data. To reduce the burden in patient trials for long-acting injectables promising modelling approaches were presented, extrapolating from incomplete steady-state scenarios.&lt;/div&gt;&lt;div&gt;(4) BE demonstration for additional dose strengths of solid oral MR products: For multiple-unit dosage forms where strengths differ in number of units only, testing BE of the highest dose was considered sufficient. In addition, there was some consensus that, whenever extrapolation from one strength to the others is not easily established, the “bracket-approach” of the EMA focusing on the intake conditions in the label claim (fasted or fed), can help mitigating risks without adding significant cost and effort.&lt;/div&gt;&lt;div&gt;(5) Partial AUC for BE demonstration: Clinical relevance is key to decide on the relevant PK metrics for BE assessment whenever possible. There was consensus that the BE criteria and evaluation strategy may be best specified in product-specific guidances – preferably with international harmonisation.&lt;/div&gt;&lt;div&gt;(6) BE of orally inhaled drug products (OIDPs): The “weight-of-evidence” approach of US-FDA and the stepwise approach of EMA largely differ. The auditorium was in favour of combining data on &lt;em&gt;in-vitro&lt;/em&gt; characteristics and PK exposure. For prediction of comparable efficacy of two OIDPs, there is good trust in PK exposure data whenever they present concentrations being absorbed vi","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"212 ","pages":"Article 107129"},"PeriodicalIF":4.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The 8th International Symposium on Phospholipids in Pharmaceutical Research – An update on current research in phospholipids presented at the biennial symposium of the Phospholipid Research Center Heidelberg","authors":"Simon Drescher ,&nbsp;Alfred Blume","doi":"10.1016/j.ejps.2025.107126","DOIUrl":"10.1016/j.ejps.2025.107126","url":null,"abstract":"<div><div>This <em>Conference Report</em> recaps recent advances in the research on phospholipids and their applications for advanced drug delivery and analytical purposes that have been presented at the <em>“8th International Symposium on Phospholipids in Pharmaceutical Research”</em> of the Phospholipid Research Center (PRC), held from September 09–11, 2024, at the University of Heidelberg, Germany. The PRC is a non-profit organization focused on expanding and sharing scientific and technological knowledge of phospholipids in pharmaceutical and related applications. This is accomplished by<em>, e.g.</em>, funding doctoral and postdoctoral research projects at universities worldwide. The PRC organizes this symposium every two years, at which international experts from science and industry present innovative and new applications of phospholipids. This year’s symposium highlighted advancements in lipid-based gene and RNA delivery, anisotropic lipid nanoparticles, PEGylation challenges, tetraether lipids for drug delivery, ethical considerations in publishing, multifunctional lipopeptides, and phospholipid applications in therapeutics. Discussions also showcased award-winning research on optimizing liposome drug compatibility, reflecting the expanding role of phospholipids in pharmaceutical science.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"210 ","pages":"Article 107126"},"PeriodicalIF":4.3,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced electrochemical immunosensor utilizing pATA/AuNPs for sensitive detection of the leukemia-associated biomarker CD123 in bone marrow supernatant","authors":"Xin Li ,&nbsp;Qing Wang ,&nbsp;Chun-Rong Qin ,&nbsp;Ai-Lin Liu ,&nbsp;Yong Chen","doi":"10.1016/j.ejps.2025.107124","DOIUrl":"10.1016/j.ejps.2025.107124","url":null,"abstract":"<div><h3>Background</h3><div>Cluster of differentiation 123 (CD123) prominently overexpress in various hematological malignancies and plays a crucial role in diagnosis and prognosis of leukemia. Clinical studies have demonstrated that cell-free CD123 levels also significantly influence leukemia immunotherapy outcomes. The development of novel electrochemical immunosensors addresses the need for point-of-care detection tools, thereby facilitating advancements in clinical monitoring technologies.</div></div><div><h3>Methods</h3><div>This study presented a practical electrochemical immunosensor constructed using sandwich strategy for CD123 detection based on the modification of gold nanoparticles and poly (2-aminoterephthalic acid). Common proteins and tumor-related biomarkers found in human were selected as interference factors to evaluate the detection specificity of the electrochemical immunosensor. Further, the electrochemical immunosensor was utilized to directly detect CD123 in bone marrow supernatant from leukemia patients.</div></div><div><h3>Results</h3><div>The constructed electrochemical immunosensor exhibited good linearity for CD123 detection over a range of 0.02 to 2.5 µg/mL, with a detection limit of 12.8 ng/mL, alongside satisfactory specificity and repeatability. Furthermore, the immunosensor was successfully employed to detect CD123 levels in the bone marrow supernatant of leukemia patients, demonstrating results that were highly consistent with those obtained via ELISA.</div></div><div><h3>Conclusions</h3><div>The developed approach is anticipated to provide robust technical support for the long-term monitoring of leukemia patients during their diagnosis and treatment.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"211 ","pages":"Article 107124"},"PeriodicalIF":4.3,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Can the pH-stat lipolysis model be used to assess the performance of supersaturated lipid-based type I formulations?","authors":"Felix Paulus ,&nbsp;Annette Bauer-Brandl ,&nbsp;Jef Stappaerts ,&nbsp;Martin Brandl ,&nbsp;Rosanth Vasantharasan ,&nbsp;René Holm","doi":"10.1016/j.ejps.2025.107125","DOIUrl":"10.1016/j.ejps.2025.107125","url":null,"abstract":"<div><div>A recent <em>in vivo</em> study investigated the impact of supersaturation, lipid chain length, and lipase- and precipitation inhibition on the oral absorption of cinnarizine from type I Lipid-based formulations (LBFs). The aim of the current work was to investigate these formulations using the pH-stat lipolysis model, a well-established method for <em>in vitro</em> investigation of LBFs. This method allows the determination of the extent of lipolysis and of the drug distribution during lipolysis. The pH-stat experiment revealed that LBFs containing medium-chain triglycerides (MCT) were digested more than those containing long-chain triglycerides (LCT). Notably, digestion decreased by at least 75 % in the presence of the lipase inhibitor orlistat. XRPD measurements indicated the presence of amorphous cinnarizine upon precipitation. No correlation was found between the drug concentration in the aqueous phase (<em>in vitro</em> area under the curve (AUC)) and the <em>in vivo</em> AUC (R² = 0.022). However, when considering the drug concentration in the micellar phases, a stronger correlation was observed (R² = 0.17), which further improved when only considering MCT-based formulations (R² = 0.85). The poor correlation for LCT-based formulations could be attributed to their poor dispersibility in aqueous media. Overall, an acceptable correlation was found for MCT-based supersaturated formulations considering the drug concentration in the micellar phases. For potential improvement in predictability for supersaturated type I LBFs containing LCT, one will need to discuss whether the observed poor dispersibility in aqueous media is an artefact of the current lipolysis workflow.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"210 ","pages":"Article 107125"},"PeriodicalIF":4.3,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypothalamic connectivity strength is decreasing with polygenic risk in migraine without aura patients","authors":"Anna Németh ,&nbsp;Kinga Gecse ,&nbsp;Dóra Török ,&nbsp;Dániel Baksa ,&nbsp;Dóra Dobos ,&nbsp;Csaba Sándor Aranyi ,&nbsp;Miklós Emri ,&nbsp;György Bagdy ,&nbsp;Gabriella Juhász","doi":"10.1016/j.ejps.2025.107123","DOIUrl":"10.1016/j.ejps.2025.107123","url":null,"abstract":"<div><div>Migraine is a heritable primary headache disorder which pathophysiology involves altered hypothalamic activity during migraine attacks. To explore the relationship between hypothalamic functional connectivity (HYPT FC) and genetic predisposition characterised by polygenic risk scores (PRS), in migraine, this research examines two types of PRS: one based on all migraine patients (PRS_ALL) regardless of their time of diagnosis and other disorders, and another on migraine-first patients (PRS_FIRST), whose first diagnosed condition was migraine in their lifetime. In an independent sample of 35 migraine patients and 38 healthy controls, using resting-state functional magnetic resonance (rfMRI, 3T) brain imaging, the study reveals significant hypoconnectivity of hypothalamus with the two investigated PRS scores but with different brain areas. While weakened hypothalamic connections in relations with PRS_ALL highlight regions involved in pain modulation, correlation with PRS_FIRST emphasizes decreased connections with sensory and integrative brain areas, suggesting a link between migraine-first genetic risk and cortical hyperexcitability. Our results demonstrate that the polygenic risk of different migraine subgroups may advance our insight into the specific genetic and neural underpinnings of migraine, advancing precision medicine approaches in this field.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"210 ","pages":"Article 107123"},"PeriodicalIF":4.3,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Semi-solid extruded tablets for personalized pediatric use: Development, Quality control and In-Vitro Assessment of Enteral Tube Administration","authors":"Mahsa Bahman ,&nbsp;Niklas Sandler Topelius ,&nbsp;Tapani Viitala","doi":"10.1016/j.ejps.2025.107122","DOIUrl":"10.1016/j.ejps.2025.107122","url":null,"abstract":"<div><div>Drug compounding is a common practice in pediatric medication due to limited availability of appropriate dosage forms for children. Semi-solid extrusion (SSE) as a way of 3D printing has shown a substantial potential in personalized medicine for pediatric patients. However, manufacturing tablets through 3D printing is a slow process and might be a bottleneck when many personalized dosages are needed for pediatric use. Here, we use a simplified SSE printing approach for preparing propranolol, spironolactone, and prednisolone tablets (<em>n</em> = 144 of each) with different dosages. The quality control approach for the tablets included the development of HPLC methods for each drug based on their physicochemical properties and investigation of mass and content uniformity, stability, and dissolution. The average dosing accuracy showed good mass uniformity. All the formulations showed an appropriate homogeneity (AV&lt;15) and stability up to 9 months. Dissolution results of the tablets were in compliance with acceptance criteria (USP) for immediate release dosage forms, i.e., 80% of drug released within 45 min. The osmolality of placebo, propranolol, spironolactone, and prednisolone tablets were 86, 81, 78, and 75 mOsm/kg, respectively. These osmolality values were well below the recommended osmolality of pediatric formulations, i.e., &lt; 450 mOsm/kg. Finally, drug recovery tests via nasogastric tube (NGT) were performed with different reconstitution volumes and temperatures. The drug losses varied between 4–36%. The findings of this study suggest that a simplified SSE printing approach is a promising method for manufacturing personalized medicines and can be used to accurately produce tailor-made dosage forms for pediatric patients.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"211 ","pages":"Article 107122"},"PeriodicalIF":4.3,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in suspected adverse drug reactions of anti-seizure medications reported in EudraVigilance","authors":"Michael Magdy Fahmy Girgis ,&nbsp;Gergely Farkasinszky ,&nbsp;Klára Fekete ,&nbsp;István Fekete ,&nbsp;Miklós Vecsernyés ,&nbsp;Ildikó Bácskay ,&nbsp;László Horváth","doi":"10.1016/j.ejps.2025.107119","DOIUrl":"10.1016/j.ejps.2025.107119","url":null,"abstract":"<div><h3>Introduction</h3><div>Epilepsy is one of the most common neurological disorders and requires long-term treatment with anti-seizure medication (ASM) which may cause adverse drug reactions (ADRs). Our aims were to investigate potential sex differences in reporting suspected ADR (sADRs) of ASMs through studying their seriousness, outcomes and Sudden Unexpected Death in Epilepsy (SUDEP).</div></div><div><h3>Methods</h3><div>Using EudraVigilance database, reported sADRs with different ASMs over a ten year period were extracted. List of ASMs was compiled according to Anatomical Therapeutic Chemical Classification System. Reporting Odds Ratio (ROR), 95 % confidence interval (95 % CI), p-value were calculated.</div></div><div><h3>Results</h3><div>In general, more sADRs were reported from females (603,936, 57.46 %). Males showed positive association with the following seriousness criteria: <em>‘life threatening’</em> (ROR=1.02, 95 %CI: 1.01–1.04; <em>p</em> &lt; 0.001), <em>‘caused/prolonged hospitalisation’</em> (ROR=1.06, 95 %CI: 1.05–1.07; <em>p</em> &lt; 0.001), <em>‘results in death’</em> (ROR=1.44, 95 %CI: 1.43–1.46; <em>p</em> &lt; 0.001), and <em>‘congenital anomaly’</em> (ROR=2.43, 95 %CI: 2.41–2.45; <em>p</em> &lt; 0.001). Only with <em>‘not recovered / not resolved’</em> outcome criteria showed negative association in males (ROR=0.72, 95 %CI: 0.70–0.73; <em>p</em> &lt; 0.001), the other outcome criteria demonstrated positive association in the followings: <em>‘fatal’</em> (ROR=1.43, 95 %CI: 1.41–1.45; <em>p</em> &lt; 0.001), <em>‘recovered / resolved’</em> (ROR=1.08, 95 %CI: 1.07–1.09; <em>p</em> &lt; 0.001), <em>‘recovered / resolved with sequelae’</em> (ROR=1.06, 95 %CI: 1.01–1.12; <em>p</em> &lt; 0.001), and <em>‘recovering / resolving’</em> (ROR=1.14, 95 %CI: 1.12–1.15; <em>p</em> &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>Differences were observed between males and females, particularly in terms of seriousness criteria, worse outcomes but prone to recover, and associations with SUDEP to the detriment of males. When choosing an ASM for a patient or especially if the patient has previously experienced an adverse drug reaction. these aspects can also be taken into account and may be important.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"210 ","pages":"Article 107119"},"PeriodicalIF":4.3,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing the performance of electrostatic repulsion-reversed phase chromatography approaches in the resolution of complex peptide mixture: Liraglutide as case study","authors":"Simone Manetto ,&nbsp;Giulia Mazzoccanti ,&nbsp;Michele Bassan ,&nbsp;Marco Macis ,&nbsp;Walter Cabri ,&nbsp;Alessia Ciogli ,&nbsp;Antonio Ricci ,&nbsp;Francesco Gasparrini","doi":"10.1016/j.ejps.2025.107120","DOIUrl":"10.1016/j.ejps.2025.107120","url":null,"abstract":"<div><div>Therapeutic peptides showed an exponentially growth in interest over the course of the last years, in particular those related to the treatment of diabetes and weight control, such as the Glucagon Like Peptide 1 (GLP-1) agonist. Their molecular complexity is however challenging and requires the development of tailored chromatographic analytical tools to efficiently assess their related substance profile. In the present paper, we performed the comparison of two orthogonal approaches related to Electrostatic Repulsion-Reversed Phase (ERRP) chromatography, namely the static ERRP and dynamic ERRP, with the aim to assess their capabilities in terms of resolution. Both the approaches were applied to the GLP-1 derivative Liraglutide as case study, focusing the attention on classical impurities associated with peptide products, such as epimers and endo/eso impurities.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"211 ","pages":"Article 107120"},"PeriodicalIF":4.3,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}