European Journal of Pharmaceutical Sciences最新文献

{"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}

{"title":"Characterization of digital camera-based UV illumination fluorescent imaging for concentration measurement with limit of detection, specificity and precision","authors":"Bettina Fazekas,&nbsp;Dorina Gréta Pogány,&nbsp;Dorián László Galata,&nbsp;Zsombor Kristóf Nagy,&nbsp;Lilla Alexandra Mészáros,&nbsp;Edit Hirsch","doi":"10.1016/j.ejps.2025.107117","DOIUrl":"10.1016/j.ejps.2025.107117","url":null,"abstract":"<div><div>Nowadays the increased need for pharmaceutics requires fast, cheap and reliable quality control systems to investigate the final product’s quality. The generally used methods like high-pressure liquid chromatography (HPLC) and other coupled techniques are not just time-consuming but also expensive and often destructive. To facilitate real-time measurement of active ingredient concentration, an alternative non-destructive machine vision and artificial intelligence-based system was tested, that implements ultraviolet (UV) illumination. With this technique the concentration of the active pharmaceutical ingredient containing fluorophore groups can be studied due to the different light emission of the different active pharmaceutical ingredient concentrations. However, to facilitate the practical application of this novel non-destructive and system, it is essential to determine its limit of detection (LoD) and limit of quantification (LoQ). In this study we aimed to study the LoD and LoQ of UV illumination fluorescent imaging of tablets using levofloxacin as the active pharmaceutical ingredient. We also execute intermediate precision and specificity studies to gather more information about the reliability of this novel technique.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"210 ","pages":"Article 107117"},"PeriodicalIF":4.3,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143928592","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":"Asialofetuin-Coupled Lipid-Based nanosystems to target the Asialoglycoprotein receptor: Delivering genes to hepatocytes for the treatment of Fabry disease","authors":"Julen Rodríguez-Castejón ,&nbsp;Paula Fernández-Muro ,&nbsp;Marina Beraza-Millor ,&nbsp;María Ángeles Solinís ,&nbsp;Alicia Rodríguez-Gascón ,&nbsp;Ana del Pozo-Rodríguez","doi":"10.1016/j.ejps.2025.107118","DOIUrl":"10.1016/j.ejps.2025.107118","url":null,"abstract":"<div><div>Exploiting the protein production capacity of hepatocytes for <em>de novo</em> expression of α-Galactosidase A (α-Gal A) by gene supplementation therapy represents one of the most promising strategies for the treatment of Fabry disease (FD). The asialoglycoprotein receptor (ASGPr) has proven to be one of the target receptors of choice for hepatocyte-directed nanomedicines, and natural glycoproteins such as asialofetuin (AF) can be used as specific ligands. Herein, we have developed AF-decorated solid lipid nanoparticles (SLNs), prepared by different techniques and cationic lipid compositions, for restoring the enzyme deficiency in FD by gene supplementation targeted to hepatocytes. After the physicochemical characterization of the vectors, cell association and transfection efficacy were evaluated in vitro in human hepatocytes (Hep G2), and the capacity to increase α-Gal A activity was evaluated in vivo after intravenous administration to α-Gal A knockout mice. The efficacy and targeting effect were conditioned by the type of SLN. In general, vectors containing a mixture of the cationic lipids DOTAP and DODAP showed enhanced transfection efficacy compared to their counterparts without DODAP. The incorporation of AF in the vectors formulated with SLNs prepared with DOTAP and DODAP by hot-melt emulsification significantly improved the efficacy to induce the expression of α-Gal A in hepatocytes in vitro compared to the control without AF. However, the administration to Fabry mice did not result in a significant increase in enzyme activity. The lack of <em>in vitro-in vivo</em> correlation corroborates the need to understand key factors influencing the behavior of non-viral vectors in biological media for nucleic acid therapies, as well as the desirability of in vivo studies in the early stages of pharmaceutical development of nucleic acid delivery systems.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"210 ","pages":"Article 107118"},"PeriodicalIF":4.3,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916209","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":"Probabilistic design space exploration and optimization via bayesian approach for a fluid bed drying process","authors":"Qingbo Meng,&nbsp;David Bogle,&nbsp;Vassilis M. Charitopoulos","doi":"10.1016/j.ejps.2025.107116","DOIUrl":"10.1016/j.ejps.2025.107116","url":null,"abstract":"<div><div>The concept of Design Space (DS), delineated as a region of investigated variables aimed at maintaining product quality, was introduced in the International Conference on Harmonisation (ICH) Q8 as a framework to direct pharmaceutical development. However, the complexity of processes and the presence of uncertainties in pharmaceutical manufacturing exacerbate the difficulties of exploring a reliable and robust DS. This study investigates the probabilistic design space to explain the process operability and performance reliability using a Bayesian approach for a fluid bed drying process. We initially develop a Bayesian model by integrating a surrogate-based predictive model with embedded uncertainty quantification of material variability. Subsequently, employing a grid search-based technique to discretize the operational variable domain facilitates the exploration of the probabilistic DS to meet the specified product quality requirements. Meanwhile, optimization is employed to obtain the maximum DS region and enhance its operability. Results demonstrate that the Bayesian approach is an effective method to identify a probability DS to guarantee product quality at the desired reliability level considering material and process uncertainty.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"210 ","pages":"Article 107116"},"PeriodicalIF":4.3,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935502","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":"Mathematical modelling of thermal interactions during freezing: Effects on product morphology and drying behaviour","authors":"Vincenzo Massotti,&nbsp;Fiora Artusio,&nbsp;Antonello A. Barresi,&nbsp;Roberto Pisano","doi":"10.1016/j.ejps.2025.107112","DOIUrl":"10.1016/j.ejps.2025.107112","url":null,"abstract":"<div><div>Freeze-drying of biopharmaceuticals is a crucial operation to increase their stability and shelf-life. Parenteral drug products are generally frozen in vials placed in contact with a temperature-controlled shelf. Uncontrolled nucleation is a source of batch heterogeneity, as nucleation occurs at different temperatures in vials frozen at different times. Heat released from a vial undergoing solidification may be transferred to neighbouring vials, impacting their thermal profiles and altering the distribution of the nucleation temperature and the freezing rate within the batch. This study characterised thermal coupling in interacting and non-interacting loading configurations. These estimations were used as input in a simple 1D mathematical model to assess the effect of thermal interactions on the freeze-dried product morphology. Thermal interactions strongly impacted the predicted nucleation temperature, especially for late-nucleating vials, and the freezing rate. The combined effect of thermal coupling on nucleation temperature and freezing rate resulted in different frozen product morphology. Heterogeneity within a batch of interacting vials was higher compared to non-interacting vials, leading to broader pore size and drying time distributions, in agreement with experimental data. The presented model provides insight into the thermal history of each vial of the batch during freezing, supporting the rational design of freezing processes.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"210 ","pages":"Article 107112"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143928593","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":"How to proceed with easily recrystallizing secnidazole in designing polyelectrolyte complex-based films for periodontitis treatment?","authors":"Joanna Potaś-Stobiecka ,&nbsp;Radosław A. Wach ,&nbsp;Karolina Jurkiewicz ,&nbsp;Anna Basa ,&nbsp;Magdalena Wróblewska ,&nbsp;Katarzyna Winnicka","doi":"10.1016/j.ejps.2025.107115","DOIUrl":"10.1016/j.ejps.2025.107115","url":null,"abstract":"<div><div>Secnidazole is a second generation 5-nitroimidazole with high potential for application in anaerobic periodontal infections therapy. In this study, the process of developing the drug-loaded films composed of oppositely charged chitosan and pectin for intra-pocket administration is presented. Due to limitations of layer-by-layer technique in receiving systems of this type, which resulted from spontaneous crystallization of secnidazole at the stage of drying, a new preparation method was developed. For this purpose, drug cocrystallization technique as well as two-step drying procedure were implemented in order to minimize secnidazole crystals growth during solvent evaporation. Through visual assessment, mechanical strength measurements and scanning electron microscopy imaging, the most promising secnidazole-chitosan cocrystals-loaded films were selected for further physicochemical (via differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray powder diffraction, optical microscopy) and pharmaceutical (in vitro release, antimicrobial and swelling tests) analyses. The impact of utilized polymeric composition and polyelectrolyte complex structures as well as secnidazole form (crystalline/amorphous) on the films performance was observed. The increased temperature of drying enhanced secnidazole-polymers miscibility, which resulted in desirable drug loading improvement and also significantly prolonged secnidazole release to the artificial saliva.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"209 ","pages":"Article 107115"},"PeriodicalIF":4.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898932","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":"Testing on continuous production of mefenamic acids—Design of experiment through simulation and process optimisation","authors":"Kai Eivind Wu ,&nbsp;Cameron J. Brown ,&nbsp;Murray Robertson ,&nbsp;Blair F. Johnston ,&nbsp;Rhys Lloyd ,&nbsp;George Panoutsos","doi":"10.1016/j.ejps.2025.107102","DOIUrl":"10.1016/j.ejps.2025.107102","url":null,"abstract":"<div><div>In the pharmaceutical manufacturing industry, continuous production methods have been recognised as providing several benefits compared to traditional batch production. These benefits include increased flexibility, higher product output, enhanced quality assurance through better monitoring techniques, and more consistent distribution of Active Pharmaceutical Ingredients (APIs). Despite these clear advantages, there is a lack of research focused on the simultaneous optimisation of multiple sub-processes in continuous manufacturing. This study explores the optimisation processes of continuous pharmaceutical production, explicitly targeting the production of mefenamic acid using wet milling (WM) and mixed-suspension mixed-product removal (MSMPR). We employ data-driven evolutionary optimisation algorithms to address these many-objective optimisation problems (MaOPs). High-fidelity model-generated data generated via the General Process Modelling System (gPROMS) is subsequently utilised to develop simpler surrogate models based on the Radial Basis Function Neural Network (RBFNN). This enables very fast simulations, suitable for use with computationally intensive machine learning algorithms. Utilising evolutionary optimisation algorithms, these models are used for model-based process optimisation. The efficacy of the MaOP approach is evaluated using a range of numeric and visual optimisation performance indicators. Our findings underscore the viability of integrating high-fidelity and surrogate models to discern functional relationships between dependent variables (objective functions) and independent variables (decision variables), providing a robust framework for process optimisation within the pharmaceutical domain. The approximated solutions are, on average, 58% better than the solutions obtained from Latin hypercube sampling. The chosen optimal solutions can form the basis of parameter setting in upcoming experimental campaigns. The significance of this work is in the demonstration, for the first time, of a many-objective optimisation framework for continuous pharmaceuticals production using simple surrogate models derived from high fidelity simulations using Machine Learning.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"210 ","pages":"Article 107102"},"PeriodicalIF":4.3,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143928569","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":"Antibody oxidation and impact of formulation: A high-throughput screening approach","authors":"Paulina Fischer ,&nbsp;Olivia M. Merkel ,&nbsp;Michael Siedler ,&nbsp;Tanja Meyer ,&nbsp;Lucienne Nouchikian ,&nbsp;Martin Huelsmeyer","doi":"10.1016/j.ejps.2025.107113","DOIUrl":"10.1016/j.ejps.2025.107113","url":null,"abstract":"<div><div>Oxidation is a complex degradation pathway in biopharmaceutical products that necessitates comprehensive assessment to ensure product stability and safety. This study focuses on implementing an oxidative profiling workflow within a high-throughput (HT) formulation screening process to identify and mitigate potential oxidation liabilities. To assess the feasibility of integrating oxidative stress testing into HT formulation development, we analyzed the oxidation susceptibility of three monoclonal antibodies by varying several formulation parameters including protein concentration, buffer system and pH, surfactant type and concentration as well as presence of antioxidative excipients. Oxidative stress was induced using visible light, hydrogen peroxide, and metal-catalyzed oxidation. HT analytical methods such as Size Exclusion Chromatography and Reversed-Phase Chromatography subunit analysis were employed to assess aggregation and modification of Fc and Fab subunits. An oxidation scoring tool was developed to simplify the evaluation of large datasets. The results demonstrated that formulation composition can significantly influence oxidation susceptibility. However, the outcomes varied greatly among the different antibodies, highlighting the need for a comprehensive profiling approach. The study confirms that the oxidation profiling workflow is an effective method for routine HT formulation screenings, providing a thorough evaluation of the oxidative stability of biopharmaceutical formulations.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"209 ","pages":"Article 107113"},"PeriodicalIF":4.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904322","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}