Simon Drescher, Giuseppe De Rosa, Jai Prakash, Félix Sauvage, Philipp Uhl, Richard Wibel
{"title":"Special Issue: Phospholipids as Functional Ingredients in Pharmaceutical Formulations: Current Advances and Perspectives.","authors":"Simon Drescher, Giuseppe De Rosa, Jai Prakash, Félix Sauvage, Philipp Uhl, Richard Wibel","doi":"10.1016/j.ejps.2025.107334","DOIUrl":"https://doi.org/10.1016/j.ejps.2025.107334","url":null,"abstract":"","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":" ","pages":"107334"},"PeriodicalIF":4.7,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336496","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}
Elżbieta Czarniewska, Ewa Mijowska, Klaudia Zielinkiewicz, Katarzyna Rolle, Dariusz Wawrzyniak
{"title":"Influence of 3-, 4- and 6-layered borophene on biocompatibility with \"non-professional\" human phagocytes.","authors":"Elżbieta Czarniewska, Ewa Mijowska, Klaudia Zielinkiewicz, Katarzyna Rolle, Dariusz Wawrzyniak","doi":"10.1016/j.ejps.2025.107335","DOIUrl":"https://doi.org/10.1016/j.ejps.2025.107335","url":null,"abstract":"<p><p>The medical application of borophene in fields such as in vivo diagnosis, drug delivery, and photochemical therapy of cancer requires detailed assessment. There is no knowledge about its effects on cells, organs, and the whole organism of humans and animals. It can be assumed that the impact of borophene on cells will be correlated with the aspect ratio of the 2D flakes and their thickness. This study sought to determine if these nanomaterials are biocompatible and, if not, whether their cytotoxicity is caused by their thickness, dosage, or exposure duration in the model cells employed in the study. The influence of 3-, 4- or 6-layer borophene in the concentration range from 0.2 to 1 mg/ml of the medium on the morphology, integrity of the cell membrane, induction of apoptosis and reactive oxygen species and the level of reducing power in MRC-5 cells was investigated. The study showed no effect of borophene on the plasma membrane, no cytotoxic effects leading to apoptosis or necrosis of MRC-5 cells even at high doses of tested nanomaterials and regardless of the number of layers. Borophene had a beneficial effect on human fibroblasts because it increased or did not change the level of reducing power, which balanced of oxidative stress in cells, if induced. These effects allowed maintaining cell viability and functionality. This study opens up research perspectives leading to understanding the mechanisms responsible for maintaining viability in the borophene-exposed cells. The question remains whether borophene is biocompatible in other models, e.g., non-phagocytic cells, and what other molecular mechanisms are involved in maintaining the viability of the borophene-exposed cells. If the biocompatibility of borophene with a wide range of cells is confirmed, it will find numerous applications in biomedicine with special emphasis on Boron Neutron Therapy.</p>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":" ","pages":"107335"},"PeriodicalIF":4.7,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336438","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}
M.M. Said , A.M. Braam , E. Duijvelaar , J.R. Schippers , L. Atmowihardjo , J. Twisk , H.J. Bogaard , E.L. Swart , J. Aman , I.H. Bartelink
{"title":"Exposure-response analysis of oral and intravenous imatinib in critically ill patients with COVID-19 acute respiratory distress syndrome","authors":"M.M. Said , A.M. Braam , E. Duijvelaar , J.R. Schippers , L. Atmowihardjo , J. Twisk , H.J. Bogaard , E.L. Swart , J. Aman , I.H. Bartelink","doi":"10.1016/j.ejps.2025.107332","DOIUrl":"10.1016/j.ejps.2025.107332","url":null,"abstract":"<div><h3>Introduction</h3><div>Imatinib, initially approved for chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST), was investigated in two randomized placebo-controlled trials for its potential effect on COVID-19-related ARDS (C-ARDS). A known relationship between imatinib concentrations and effectiveness exists in CML and GIST, but this is uncharacterized in critically ill C-ARDS patients, where standard dosing may not be suitable.</div></div><div><h3>Aims</h3><div>This study aims to explore the association between unbound imatinib, total imatinib, and total N-desmethyl-imatinib exposure with clinical outcomes in critically ill C-ARDS patients.</div></div><div><h3>Methods</h3><div>This post-hoc analysis included C-ARDS patients from the CounterCOVID and InventCOVID trials, all requiring invasive ventilation. In the CounterCOVID trial, patients received 800 mg imatinib on day 1, followed by 400 mg once daily for 9 days. In InventCOVID, the dose was 200 mg intravenously twice daily for 7 days or until ICU discharge. A pharmacokinetic (PK) model simulated the concentration-time profiles of total imatinib (T), unbound imatinib (U), and the sum of total imatinib plus its metabolite desmethyl-imatinib (PM). PK samples were used to estimate individual PK parameters, after which associations with clinical outcomes (WHO score, P/F ratio, ICU stay, ventilator-free days, and mortality) were tested using linear mixed models and regression analysis.</div></div><div><h3>Results</h3><div>Data from 53 patients revealed that critically ill patients reached higher total imatinib exposure but similar unbound imatinib exposure compared to others. Critical illness and concurrent treatments influenced imatinib exposure. No clear exposure-response relationship was found between imatinib exposure and clinical outcomes.</div></div><div><h3>Conclusion</h3><div>Although critical illness was linked to higher imatinib exposure, no exposure-response relationship was found. Disease severity may have also impacted the drug’s effectiveness, suggesting that ICU patients may require adjusted dosing. Future clinical studies of repurposed drugs should focus on exposure-response relationships to better understand optimal dosing in new patient populations, particularly for highly protein-bound drugs.</div></div><div><h3>Trial Registration</h3><div>ClinicalTrials.gov Identifier: NCT04794088, registered 11 March 2021. European Clinical Trials Database (EudraCT number: 2020-005447-23).</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"215 ","pages":"Article 107332"},"PeriodicalIF":4.7,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318236","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":"Mapping the ABC Transporter Landscape in the Human Lung: A Comprehensive Characterisation of P-gp, MRP1 and BCRP Expression and Functional Activity in Human Lung Epithelial Cells.","authors":"Sina Simon, Thanusa Shanmugalingam, Tobias Neu, Nicole Schneider-Daum, Carina Cantrill, Claus-Michael Lehr","doi":"10.1016/j.ejps.2025.107333","DOIUrl":"https://doi.org/10.1016/j.ejps.2025.107333","url":null,"abstract":"<p><p>Active efflux transporters can play a substantial role in the drug disposition of their substrates in the human body. Efflux transporters like P-glycoprotein (P-gp), multidrug resistance associated protein 1 (MRP1) and breast cancer resistance protein (BCRP) were described to be expressed in the human lung. However, there is conflicting data reported regarding their expression and functional activity in the human lung epithelium in vitro. In this study, the expression and functional efflux of P-gp, MRP1 and BCRP was investigated in cell lines and primary cells derived from human upper (16HBE14o-, Calu-3, NHBE) and lower airways (NCI-H441, A549, hAELVi, Arlo and hAEpC). Additionally, the impact of culture condition, air liquid interface (ALI) vs liquid covered condition (LCC), on transporters' expression levels and efflux was evaluated. Gene and protein expression analysis revealed a ubiquitous expression of MRP1, while BCRP was present in most cells, except Calu-3, Arlo and hAEpC and P-gp was absent in all cells apart from Calu-3. Culturing the cells at ALI vs. LCC condition had only a significant impact on P-gp and MRP1 protein expression levels in Calu-3, which were both reduced at LCC. The functional activity of the expressed efflux transporters was demonstrated by the intracellular accumulation of fluorophore substrates in absence and presence of transporter specific inhibitors. However, bidirectional transport studies using drug substrates did not result in any observed efflux mediated by MRP1 and BCRP across any of the lung epithelial cells. Only P-gp, expressed in Calu-3 at ALI, showed functional activity in this experimental setting. In addition, it was observed that not all tested cells are suitable for studying pulmonary drug disposition processes in vitro due to their inability to form a tight cell barrier. Overall, the results of this study indicate differences in drug transporters' expression levels across human lung epithelial cells. Moreover, the efflux of model fluorophores for P-gp, MRP1 and BCRP was determined, whereas no such efflux was observed for MRP1 and BCRP when using drugs as substrates.</p>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":" ","pages":"107333"},"PeriodicalIF":4.7,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145328493","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}
Quanwu Sun , Shenhan Yu , Rong Shi, Meng Xu, Peilan Ma, Feng yan Lv
{"title":"Synergistic chemoimmunotherapy using pirarubicin-loaded tumor-derived extracellular vesicles for triple-negative breast cancer (TNBC)","authors":"Quanwu Sun , Shenhan Yu , Rong Shi, Meng Xu, Peilan Ma, Feng yan Lv","doi":"10.1016/j.ejps.2025.107331","DOIUrl":"10.1016/j.ejps.2025.107331","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) has an extremely poor clinical prognosis due to the lack of effective therapeutic targets and high heterogeneity. In this study, we developed a synergistic chemoimmunotherapy based on tumor-derived extracellular vesicles (TEVs), which induces immunogenic cell death (ICD) and remodels the immunosuppressive tumor microenvironment (TME) by delivering pirarubicin (THP). 4T1 TNBC cell derived TEVs were loaded with THP via overnight co-incubation at room temperature (THP@TEVs), which exhibited excellent tumor targeting and biocompatibility. In vitro experiments demonstrated that THP@TEVs was efficiently internalized by tumor cells, and compared to the free THP group, THP@TEVs significantly increased the apoptosis rate (70.25 % vs. 25.61 %, <em>p</em> < 0.001, <em>n</em> = 3)”. In vivo studies showed that THP@TEVs significantly activated the ICD effect and promoted CD8⁺ T-cell infiltration by enhancing calreticulin (CRT) membrane translocation and high mobility group protein B1 (HMGB1) release (CRT increased≈3 fold; HMGB1 increased≈3.1 fold). In addition, compared with the control group, the tumor volume in the THP@TEVs group was reduced by approximately 62.1 % (<em>p</em> < 0.001, <em>n</em> = 5) and no histopathological changes were observed in major organs (such as heart, liver, spleen, lungs, and kidneys) upon H&E staining. This study provides a precise, low-toxicity chemotherapy and immune synergistic strategy for TNBC and expands the potential of TEVs in tumor therapy.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"215 ","pages":"Article 107331"},"PeriodicalIF":4.7,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312744","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}
Júlia Tárnoki-Zách , Imre Boldizsár , Gábor M. Kovács , Balázs Döme , Szilvia Bősze , András Czirók
{"title":"Characterizing solute transport across cell layers: Artifact correction and parameter extraction from a simplified three-compartment model","authors":"Júlia Tárnoki-Zách , Imre Boldizsár , Gábor M. Kovács , Balázs Döme , Szilvia Bősze , András Czirók","doi":"10.1016/j.ejps.2025.107323","DOIUrl":"10.1016/j.ejps.2025.107323","url":null,"abstract":"<div><div>Quantifying solute transport across epithelial cell layers grown on transwell inserts is a common approach in early-stage drug development to estimate pharmacokinetic properties such as absorption and bioavailability. To increase throughput and reduce variability, these assays are increasingly automated, including the use of robotic or microfluidic systems for time-resolved sampling. However, both automated and manual sampling can introduce systematic artifacts, such as residual volume retention and surface adsorption, that distort concentration time series and affect downstream analysis. To fully realize the potential precision of automated measurements, we propose a mathematical correction to account for sampling artifacts; then, to fit the corrected data to a three-compartment model that captures membrane diffusion, cellular sequestration, and metabolic loss. The method is demonstrated on datasets from transwell epithelial barrier transport assays. We suggest that the considered three-compartment model yields mechanistically more meaningful parameters than the conventional apparent permeability (Papp) measure. The proposed approach thus enables more accurate characterization of analyte interactions with the barrier cell layer, supporting better-informed assessments of compound behavior in vitro transport systems. Quantifying solute transport across epithelial cell layers grown on transwell inserts is a common approach in early-stage drug development to estimate pharmacokinetic properties such as absorption and bioavailability. To increase throughput and reduce variability, these assays are increasingly automated, including the use of robotic or microfluidic systems for time-resolved sampling. However, both automated and manual sampling can introduce systematic artifacts, such as residual volume retention and surface adsorption, that distort concentration time series and affect downstream analysis. To fully realize the potential precision of automated measurements, we propose a mathematical correction to account for sampling artifacts; then, to fit the corrected data to a three-compartment model that captures membrane diffusion, cellular sequestration, and metabolic loss. The method is demonstrated on datasets from transwell epithelial barrier transport assays. We suggest that the considered three-compartment model yields mechanistically more meaningful parameters than the conventional apparent permeability (Papp) measure. The proposed approach thus enables more accurate characterization of analyte interactions with the barrier cell layer, supporting better-informed assessments of compound behavior in vitro transport systems.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"215 ","pages":"Article 107323"},"PeriodicalIF":4.7,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307274","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}
Stephanie Ramos, Marina Vignes, Philippe-Henri Secretan, François-Xavier Legrand, Maxime Annereau, Bernard Do
{"title":"HYBRID GPP-HOSPITAL CONTROL STRATEGY FOR SEMI-SOLID EXTRUSION 3D PRINTING OF ONC201 CHEWABLE UNITS IN PEDIATRIC ONCOLOGY.","authors":"Stephanie Ramos, Marina Vignes, Philippe-Henri Secretan, François-Xavier Legrand, Maxime Annereau, Bernard Do","doi":"10.1016/j.ejps.2025.107326","DOIUrl":"https://doi.org/10.1016/j.ejps.2025.107326","url":null,"abstract":"<p><p>Children with central nervous system tumors often face significant barriers to age-appropriate medicines, especially when dysphagia prevents the use of conventional tablets or capsules. ONC201 (dordaviprone), a first-in-class imipridone available in France under a compassionate access program, poses additional challenges of poor solubility and chemical instability. Chewable formulations offer an attractive solution for pediatric compliance, but their development requires robust pharmaceutical and regulatory controls to ensure safety, stability, and reproducibility. We describe a hybrid GPP-hospital control strategy for semi-solid extrusion (SSE) three-dimensional printing of ONC201 chewable units. In this model, an ONC201 hydrogel intermediate is prepared centrally in a Good Preparation Practices (GPP)-compliant unit under Quality by Design (QbD) specifications and subsequently distributed to hospital pharmacies for on-demand personalization. Patient-ready chewable units are produced locally under in-process controls (IPCs) that monitor extrusion, geometry, unit weight, disintegration, and drug content. Formulation screening and batch characterization identified a stable ONC201 hydrogel suitable for decentralized use, with a conservative refrigerated shelf-life of 14 days. Printed chewable units demonstrated consistent quality attributes and rapid drug release, meeting pharmacopeial expectations for immediate release dosage forms. By combining centralized QbD-controlled preparation with decentralized hospital-based personalization, this work establishes a transferable framework for safe, traceable, and patient-adapted delivery of ONC201 in pediatric oncology, complementing ongoing clinical investigations.</p>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":" ","pages":"107326"},"PeriodicalIF":4.7,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307298","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":"Corrigendum to “Enhanced intracellular uptake of an albumin fusion protein in cancer cells by its forced cell surface recruitment” [European Journal of Pharmaceutical Sciences 191 (2023) 106591]","authors":"Daisuke Kurimoto, Atsushi Sato","doi":"10.1016/j.ejps.2025.107319","DOIUrl":"10.1016/j.ejps.2025.107319","url":null,"abstract":"","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107319"},"PeriodicalIF":4.7,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291453","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}
Ali Hallaj, Gwenaël Labouèbe, Virginie Mansuy-Aubert, Evgeniya Trofimenko, Christian Widmann
{"title":"Monitoring endosomal escape of fluorescent cell-penetrating peptides","authors":"Ali Hallaj, Gwenaël Labouèbe, Virginie Mansuy-Aubert, Evgeniya Trofimenko, Christian Widmann","doi":"10.1016/j.ejps.2025.107330","DOIUrl":"10.1016/j.ejps.2025.107330","url":null,"abstract":"<div><div>Cell-penetrating peptides (CPPs) have the capacity to transport cargos into cells either through endocytosis or direct translocation across the plasma membrane. CPPs entering via endocytosis remain generally trapped within endosomes and lysosomes. This entrapment can be alleviated by coupling the CPPs to endosomal escape promoting cargos or by using small molecules that permeate endosomes or lysosomes. L-Leucyl-L-Leucine methyl ester (LLOMe) is an example of such a molecule.</div><div>The assessment of CPP endosomal escape into the cytosol is not trivial as cytosolic acquisition can also occur via CPP direct translocation across the plasma membrane. Moreover, visualization of CPP cytosolic acquisition often requires the CPP to be tagged with a fluorophore that can affect the behavior of the CPP and that can also be released from the CPP in the degradative environment of endosomes and lysosomes. In the present work, we have explored various parameters that can potentially affect the recording of CPP endosomal escape, such as the chirality of the amino acids making the CPPs, the nature of the fluorophore coupled to the CPPs, and the timing of the recording. For this purpose, we have used three commonly used CPPs: R9 (a synthetic CPP made of 9 arginines), TAT, and penetratin. We have used LLOMe as the endosomal escape promoter.</div><div>This study presents guidelines for the assessment of CPP endosomal escape. We also provide a framework for selecting appropriate combinations of amino acid chirality, fluorophore type, and assessment timing based on what researchers want to achieve when the CPP-cargo is released from vesicles into the cytosol.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"215 ","pages":"Article 107330"},"PeriodicalIF":4.7,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307325","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":"Advanced investigation of the suitability of confocal Raman spectroscopy for dermatological bioequivalence assessments using caffeine and 1,2-pentanediol","authors":"Annette Gaiser, Dominique Lunter","doi":"10.1016/j.ejps.2025.107324","DOIUrl":"10.1016/j.ejps.2025.107324","url":null,"abstract":"<div><div>Since the European Medicines Agency released its “Guideline on quality and equivalence of locally applied, locally acting cutaneous products”, the interest in bioequivalence studies especially in relation to the approval of generics has grown. The guideline provides a framework for the methodology of such studies with the specification of tape stripping as the sole method for skin penetration tests and the vague requirements for a control formulation presenting slight shortcomings in this context. Thus, the aim of this study was to broaden the understanding of what constitutes a suitable control formulation as well as showing the suitability of confocal Raman spectroscopy (CRS) as an alternative method to tape stripping. Validation of CRS results was achieved by performing tape stripping and CRS experiments using caffeine as a model API consecutively on the same skin samples. In order to investigate a suitable control formulation, the effect of different concentrations of 1,2-pentanediol as a penetration enhancer on thermodynamic activity and thus penetrated API amount was examined. We established that CRS is appropriate for both quantitative skin penetration testing as well as in depth bioequivalence testing by demonstrating that the findings of tape stripping and CRS were extremely similar in terms of both the total amounts of detected API as well as the outcomes of bioequivalence testing. Furthermore, we could show that high concentrations of 1,2-pentanediol, by improving the solubility of caffeine, reduce the thermodynamic activity sufficiently to obtain a suitable control formulation. Lower concentrations achieved the expected penetration enhancement but not to a sufficient degree that the formulation can be used as a control. Finally, against the background of these findings, the penetration-enhancing effect of 1,2-pentanediol was investigated, whereby effects on the lipid structure of the stratum corneum and a water-binding effect in the skin were observed.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"215 ","pages":"Article 107324"},"PeriodicalIF":4.7,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299287","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}