European Journal of Pharmaceutics and Biopharmaceutics最新文献

{"title":"Structural insights into novel coamorphous systems of azithromycin with faster dissolution profile","authors":"Ilenia D’Abbrunzo ,&nbsp;Ludovica Battaiotto ,&nbsp;Angela Abruzzo ,&nbsp;Giulia Bondi ,&nbsp;Federica Bigucci ,&nbsp;Cinzia Pagano ,&nbsp;Anna Imbriano ,&nbsp;Costanza Fratini ,&nbsp;Luca Casettari ,&nbsp;Dario Voinovich ,&nbsp;Dritan Hasa","doi":"10.1016/j.ejpb.2025.114873","DOIUrl":"10.1016/j.ejpb.2025.114873","url":null,"abstract":"<div><div>In this study, azithromycin, a broad-spectrum antibiotic compound used for the treatment of several bacterial infections, which is characterized by a very low water solubility, was combined with different small molecules to generate more soluble coamorphous solids. The multicomponent systems were prepared through fast precipitation from an ethyl acetate solution, facilitating the formation of amorphous phases in seven azithromycin-based systems. Differential scanning calorimetry confirmed the coamorphous nature in five out of seven systems (i.e., azithromycin–2-, 3-, and 4-aminobenzoic acids, –salicylic acid, –caprylic acid), while two systems (azithromycin–methyl salicylate, –glycerol) exhibited ambiguous thermal behavior. Stability assessments revealed that the homogeneous coamorphous systems remained stable for at least 140 days at 40 °C, while pure amorphous azithromycin, recrystallized within 72 h. The most suitable coamorphous systems were characterized through pair distribution function analysis, providing molecular-level insights into their structural organization. Notably, the azithromycin–caprylic acid system exhibited distinct molecular packing, likely attributable to the unique structural characteristics of its fatty acid-based coformer, which also led to a faster drug dissolution rate compared to the pure crystalline and amorphous azithromycin forms.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"216 ","pages":"Article 114873"},"PeriodicalIF":4.3,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic profiling of macrophages: effects of inflammatory activation and anti-inflammatory treatment with IBD therapeutics","authors":"Simone Lichtner ,&nbsp;Kathrin Schunck ,&nbsp;Johanna Frey ,&nbsp;Janina Osti ,&nbsp;Selina Dannheimer ,&nbsp;Sabrina Schnur ,&nbsp;Claus-Michael Lehr ,&nbsp;Marc Schneider ,&nbsp;Marius Hittinger","doi":"10.1016/j.ejpb.2025.114869","DOIUrl":"10.1016/j.ejpb.2025.114869","url":null,"abstract":"<div><div>Inflammatory bowel diseases (IBD) are chronic disorders characterized by persistent immune dysregulation in the intestinal mucosa, with macrophages playing a central role in disease pathogenesis. In this study, primary human monocyte-derived macrophages (MDMs) were stimulated with lipopolysaccharide (LPS) to model innate immune activation, and subsequent proteomic changes were analyzed by mass spectrometry. The effects of three established IBD drugs, mesalazine, prednisolone and 6-mercaptopurine (6-MP), were systematically evaluated within this model. LPS stimulation resulted in activation of proteins related to pro-inflammatory pathways, including NF-κB signaling, which was reflected by increased expression of cytokine- and adhesion-related proteins such as IL1B, IL8 and ICAM1. Mesalazine treatment induced a moderate modulation of inflammatory regulators, prednisolone produced a strong suppression of pro-inflammatory and complement proteins, and 6-MP caused broad alterations in ribosomal, metabolic and apoptosis-associated proteins. These results indicate that the LPS-stimulated MDM model can reproduce essential features of macrophage activation in IBD and differentiate drug-specific proteomic signatures that are consistent with known mechanisms of action.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"216 ","pages":"Article 114869"},"PeriodicalIF":4.3,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flowrate-Independent indomethacin dry powder inhaler for potential treatment of pediatric asthma: In vitro aerodynamic and anti-inflammatory evaluation","authors":"Nazareth E. Ceschan ,&nbsp;Andrea V. Dugour ,&nbsp;Beatriz Behrend ,&nbsp;Juan M. Figueroa ,&nbsp;Hugh D.C. Smyth ,&nbsp;Verónica Bucalá ,&nbsp;María V. Ramírez Rigo","doi":"10.1016/j.ejpb.2025.114870","DOIUrl":"10.1016/j.ejpb.2025.114870","url":null,"abstract":"<div><div>Asthma, a chronic respiratory condition affecting millions globally, is particularly common in children and a leading cause of emergency visits and hospitalizations. Characterized by airway inflammation and increased bronchial sensitivity, asthma is typically treated with inhaled corticosteroids. Despite their effectiveness, these treatments often face challenges related to adherence and adverse effects. Non-steroidal anti-inflammatory drugs (NSAIDs), though not traditionally used for asthma due to potential adverse reactions in sensitive patients, could be beneficial when administered via inhalation to minimize systemic side effects. In this work, an indomethacin (a NSAID) dry powder inhaler (DPI) is proposed for pediatric asthma treatment as a potential alternative for reducing doses of traditional anti-asthmatic therapies using corticosteroids. Crystalline microparticles, with mean volumetric diameter of 6.0 μm and suitable for inhalation, were obtained by jet-milling, an easy and cost-effective technology. Although the milled particles tended to agglomerate, they were readily dispersed through inhalers with different intrinsic resistances. Under pharmacopoeial conditions (4 KPa), mass median aerodynamic diameter values were 3.7–4.0 μm for inhalers with different intrinsic resistance while aerodynamic particle size distribution was narrow considering GSD was 1.5–1.7. The emitted fraction was high when assays were performed at a 4 KPa pressure drop, but decreased with lower pressure drops in subsequent tests. The fine particle fraction of indomethacin (indicating the emitted amount of drug entering the lungs) was independent of the inspiratory flowrate and inhaler internal resistance, making the formulation suitable for patients with different respiratory capabilities, like children. Finally, milled indomethacin demonstrated an anti-inflammatory effect similar to that of a topical corticosteroid in an asthmatic model.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"216 ","pages":"Article 114870"},"PeriodicalIF":4.3,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Film-forming system of optimized tacrolimus-loaded nanostructured lipid carriers for effective topical treatment of atopic dermatitis","authors":"Jin Sil Kang ,&nbsp;Young-Guk Na ,&nbsp;Minki Jin ,&nbsp;Gabsik Yang ,&nbsp;Dong-Sung Lee ,&nbsp;Jong-Suep Baek ,&nbsp;Hong-Ki Lee ,&nbsp;Cheong-Weon Cho","doi":"10.1016/j.ejpb.2025.114871","DOIUrl":"10.1016/j.ejpb.2025.114871","url":null,"abstract":"<div><div>Tacrolimus (TAC), a calcineurin inhibitor used topically for T-cell-mediated skin diseases, faces challenges due to poor solubility and limited skin penetration. To address these limitations, a film-forming system (FFS) incorporating nanostructured lipid carriers (NLCs) was developed for enhanced topical delivery. TAC-loaded NLCs (TAC-NLC) were prepared via high-temperature and high-pressure homogenization and optimized using Box-Behnken design. The optimized TAC-NLC showed 102.7 nm particle size, 0.126 PDI, 80.5 % encapsulation efficiency, and 2.5 % drug loading. TAC-NLC@FFS demonstrated spherical morphology and improved skin adhesion. In vitro studies showed sustained drug release and reduced cytotoxicity. In a 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis model, TAC-NLC@FFS significantly reduced dermatitis scores compared to the negative control group (score at week 7: 3.5 ± 0.6 vs. 8.00 ± 1.2), with efficacy comparable to commercial ointments. Spleen weight, an indicator of systemic inflammation, was significantly reduced in all treatment groups, supporting anti-inflammatory activity. Additionally, serum IgE and IL-4 levels, key markers of allergic inflammation, were decreased in TAC-treated groups, with IL-4 reduction showing statistical significance. These findings suggest that TAC-NLC@FFS combines improved skin delivery and formulation stability with therapeutic efficacy, offering a promising strategy for the topical treatment of atopic dermatitis.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"216 ","pages":"Article 114871"},"PeriodicalIF":4.3,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Hydroquinone cream-based polymer microneedle roller for the combined treatment of large-area chloasma” [Eur. J. Pharm. Biopharm. 185 (2023) 5-12]","authors":"Yu Ting He ,&nbsp;Yu Ying Hao ,&nbsp;Rui Xing Yu ,&nbsp;Chao Zhang ,&nbsp;Bo Zhi Chen ,&nbsp;Yong Cui ,&nbsp;Xin Dong Guo","doi":"10.1016/j.ejpb.2025.114865","DOIUrl":"10.1016/j.ejpb.2025.114865","url":null,"abstract":"","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"216 ","pages":"Article 114865"},"PeriodicalIF":4.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Towards the development of a standard toolbox for compatibility testing of pediatric drug products with common dosing vehicles − Fruit juice, apple sauce, yogurt, and pudding","authors":"Carolin Eckert ,&nbsp;Cordula Stillhart ,&nbsp;Leonie Wagner ,&nbsp;Emmanuel Scheubel ,&nbsp;Isabelle Prevot ,&nbsp;Marc Lindenberg ,&nbsp;Sandra Klein","doi":"10.1016/j.ejpb.2025.114868","DOIUrl":"10.1016/j.ejpb.2025.114868","url":null,"abstract":"<div><div>Co-administration of oral drug products with dosing vehicles is common practice in pediatric drug administration. The present work focused on the development of a set of standard vehicles that reflects the key characteristics of four different vehicle types commonly used in the administration of pediatric drug formulations. The aim was to rationalize and standardize the compatibility assessment of pediatric dosage forms with individual vehicle types and thereby contribute to a better risk assessment regarding this route of administration. In order to develop the standard vehicles, a comprehensive number of fruit juices, apple sauces, yogurts, and puddings were characterized with regard to their physicochemical properties. The characterization results served as target values for a set of standard vehicles which was successfully developed and followed a design of experiments approach. These standard vehicles represent the first and central components of a standardized vehicle toolbox designed for global use. Their use will enable pharmaceutical developers and regulatory authorities to gain insight into the compatibility of pediatric medicines with these dosing vehicles. Pending validation through comparative studies with the original vehicles, for which data are forthcoming, the toolbox is expected to serve as a valuable resource for assessing the safety and feasibility of combining pediatric formulations with liquid or semi-solid vehicles, thereby supporting more informed decision-making in drug development.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"217 ","pages":"Article 114868"},"PeriodicalIF":4.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation and characterization of different extraction methods for obtaining extractable and leachable materials from rubber stopper systems used in pharmaceutical products","authors":"Yasin Gökekin ,&nbsp;Mehmet Bulut ,&nbsp;Büşra Çetin Ersen ,&nbsp;Müge Güleli ,&nbsp;Cem Çalışkan","doi":"10.1016/j.ejpb.2025.114844","DOIUrl":"10.1016/j.ejpb.2025.114844","url":null,"abstract":"<div><div>Bromobutyl rubber stoppers are widely used in the primary packaging systems of many different drug products. However, different additives are added to provide the existing properties of these synthetic elastomeric stoppers. The most important additives are curing agents, activators, plasticizers, fillers, antioxidants and accelerators. However, these components are not covalently bonded to the polymer chains and have the potential to leach from the rubber stopper material to the drug product during its shelf life. Therefore, since they may adversely affect the product’s safety, efficacy and stability, they should be identified and monitored through extractable studies. In addition, regulatory authorities such as the US Food and Drug Administration (US FDA) and the European Medicines Agency (EMA) require the submission of Extractables and Leachables (E&amp;L) information to examine the risks. For this purpose, E&amp;L originating from bromobutyl rubber stoppers was examined within the scope of the study. Two different sample preparation methods were used to extract volatile, semi-volatile and non-volatile components at the highest level. The microwave assisted extraction methods, which are relatively widely used and provide faster and less solvent consumption than Soxhlet and also provide longer and continuous contact with the packaging matrix, were compared with the conventional Soxhlet extraction method. The results show that the number of components obtained by microwave assisted extraction method is higher. In addition, different solvent environments (IPA + water, pH 3.5 solution and pH 9.5 solution) were used to expose the matrix to extreme conditions to obtain non-volatile components. The extractable components obtained were identified by using the library databases of the relevant gas chromatography-Mass Spectrometry (GC–MS) and liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF) analytical devices. Elemental impurities were quantitatively determined by inductively coupled plasma mass spectrometry (ICP-MS) and evaluated within the scope of possible additives. In addition, six different drug product formulations using bromobutyl rubber stoppers in container-lid systems were investigated within the scope of leachable studies. The results show that the presented methodology is successful in the E&amp;L analysis of different therapeutic products. Moreover, it is adaptable to the analysis of different primary packaging products to ensure product quality and patient safety, while also offering a new approach to E&amp;L analysis for both the literature and the pharmaceutical industry.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"216 ","pages":"Article 114844"},"PeriodicalIF":4.3,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Payload-dependent photostability of antibody-drug conjugates","authors":"Carl Oliver Thiess ,&nbsp;Karsten Mäder ,&nbsp;Hanns-Christian Mahler ,&nbsp;Steffen Wöll","doi":"10.1016/j.ejpb.2025.114867","DOIUrl":"10.1016/j.ejpb.2025.114867","url":null,"abstract":"<div><div>Antibody-Drug Conjugates (ADCs) are nowadays an important therapeutic modality. The (cytotoxic) payload, being the drug, is herewith conjugated to an antibody, which provides targeting. Whilst a lot of attention for technical characterization and stress testing often focuses on the antibody piece, there has been little attention for the payload. Hence, the present study compared the photostability of model ADCs with different payloads, chosen to be representative for the main payload classes used in current clinical and commercial ADC products (Auristatins (MMAE), Maytansinoids (DM1) and Camptothecins (Exatecan)). After photodegradation, the stability of ADCs was evaluated for sizing and charge differences, as well as presence of reactive oxygen species (ROS). Out of the three tested ADCs and the native mAb, the Exatecan-conjugated ADC exhibited the strongest photodegradation, demonstrated by strong coloration, increase in aggregate levels up to ∼ 8.5 % in size-exclusion HPLC, and a change in charge profile leading to a decrease in ion-exchange chromatography peak height to 27 % compared to unstressed samples. Additionally, strong presence of ROS was demonstrated only in samples containing Exatecan-ADC and Exatecan drug-linker. As the analyzed ADCs only vary in the conjugated payload, and the unconjugated mAb remained stable during forced photodegradation, our results indicate that Exatecan acts as a strong photosensitizer. This finding is different from photodegradation of monoclonal antibodies, in which proteinogenic photosensitizers such as tryptophan are typically responsible for photodegradation. Therefore, companies developing ADCs should –apart from the antibody framework<em>–</em> also focus their attention on the payload and how it plays a role in stress-related degradation pathways.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"216 ","pages":"Article 114867"},"PeriodicalIF":4.3,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fabrication and in-depth analysis of a novel-hybrid TPGS phytosome system for enhanced anti photoaging efficacy of grape seed extract","authors":"Hanan Refai ,&nbsp;Mona Elhabak ,&nbsp;Doaa H. Hassan ,&nbsp;Omar S. Ahmed ,&nbsp;Esraa M. Mohamed ,&nbsp;Heba S. Rateb ,&nbsp;Nesrine S. El Sayed ,&nbsp;Mariam K. Ahmed ,&nbsp;Pierre Waffo-Téguo ,&nbsp;Josep Valls ,&nbsp;Nermeen Z. Abuelezz","doi":"10.1016/j.ejpb.2025.114843","DOIUrl":"10.1016/j.ejpb.2025.114843","url":null,"abstract":"<div><div>Photoaging is a widespread skin health concern caused by UV radiation. It significantly contributes to premature wrinkles and exacerbates further skin damage. This study evaluates the enhanced anti-aging efficacy of a nano phytosome incorporating grape seed extract (GSE) as an innovative, naturally driven antiaging formula, demonstrating putative skin permeability. LC-HRMS analysis and molecular docking revealed the potential of GSE components against photoaging targets. A GSE-nano phytosome formula with phosphatidyl choline (PC)/GSE ratio of 50:1 and 10 mg Vitamin E TPGS displayed optimal physicochemical properties, including particle size (195.1 ± 0.4 nm), polydispersity index (0.312 ± 0.015), zeta potential (25.6 ± 0.4 mV), and complexation efficiency (76.2 ± 4.5 %). FTIR analysis confirmed the formation of hybrid phytosomes through complexation with PC and TPGS. <em>ex vivo</em> confocal microscopy displayed enhanced skin permeability. Biochemical studies confirmed the superior antiaging effect of GSE-phytosome(GSE-nanogel) compared to crude GSE in UV-irradiated rats. GSE nanogel promoted anti-aging by suppressing c-Jun N-terminal kinase (JNK) and NF-κB, caspase-3, enhancing GSH-Px level and reducing malondialdehyde level. These effects suppressed elastase and collagenase activity, significantly improving wrinkles and skin redness. Our findings underscore the efficiency of formulating high molecular weight GSE phytoconstituents as phytosomes that mimic the lipophilic nature of cell membranes, improve skin permeability, and therapeutic efficacy.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"216 ","pages":"Article 114843"},"PeriodicalIF":4.3,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Supersaturation of self-nanoemulsifying drug delivery systems: Correlation between equilibrium solubility and supersaturation concentration, effect on droplet size and impact of polymer addition","authors":"Rui Peng ,&nbsp;Anette Müllertz ,&nbsp;Jacob Bannow ,&nbsp;Thomas Rades","doi":"10.1016/j.ejpb.2025.114862","DOIUrl":"10.1016/j.ejpb.2025.114862","url":null,"abstract":"<div><div>Supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS) have emerged as a promising approach to increase the drug load of hydrophobic molecules, compared to conventional SNEDDS (con-SNEDDS). This study aimed to explore the relationship between equilibrium solubility (S_eq) and the maximum supersaturation concentration (CS_max) in SNEDDS preconcentrates for three model drugs: carvedilol (CVL), ritonavir (RTV) and nilotinib (NTB). The emulsion droplet size of con-SNEDDS (90 % of S_eq) and super-SNEDDS (90 % of CS_max), and the influence of polyvinylpyrrolidone-vinyl acetate copolymers 64 (PVP/VA 64) was assessed, as well as the relationship between physical stability and viscosity of super-SNEDDS in the presence of PVP/VA 64. A Design of Experiment (DoE) approach was applied to optimize SNEDDS compositions. The results showed linear correlations between S_eq and CS_max across all three model drugs, leading to a consistent (but drug dependent) maximum degree of supersaturation (DS_max) (CVL = 2.49, RTV = 4.56, NTB = 2.54) within the DoE design space. Dissolving 4 % (w/w) PVP/VA 64 in the SNEDDS preconcentrates did not influence the described correlations or DS_max. Emulsion droplet size remained unchanged upon drug loading to 90 % of S_eq (con-SNEDDS) compared to drug-free SNEDDS. Further loading to 90 % of CS_max (super-SNEDDS) also resulted in negligible size changes in emulsions with initial droplet sizes below 60  nm, whereas those above 60  nm exhibited pronounced droplet size increase, following a quadratic relationship compared with their initial con-SNEDDS droplet size. Incorporation of PVP/VA 64 enhanced both the physical stability and viscosity of super-SNEDDS; however, only a weak correlation was observed between these two parameters, suggesting that viscosity alone did not govern the stabilization of super-SNEDDS. In summary, within the design space, DS_max is drug-dependent, but independent of SNEDDS composition or polymer addition; droplet size of super-SNEDDS is dependent on both drug and SNEDDS composition, but is unaffected by polymer; in contrast, physical stability is jointly influenced by drug properties, SNEDDS composition, and polymer addition.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"216 ","pages":"Article 114862"},"PeriodicalIF":4.3,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}