International Journal of Pharmaceutics最新文献

{"title":"Effective process for screening melanin binding affinity of small molecule drugs and new drug candidates.","authors":"Pekka Vanhanen, Mika Reinisalo, Tatu Lajunen, Stanislav Kalinin, Jari Leskinen, Arto Urtti","doi":"10.1016/j.ijpharm.2026.126964","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.126964","url":null,"abstract":"<p><p>Melanin binding of small molecule drugs can lead to targeted disposition to the pigmented tissues and prolonged pharmacological responses in the eye. Melanin binding of drugs in vitro correlates with in vivo binding, but current workflows for binding affinity require multiple slow steps, and analytical method development, and/or they may result in high data variability. We developed tangential flow filtration-based methodology to produce size-specific fractions of water-soluble melanin nanoparticles (MNPs), reducing production time from 2-3 days to just a few hours and yielding MNPs with enhanced fluorescence signal. Improved MNPs enabled modifications to a previously published microscale thermophoresis-based melanin binding protocol, shifting analytical focus toward thermophoretic behavior, reducing data variability, and improving reproducibility. The process was tested with nine compounds with varying melanin binding affinities, and the results were consistent with literature, confirming the ability of the method to differentiate compounds based on melanin binding. Fast and reliable workflow will be useful in screening binding affinity for therapeutics and new drug candidates to melanin thereby facilitating ocular drug discovery and construction of predictive pharmacokinetic simulation models.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126964"},"PeriodicalIF":5.2,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856224","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":"Nano-in-micro dry powder formulations combining azithromycin and menadione as adjuvant against pulmonary P. aeruginosa infections.","authors":"Kristela Shehu, Janina Osti, Marius Hittinger, Annette Kraegeloh, Marc Schneider","doi":"10.1016/j.ijpharm.2026.126965","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.126965","url":null,"abstract":"<p><p>Chronic lung infections caused by Pseudomonas aeruginosa are a major contributor to morbidity and mortality in patients with cystic fibrosis. Biofilm formation and the emergence of antibiotic resistance limit the effectiveness of current inhaled therapies, highlighting the need for innovative formulation strategies that enhance local antibacterial efficacy while preserving epithelial integrity. This study explores a nano-in-micro inhalable formulation design that combines azithromycin (AZM) with the antibiotic adjuvant menadione (MEN) to enhance antibiofilm activity under biorelevant pulmonary exposure conditions. Nano-embedded microparticles (NEMs) were developed as an inhalable \"Trojan particle\" approach, combining AZM in a microparticle matrix with MEN-loaded polymeric nanoparticles. The formulations were produced by spray drying and characterized in terms of morphology, aerodynamic performance, solid-state properties and redispersibility. Antibiofilm activity against P. aeruginosa biofilms and epithelial safety in Calu-3 cells were evaluated using biorelevant aerosol exposure models, including nebulization and dry powder atomization. NEMs exhibited favorable aerodynamic properties suitable for bronchial delivery. Incorporation of MEN into the NEM system enhanced the antibiofilm efficacy of AZM compared with the microparticle matrix-only formulation, indicating that the adjuvant effect of MEN was retained upon translation into an inhalable formulation. Cytotoxicity studies demonstrated that neither nebulized nor dry powder-delivered formulations compromised the membrane integrity of Calu-3 cells. These results indicate that the combination of azithromycin and menadione within a NEM design preserves drug activity and adjuvant efficacy while enabling effective aerosol delivery. Future studies in more complex and disease-relevant models will further strengthen the understanding of the translational potential of this approach.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126965"},"PeriodicalIF":5.2,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837734","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":"API particle size governs in situ forming implant formation, microstructure evolution and performance.","authors":"McKenzie Roy, Xiaoyi Wang, Zhifang Hao, Ruifeng Wang, Yan Wang, Bin Qin, Qi Li, Qiangnan Zhang, Diane J Burgess","doi":"10.1016/j.ijpharm.2026.126951","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.126951","url":null,"abstract":"<p><p>In situ forming implants (ISFIs) are long-acting injectable (LAI) drug delivery systems that undergo phase inversion upon contacting an aqueous environment, resulting in the formation of a semisolid-solid implant. To date, six ISFI products are commercially available, four of which are suspension-based formulations. Despite their growing clinical use, no generic ISFI products have reached the market. This underscores the need to better understand their complex behavior and to elucidate the critical quality attributes (CQAs) that govern their performance. While relationships between polymer physicochemical properties (e.g., molecular weight, lactic-to-glycolic acid ratio, end-group chemistry) and release kinetics have been extensively explored, the influence of the active pharmaceutical ingredient (API) remains insufficiently defined. To fill this knowledge gap, the present study investigates a risperidone ISFI that is qualitatively and quantitatively (Q1/Q2) equivalent to the commercial product Perseris®. Previous work has shown that Q1/Q2 equivalence alone does not ensure equivalent performance in vitro and in vivo, prompting the need to investigate additional formulation attributes. The current work focuses on evaluating the impact of API particle size and morphology on implant formation and in vitro release behavior. Thus, formulations containing risperidone with different particle sizes were prepared and evaluated. Subsequently, implant microstructure, water uptake, polymer degradation, and drug release were extensively characterized. A novel aspect of this work is the application of multiple imaging strategies, including laser scanning confocal microscopy (LSCM) for surface imaging and an adhesive thin-film technique for internal imaging, enabling detailed investigation of the evolution of microstructural differences between formulations. The findings highlight the importance of API particle size in governing implant microstructure, water uptake, polymer degradation, and in vitro release behavior, providing insight that will support the development of future generic and innovator ISFI products.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126951"},"PeriodicalIF":5.2,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837740","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":"Amino acid derivatives and surfactants as multifunctional excipients for overcoming drug solubility and permeability challenges.","authors":"K S Surabhi, Srinatha Anegundha, B K Sridhar","doi":"10.1016/j.ijpharm.2026.126946","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.126946","url":null,"abstract":"<p><p>Amino acid derivatives and surfactants are gaining increased application in formulation design due to their unique properties such as biocompatibility and ability to form molecular interactions. This review delves into the emerging role of amino acid derivatives for improving drug solubility and permeability challenges, assessing their mechanisms and potential in formulation design. Drug solubility is enhanced by amino acid derivatives and surfactants through several mechanisms such as micelle formation, ion pairing, and hydrotropy, while the transcellular uptake, transporter activation, and prodrug formation enhance permeability. The article summarizes the scope of Gemini amino acid-based surfactants (AAGSs), which have lower critical micelle concentration (CMC), higher solubilization, strong surface activity, better bioavailability and improved stability due to their advanced dimeric amphiphilic features. Beyond solubility and permeability enhancement, future research may aim at optimizing amino acid derivatives for targeted delivery, exploring synergistic effects with nanotechnology, including smart surfactants, nanocarrier systems and targeting neurodegenerative diseases. Overall, amino acid-based systems offer a promising platform for circumventing bioavailability limitations.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126946"},"PeriodicalIF":5.2,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837737","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":"Design and formulation strategies to modulate drug release from implantable devices.","authors":"Elizabeth R Magill, Masoud Adhami, Octavio Fandino, Yujie Lu, Juan Domínguez-Robles, Eneko Larrañeta","doi":"10.1016/j.ijpharm.2026.126947","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.126947","url":null,"abstract":"<p><p>Implantable drug delivery systems (IDDSs) provide an attractive alternative for delivering drugs locally or systemically in a sustained manner. They offer a promising therapeutic option for patients with chronic conditions that traditionally rely on continuous drug administration via oral or injectable routes. Achieving these benefits, however, depends critically on the selection of materials and excipients used in the preparation of IDDSs. This review focuses on preformed solid IDDSs and how their design and formulation strategies can be adapted to optimise drug release. A wide range of aspects, such as implant design and formulation strategies, are explored. The review provides a comprehensive discussion of conventional formulation approaches adapted for IDDSs, including solubility enhancement, polymer degradation, porosity modulation, particle size reduction, and the incorporation of micro- or nano-encapsulation strategies. In addition, design parameters such as implant geometry and the use of rate-controlling membranes are discussed in detail. The article emphasises the importance of integrating advances in disciplines such as polymer science, manufacturing technologies, and drug formulation into the design of preformed IDDSs. Future directions emphasise personalised implant design, smart materials, and multi-drug delivery systems to address evolving clinical needs.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126947"},"PeriodicalIF":5.2,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837649","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":"Nanocarrier and probe strategies for nuclear targeting.","authors":"Merve Inel, Ayse Yildirim, Bahadir Ozturk, Mustafa Yilmaz","doi":"10.1016/j.ijpharm.2026.126945","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.126945","url":null,"abstract":"<p><p>Nuclear targeting probes and nanocarriers remain limited in the literature, highlighting a critical gap in subcellular targeting strategies. This review outlines four key strategies for delivering probes and drugs to the cell nucleus. Active targeting with peptides, aptamers, and proteins enables precise nuclear import and supports real-time mapping of epigenetic activity. Cationic molecules bind DNA via charge-based and structural compatibility, while nanoparticle size is tuned to bypass nuclear pores after tumor accumulation. Nuclease-resistant, peptide-conjugated, and light-responsive carriers improve nuclear delivery by avoiding degradation and lysosomal trapping. Lipid-based and aptamer-guided systems bring therapeutics close to genomic DNA, with stimuli like acidity or light enabling controlled release. Carbon and gold nanostructures showcase how these strategies improve nuclear access and therapeutic impact. Overall, effective designs align delivery methods with biological barriers and quantify nuclear targeting efficiency, advancing nucleus-focused diagnostics and treatments.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126945"},"PeriodicalIF":5.2,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837678","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":"Predicting plasma concentration-time profiles of orally disintegrating tablets with delayed absorption under fed conditions without water.","authors":"Yui Oyabu, Toshihide Takagi, Shinji Yamashita, Fumiyoshi Yamashita","doi":"10.1016/j.ijpharm.2026.126931","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.126931","url":null,"abstract":"<p><p>Orally disintegrating tablets (ODTs) offer substantial advantages for patients with swallowing difficulties; however, under fed conditions without water, ODTs frequently exhibit delayed absorption, complicating pharmacokinetic evaluation and Bioequivalence (BE) assessment. In particular, unpredictable prolongation of T_max necessitates excessively dense and prolonged blood sampling in BE studies, increasing ethical and economic burdens on study participants and sponsors. To address this challenge, we developed a novel framework to predict plasma concentration-time profiles with delayed absorption under this dosing condition. Absorption-delay functions were derived from published individual plasma concentration-time profiles of rivaroxaban ODTs using a numerically stable, matrix-based non-negative least-squares deconvolution method. These functions were applied by convolution to simulate without-water plasma concentration-time profiles using the corresponding individual-level with-water profiles. In addition, to overcome the limited availability of individual-level data, we developed a Gaussian process-based generative model that reconstructs realistic individual profiles using only reported means and standard deviations of plasma concentration data. The proposed framework accurately reproduced observed profiles of multiple rivaroxaban ODT formulations and demonstrated transferability to ODTs containing different active ingredients, including tolvaptan and sildenafil. Predicted T_max and C_max values were consistent with reported data. This framework provides a practical and quantitatively grounded basis for predicting delayed absorption of ODTs administered under fed conditions without water and for the rational design of sampling schedules in BE studies, enabling more effective, cost-efficient, and patient-friendly study designs.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126931"},"PeriodicalIF":5.2,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837660","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":"A 3D-printed diffusion cell for nail permeation testing.","authors":"Stanislas Maisonneuve, Sandy Vrignaud, Marc Pihet, Frédéric Lagarce, Sylvie Crauste-Manciet, Brice Calvignac, Vincent Lebreton","doi":"10.1016/j.ijpharm.2026.126898","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.126898","url":null,"abstract":"<p><p>Evaluation of nail diffusion of active pharmaceutical ingredients (API) is a challenge but a necessity during pre-clinical studies of antifungals for the treatment of onychomycosis. Nevertheless, available model are expensive or poorly accessible. Thus, a model based on a 3D printable cell and bovine hoof slices was designed. This model was assessed with two Amphotericine B (AmB) based preparations, a gel and a cream. After 7 days diffusion in the 3D printed cell, AmB was extracted from the hooves slices and quantitated by high-performance liquid chromatography (HPLC). Obtained AmB mean concentrations in hooves were 125.9 ± 7.4 µg/cm³ for AmB gel and 95.6 ± 15.9 µg/cm³for AmB cream, with \"cm³\" referring to hoof thickness multiplied by diffusion surface. To complete the hoof diffusion test in the 3D printed cell, agar diffusion was also performed to access the ability of the API to diffuse through a water based matrix and to keep its antifungal properties. An ungual penetration model, using a 3D printed diffusion cell, that is simple to implement and easily accessible has been developed. Although it cannot produce results directly extendable to humans, it allows the comparison of several semi-solid formulation solutions with each other.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"698 ","pages":"126898"},"PeriodicalIF":5.2,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837665","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":"Effect of drug solubility, polymer, and filler on drug release from modified-release matrix tablets in hydroethanolic media.","authors":"Tobias Heinrich, Roland Bodmeier, Andriy Dashevskiy","doi":"10.1016/j.ijpharm.2026.126940","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.126940","url":null,"abstract":"<p><p>This study aimed to develop strategies to prevent accelerated drug release (alcohol-induced dose dumping) from modified-release matrix tablets in hydroethanolic media. Drugs with different solubility profiles (theophylline, propranolol HCl, paracetamol, and carbamazepine) were formulated with water-soluble or water-insoluble matrix formers, with optional addition of soluble or insoluble fillers. Drug release, medium uptake, and leaching were evaluated in 0.1 N HCl containing 0, 20, or 40% (v/v) ethanol. No release acceleration was observed for theophylline and propranolol HCl, which showed low solubility ratios between hydroethanolic and aqueous media (approximately 2). In contrast, paracetamol and carbamazepine (solubility ratio approximately 20) required formulation adjustments. For paracetamol, comparable release profiles across media were achieved using matrix formers with low medium uptake (e.g., Klucel® MXF or Kollidon® SR) or by incorporating a soluble filler such as lactose. For carbamazepine, the increased solubility in hydroethanolic media shifted the release mechanism from erosion-dominated to diffusion-dominated; similar release profiles were only obtained with hydrophilic polymers exhibiting relatively high erosion rates.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126940"},"PeriodicalIF":5.2,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837655","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":"Development of UV-cured captopril-loaded ink for pharmaceutical 3D printing by custom-built SSE extruder.","authors":"Marta Kozakiewicz-Latała, Paweł Krzaczkowski, Wiktoria Śnietura, Julia Brożyna, Hanna Czapor-Irzabek, Malwina Brożyna, Katarzyna Malec, Bożena Karolewicz","doi":"10.1016/j.ijpharm.2026.126930","DOIUrl":"10.1016/j.ijpharm.2026.126930","url":null,"abstract":"<p><p>It is widely acknowledged that conventional dosage forms are frequently not adequately customized to meet the specific clinical requirements of individual patients, what induces the need to process existing dosage forms to improve comfort and patient compliance. This phenomenon is especially evident in pediatric and geriatric populations, where there is a shortage of adequate doses of medication or where a difficulty is reported in their administration. Personalized soft gel-based dosage forms offer a viable solution to the problems associated with the administration of solid forms, especially in special needs populations. One of the most promising technologies that has the potential to facilitate personalization and the production of soft dosage forms is three-dimensional printing (3DP) using the semi-solid extrusion (SSE) method. This method allows the processing of low melting point materials and colloidal materials, e.g. gels and pastes. In this study, a light-curable gel (ink) was designed using a polyethylene glycol diacrylate (PEGDA) as a base polymer. Riboflavin and L-arginine were used as photoinitiators, demonstrating that it is possible to fabricate UV-cured gels without the need for potentially toxic ingredients such as triethylamine, or TPO/DPPO commonly used in this type of formulations. The model drug incorporated into the ink was captopril, which primary indication is the treatment of hypertension and heart failure. The possibility of using an individualized approach to its dosing could reduce the risk of adverse effects, particularly in elderly or pediatric patients. For the 3D printing process of soft dosage forms SSE extruder designed by the authors has been used. Demonstrative version of extruder can be installed in commercial FDM (Fused Deposition Modeling) printers which enables the execution of a considerable number of experiments using a variety of gels under controlled laboratory conditions, without the need for a significant financial investment. In a final experiment, a series of donut-shaped tablets were printed from the designed ink, which exhibited immediate drug release (over 80% within 30 min). Additionally, in this study an interesting phenomenon observed was improvement in polymerization of API-incorporated ink, what based on NMR spectra analysis may be explained by beneficial influence of captopril structure itself and its thiol group on cross-linking process progress. Summarizing, an ink composition formulated in the presented project that contains non-toxic photoinitiators and co-initiators can be utilized in an innovative self-assemble SSE extruder compatible with FDM commercial 3D printer, with optional UV-curing system.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126930"},"PeriodicalIF":5.2,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837692","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}