International Journal of Pharmaceutics最新文献

{"title":"A dimensionless framework for hold-up mass prediction and scale transfer in continuous linear blending.","authors":"Ricardo Sousa, Sean Clifford, Ana Costa, Ana Martins, Rita Neves, Artur Saramago, Lukas Dahlgren, João Henriques","doi":"10.1016/j.ijpharm.2026.127570","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.127570","url":null,"abstract":"<p><p>In this work, a dimensionless model is proposed to describe the influence of operating conditions on the hold-up mass (HUM) of a continuous linear blender. The model relates the fill level (normalized hold‑up mass per blender volume) to three key dimensionless groups: a flow-related parameter (χ), the Froude number (Fr), and the number of mixing elements (H). A physically interpretable analytical expression is introduced and calibrated using experimental data across multiple materials and operating conditions. The model demonstrates strong predictive performance, with root mean square errors typically below 5%. Predictions obtained with the intermediate shaft configuration, which was excluded from parameter calibration, demonstrated the model's interpolation capability and calibration robustness. Furthermore, scale transfer was evaluated by calibrating the model using a smaller scale CDC-10 blender and applying it to predict fill level in a larger CDC-50 blender. Comparable prediction errors between calibration and external validation demonstrate the ability of the model to capture the dominant trends governing hold-up behavior across the process conditions studied. In addition, a simplified set of scale transfer rules is derived from the dimensionless framework, showing that maintaining Froude number and χ enables consistent performance across scales. These rules are experimentally validated across a range of formulations and operating conditions, including a real industrial case study. Overall, this work provides a predictive framework to quantify and transfer blending conditions in continuous tableting, supporting more efficient process development and more robust scale transfer.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"127570"},"PeriodicalIF":6.0,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224126","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":"Subcutaneous mesoporous silica formulation modulates systemic and tumor-associated paclitaxel exposure in a B16F10 melanoma model.","authors":"Jihoon Lee, Min-Koo Choi, Sang-Cheol Han, Yong-Il Shin, In Jun Yeo, Im-Sook Song","doi":"10.1016/j.ijpharm.2026.127557","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.127557","url":null,"abstract":"<p><p>Paclitaxel, a widely used chemotherapeutic agent for solid tumors, is primarily administered by intravenous infusion. Although subcutaneous administration has been investigated as a patient-centered alternative, developing subcutaneous paclitaxel formulations remains challenging. In this study, a mesoporous silica nanoparticle-based formulation (PCT112) containing paclitaxel, curcumin, and D-α-tocopheryl polyethylene glycol succinate was developed to modulate systemic and tumor-associated drug exposure after subcutaneous administration. PCT112 showed high encapsulation efficiencies for paclitaxel and curcumin and enabled amorphous drug incorporation within the silica matrix, resulting in sustained release and an increased paclitaxel solubility. In B16F10 melanoma cells, PCT112 showed time-dependent cytotoxicity, increased spheroid uptake, a delayed increase in apoptosis, and more pronounced microtubule disruption than free paclitaxel. In 3-dimensional multicellular tumor spheroids, higher Uptake Index values were associated with greater inhibition of spheroid growth. In B16F10 tumor-bearing mice, repeated subcutaneous administration of PCT112 produced dose-dependent tumor growth suppression and prolonged survival. Pharmacokinetic analysis showed delayed absorption and extended systemic exposure, whereas biodistribution analysis revealed dose-dependent increases in tumor-associated paclitaxel concentrations, which remained detectable over the observation period. Compared with intravenous Abraxane, longitudinal tumor-growth trajectories differed over time, while no statistically significant difference was observed at the final treatment day. Body-weight trajectories differed between the two groups. Collectively, these findings suggest that mesoporous silica-mediated subcutaneous delivery may support a lower-peak, prolonged exposure profile while increasing tumor-associated drug exposure, warranting further preclinical investigation for hydrophobic anticancer agents such as paclitaxel.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"127557"},"PeriodicalIF":6.0,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224102","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 and clinical evaluation of a palatable calcium acetate gummy formulation for patients undergoing hemodialysis.","authors":"Sayuri Kawamoto, Hiroshi Suzuki, Motoyasu Miura, Shimako Tanaka, Yasuharu Kashiwagura, Philip Hawke, Shinji Kageyama, Katsuya Yamauchi, Noriyuki Namiki, Shinya Uchida","doi":"10.1016/j.ijpharm.2026.127569","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.127569","url":null,"abstract":"<p><p>Phosphate binder therapy is essential for managing hyperphosphatemia in patients undergoing hemodialysis. However, nonadherence remains a common challenge. Gummy formulations are considered patient-friendly because they do not require water and are easily chewed. In this study, we developed a calcium acetate gummy formulation (CA-G) and evaluated its pharmaceutical properties and palatability in both healthy volunteers and patients undergoing hemodialysis. CA-G (3.5 g per formulation) was prepared using a gelatin-based matrix containing calcium acetate (CA; 250 mg) and organoleptic masking agents (flavors and sweeteners). The formulation was evaluated for drug content, dissolution behavior, water activity, penetration distance, and phosphate-binding efficacy. Four flavored CA-Gs (yuzu, Darjeeling tea, lemon, and apple) were prepared. In a gustatory sensation test, 24 healthy volunteers evaluated palatability using a 100-mm visual analog scale (VAS). In addition, palatability was assessed by nine patients undergoing hemodialysis using a 5-point scale, and changes in serum phosphate levels were explored. CA content was 102.8% of the intended amount; maximum dissolution rate was 97.6%; water activity was 0.732; and penetration distance was 13.1 mm. Incorporation of CA into the gummy matrix did not compromise maximum phosphate-binding efficacy. Flavored CA-Gs showed significantly higher palatability VAS scores than the non-flavored formulation in healthy volunteers, with at least 75% of patients rating them acceptable. Serum phosphate levels decreased after CA-G supplementation. These findings suggest that palatable and flavor-varied CA-G may represent a patient-friendly dosage-form option for patients undergoing hemodialysis.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"127569"},"PeriodicalIF":6.0,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224063","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 \"Polymeric mixed micellar nanogel enhances dermal delivery and therapeutic efficacy of tofacitinib citrate\" [Int. J. Pharm. 701 (2026) 127154].","authors":"Akanksha Mahajan, Gajanand Sharma, Amita Sarwal, Bhupinder Singh, Om Prakash Katare","doi":"10.1016/j.ijpharm.2026.127524","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.127524","url":null,"abstract":"","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"705 ","pages":"127524"},"PeriodicalIF":6.0,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224047","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 stereolithography 3D printed hollow vaginal devices with pore modulation to tailor the drug release.","authors":"Preethi Lakkala, Siva Ram Munnangi, Nagarjuna Narala, Honghe Wang, Srikanth Baisa, Sateesh Kumar Vemula, Michael A Repka","doi":"10.1016/j.ijpharm.2026.127573","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.127573","url":null,"abstract":"<p><p>Vaginal infections affect nearly 70% of women worldwide at least once in their lifetime, yet conventional therapies remain suboptimal due to short residence time, leakage, and poor patient adherence. Long-acting vaginal systems such as rings and inserts can prolong drug release but are often limited by formulation constraints and the inability to accommodate diverse therapeutic agents. To address these challenges, we developed a novel hollow vaginal device fabricated via stereolithography (SLA) 3D printing using a biocompatible elastic resin. The C-shaped device features two precisely engineered pore openings that enable controlled drug release. Devices with pore diameters ranging from 0.5-2.0 mm were fabricated and loaded with a clindamycin phosphate aqueous gel, a first-line therapy for bacterial vaginosis. Drug release was modulated by the pore diameter and, at a fixed pore diameter, by the gel viscosity, enabling the dose to be adjusted. Mechanical testing confirmed that the elastic structure withstands repeated compression without deformation, ensuring mechanical robustness during vaginal retention. This versatile and customizable platform enables controlled and sustained intravaginal delivery of a wide range of therapeutics, representing a significant step toward patient-centric, next-generation vaginal drug delivery systems.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"127573"},"PeriodicalIF":6.0,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224112","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":"PVA swelling microneedle (PVA-SMNs)-assisted enhancement of tacrolimus ointment penetration for improved psoriasis treatment.","authors":"Min Xu, Xiaoyu Yu, Bo Xu, Bing Zhou, Yan Zhang, Xia Zhang, Huijun Wu, Shuping Hou","doi":"10.1016/j.ijpharm.2026.127555","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.127555","url":null,"abstract":"<p><p>Psoriasis is a common chronic immune-mediated inflammatory skin disease characterized by erythema and scaling, which imposes significant physical and psychological burdens on affected individuals. For facial psoriasis, clinical guidelines recommend tacrolimus (TAC) as an alternative to corticosteroid drugs due to its comparable efficacy and lower risk of adverse effects. However, in severe cases, the excessive proliferation of the stratum corneum leads to thick scales that significantly impede TAC permeation when the ointment is applied directly, resulting in unsatisfactory clinical outcomes. In this study, we propose a combination therapy involving pretreatment with swelling polyvinyl alcohol microneedles (PVA-SMNs) to create microchannels in the skin, followed by TAC ointment application. In vitro permeation tests (IVPT) revealed that PVA-SMNs enhanced the cumulative permeation of TAC by 2.7-fold. Pharmacodynamic studies further demonstrated that this approach significantly reduced the levels of key pro-inflammatory cytokines (IL-17A, IL-23, and TNF-α), which are closely associated with psoriasis pathogenesis. Clinical trials corroborated these findings, providing direct evidence of the efficacy of PVA-SMN-assisted TAC delivery in improving psoriasis treatment. These promising results highlight the potential of this novel combination strategy, which may offer better therapeutic outcomes for psoriasis patients.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"127555"},"PeriodicalIF":6.0,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224075","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":"IVIS assessment of mRNA-LNP protein expression: effects of dosing parameters and prior LNP exposure.","authors":"Rebecca Macfarlane, Burcu Binici, Muattaz Hussain, Ankita Borah, Lee Wheeler, Michael Wilkinson, Natalie Orr, Samuel Clarke, Yvonne Perrie","doi":"10.1016/j.ijpharm.2026.127567","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.127567","url":null,"abstract":"<p><p>Bioluminescence imaging using in vivo imaging systems (IVIS) is widely used to assess reporter protein expression after administration of messenger RNA (mRNA) lipid nanoparticles (LNPs). However, methodological variation and prior LNP exposure can complicate interpretation. Here, we evaluated selected parameters affecting IVIS readouts after intramuscular administration of firefly luciferase mRNA formulated in SM-102 or ALC-0315 LNPs in BALB/c mice. We also investigated the effects of repeated administration. D-luciferin delivery, imaging interval and mouse position influenced signal acquisition, while mRNA dose and injection volume affected the magnitude and regional distribution of expression. Background bioluminescence in mice receiving PBS was negligible compared with mRNA-LNP-associated signals, suggesting that dedicated negative-control groups may be unnecessary once baseline signal is established under consistent imaging conditions. Repeated administration of either SM-102 or ALC-0315 LNPs reduced expression following a subsequent mRNA-LNP dose. This occurred after prior administration of LNPs containing either firefly luciferase mRNA or non-coding polyadenylic acid, whereas repeated PBS injections had no comparable effect. Therefore, the reduced expression was associated with prior exposure to the LNP carrier rather than repeated injection or expression of the encoded reporter. These results highlight the need to standardise IVIS acquisition and dosing parameters, including mRNA dose, injection volume, and administration schedule, and demonstrate that prior LNP exposure can attenuate subsequent mRNA-mediated protein expression.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"127567"},"PeriodicalIF":6.0,"publicationDate":"2026-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220246","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":"Nebulization-stable lipid-polymer hybrid nanoparticles for mRNA delivery in advanced in vitro respiratory models.","authors":"Hiba Hassoun, Camille Pascarel, Alexandra Erny, Elise Giang, Cynthia Garapon, Laetitia Gerossier, Céline Coiffier, Claire Monge, Bernard Verrier, Fabienne Archer, Nicolas Aznar","doi":"10.1016/j.ijpharm.2026.127550","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.127550","url":null,"abstract":"<p><p>Pulmonary delivery of messenger RNA (mRNA) offers a promising strategy for local vaccination and treating respiratory diseases, but aerosolization stress and airway barriers remain major obstacles. Here, we developed PEG-free lipid-polymer hybrid nanoparticles (mucLPs) composed of a solid polylactic acid (PLA) core and an engineered lipid corona. Nine formulations were screened by varying lipid composition and were evaluated for physicochemical properties, mRNA association, cytocompatibility, stability during vibrating-mesh nebulization, and transfection. The lead formulation, mucLP3, combined high mRNA association with a negative post-loading surface charge and preserved its size distribution and reporter activity after nebulization. By contrast, the SM-102-based reference LNP tested under the same conditions showed aggregation and reduced reporter expression after nebulization. Non-nebulized mucLP3 also supported mRNA expression in airway epithelial cell lines, mouse lung organoids, and primary human airway epithelial cultures maintained at an air-liquid interface. These data establish a proof of concept for a PEG-free lipid-polymer hybrid architecture that tolerates the tested nebulization procedure and remains functional in respiratory models of increasing complexity. Direct mucus-transport measurements, aerosol-deposition studies, and in vivo efficacy studies will be required to establish pulmonary delivery performance.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"127550"},"PeriodicalIF":6.0,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216181","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":"Deposition of inhaled aerosols in the human lung: From infancy to adulthood.","authors":"Chantal Darquenne","doi":"10.1016/j.ijpharm.2026.127560","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.127560","url":null,"abstract":"<p><p>This narrative review discusses the effects that healthy aging has on particle deposition in the lungs. The lung structure and its size, breathing patterns and minute ventilation are all affected by age, from infancy through adulthood. These age-dependent variations in turn affect total and regional deposition in the healthy lung. While, for age-specific breathing patterns, overall deposition of inhaled particles tends to be higher in children than in adults, regional deposition is age- and particle size-dependent. For aerosols in the 1-5 µm size range, typical of pharmaceutical aerosols, deposition fraction in the upper respiratory tract is higher in children (<15 year old) than in adults while the opposite is observed in the intrathoracic lungs where deposition fraction is lower in children than in adults. However, compared to adults, children have smaller lung surface area over which the deposited dose is distributed. Consequently, the deposition rate per lung surface area is higher in the intrathoracic lungs of children than of adults. In adulthood, aging appears to have little effect on overall deposition during tidal breathing. However, for deep aerosol inhalation, studies suggest an increased deposition in the lung periphery with aging due to airway closure occurring at higher lung volume in the elderly than in young adults. These observations suggest that both therapeutic aerosol delivery and the adverse effects of particle matter exposure may be altered with age through the lifespan.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"127560"},"PeriodicalIF":6.0,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216210","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":"Bola-amphiphilic dendrimers with tunable architecture for ROS-responsive precision delivery of doxorubicin.","authors":"Dandan Zhu, Shuting Lin, Lingmin Ji, Lei Liu, Manman Wang, Yuanzheng Huang, Shengxiang Liang, Xin Li, Jiaxuan Chen, Yun Li, Chunyong Wu, Shengmei Wu, Ildikó Bácskay, Ferenc Fenyvesi, Xiaoxuan Liu","doi":"10.1016/j.ijpharm.2026.127556","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.127556","url":null,"abstract":"<p><p>Stimuli-responsive nanocarriers capable of precise intracellular drug release are critical for improving the efficacy and safety of cancer chemotherapy. However, many existing systems suffer from limited structural tunability and incomplete integration of molecular architecture, self-assembly, and responsiveness, which constrains tumor delivery and therapeutic performance. Here, we report reactive oxygen species (ROS)-responsive bola-amphiphilic dendrimers with tunable dendron generations, bola4A and bola8A, as a platform for doxorubicin (DOX) delivery and systematic comparison. Both dendrimers displayed high drug-loading capacities and stable nanoassembly formation, whereas bola4A, with lower-generation PAMAM dendrons, permitted more efficient stimulus penetration into the nanosystems. This architectural feature enhanced ROS- and pH-triggered drug release, promoted cellular uptake, and accelerated endosomal escape. Importantly, modulation of dendron generation systematically altered nanoparticle architecture and responsiveness, directly dictating therapeutic efficacy. Consequently, bola4A/DOX nanoparticles achieved superior tumor accumulation and tissue penetration, together with improved anticancer efficacy in vitro and in ovarian cancer SKOV3 xenograft models and reduced systemic toxicity relative to free DOX. These results establish dendritic architecture as a key determinant of stimuli-responsiveness and drug delivery performance, and provide a rational framework for the design of next-generation stimuli-responsive nanomedicines tailored to pathological microenvironments.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"127556"},"PeriodicalIF":6.0,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216188","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}