Journal of pharmaceutical sciences最新文献

{"title":"Evaluating the impact of in-line PES filters on subvisible particle formation during IV administration of IgG4 monoclonal antibody","authors":"Praval Shah,&nbsp;Maria Fischer,&nbsp;Taylour Treadwell ,&nbsp;Sandipan Sinha ,&nbsp;Kai Zheng","doi":"10.1016/j.xphs.2026.104161","DOIUrl":"10.1016/j.xphs.2026.104161","url":null,"abstract":"<div><div>Intravenous (IV) administration is a common delivery route for protein therapeutics, especially when used for oncology indications. Typically, multiple components, including IV bags with diluents and infusion sets, are used for IV administration, where proteins encounter various surfaces and materials, leading to potential physical and chemical degradations. Thus, it is important to evaluate the compatibility of the drug product with IV diluents, and IV administration sets to ensure product quality. In this study, when the compatibility of an IgG4 monoclonal antibody was assessed for two kinds of infusion sets after diluting in IV bags containing 0.9% sodium chloride, an increase in subvisible particles was observed post-infusion through one of the sets. Both infusion sets equipped with in-line PES filters with the same pore size (0.2 µm) and similar nominal filtration area (10 cm²), except for the shape of the filter (rectangular vs cylindrical). To understand the cause of increases in subvisible particles post infusion, a thorough assessment was conducted to evaluate the potential impact of infusion rate, infusion set tubing, in-line filter (particle shedding, location, contact surface area of the filter), and polysorbate 20 concentration in the drug product formulation. The results showed that the pore structure and contact surface area of the filter have an impact on surfactant adsorption which can lead to subvisible particle formation. The results from this study underscores the importance of conducting thorough in-use compatibility studies with different infusion materials during formulation development to identify an appropriate level of surfactant, which can mitigate the risk of subvisible particle formation during IV infusion.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 3","pages":"Article 104161"},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959484","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":"Direct analysis of subvisible particles in pharmaceutical drug products with non-invasive Mie-Scattering light sheet technology: profiling inherent particle growth in monoclonal antibody solutions","authors":"Benjamin Laccetti ,&nbsp;Mingshu Liang ,&nbsp;Monica Goss ,&nbsp;Changhuei Yang ,&nbsp;Shawn Cao","doi":"10.1016/j.xphs.2026.104170","DOIUrl":"10.1016/j.xphs.2026.104170","url":null,"abstract":"<div><div>Enumerating and sizing subvisible particles (SbVP) is an important aspect of ensuring pharmaceutical drug product (DP) quality. Existing SbVP characterization is limited by the destructive nature of testing methods and the need to withdraw solution from DP primary containers. Mie-Scattering light sheet (MSLS) SbVP analysis, a technology that measures scattering from a sheet of light projected directly through a DP primary container, has the potential to address these shortcomings. MSLS testing has previously been demonstrated on solutions of homogeneous polystyrene (PS) beads in standard DP vials. Proteinaceous SbVP inherent to DP biologics have heterogeneous size distribution, aspherical morphology, and lower optical contrast than bead standards. In the work described herein, the MSLS analyzer’s ability to enumerate and size proteinaceous SbVP was evaluated. Use cases were developed to assess how proteinaceous SbVP suspended in solutions of monoclonal antibody (mAb) can be analyzed after exposure to agitation and storage with varied formulation pH. Measurement variability was assessed on scan-to-scan and container-to-container basis across the full functional range of the system (10 to 300,000 particles/mL). Results show the MSLS analyzer successfully elucidated SbVP growth dynamics while preserving the DP sample, enabling direct assessment of product stability. The sensitivity, working range, and accuracy of the MSLS analyzer for characterizing inherent particles were also presented, and future development direction discussed.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 3","pages":"Article 104170"},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046319","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":"Reply to Maboudi’s comment on “Formulation and in vitro evaluation of liposomal and SMEDDS-based cannabidiol delivery systems”","authors":"Chrystalla Protopapa ,&nbsp;Ioannis Tsichlis ,&nbsp;Siva Satyanarayana Kolipaka ,&nbsp;Dennis Douroumis ,&nbsp;Costas Demetzos ,&nbsp;Marilena Vlachou","doi":"10.1016/j.xphs.2026.104174","DOIUrl":"10.1016/j.xphs.2026.104174","url":null,"abstract":"","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 3","pages":"Article 104174"},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146086177","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":"2026 Editorial Advisory Board (EAB) appointments and updates","authors":"Kenneth L. Audus","doi":"10.1016/j.xphs.2025.104132","DOIUrl":"10.1016/j.xphs.2025.104132","url":null,"abstract":"","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 3","pages":"Article 104132"},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800615","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":"Modeling and simulation of benzimidazole dissolution behavior in different monosolvents using machine learning and thermodynamic models","authors":"Kassem AL Attabi ,&nbsp;Farag M.A. Altalbawy ,&nbsp;Deepak J ,&nbsp;Anupama Routray ,&nbsp;Karthikeyan A ,&nbsp;Harjot Singh Gill ,&nbsp;Yashwant Singh Bisht ,&nbsp;Rafid Kamal Jameel ,&nbsp;Ahmed Aldulaimi ,&nbsp;Rafid Jihad Albadr ,&nbsp;Mariem Alwan ,&nbsp;Abdolali Yarahmadi Kandahari","doi":"10.1016/j.xphs.2025.104137","DOIUrl":"10.1016/j.xphs.2025.104137","url":null,"abstract":"<div><div>Benzimidazole, a compound valued for its distinct physicochemical characteristics and diverse applications, is the focus of this investigation into its dissolution behavior across various monosolvents. This research employs sophisticated machine learning algorithms, including K-nearest neighbors (KNN), ensemble learning (EL), random forest, decision tree, and adaptive boosting, alongside thermodynamic models such as Apelblat, λh, NRTL, and Margules, to model and predict solubility. A detailed dataset consisting of 171 experimental points, where 136 are used for training and 35 for testing, was curated to encompass 19 monosolvents, including water, methanol, ethanol, n-propanol, isopropanol, n-butanol, 2-butanol, isobutanol, n-pentanol, acetonitrile, acetone, 2-butanone, 1,4-dioxane, methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, isobutyl acetate, and butyl acetate. The models utilized key input variables including monosolvent type, monosolvent molar mass (g/mol), and temperature (K) which significantly govern Benzimidazole’s solubility. Sensitivity analysis conducted via Monte Carlo simulations identified monosolvent type as the most influential parameter, followed by temperature and monosolvent molar mass, with sensitivity values of 4.28439, 3.54761, and 2.958176, respectively. The dataset underwent thorough validation to ensure its robustness for data-driven modeling. Model performance assessments demonstrated that adaptive boosting achieved superior predictive precision, yielding the highest R² values and the lowest RMSE and AARE percentages across training and test datasets. These findings emphasize the effectiveness of machine learning, especially adaptive boosting, in providing accurate and efficient solubility predictions. The developed machine learning framework provides an economical complement to experimental methods, facilitating rapid and cost-effective prediction of solubility behavior.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 3","pages":"Article 104137"},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145810163","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":"2026 Editorial Advisory Board (EAB) appointments and updates.","authors":"Kenneth L Audus","doi":"10.1016/j.xphs.2025.104132","DOIUrl":"https://doi.org/10.1016/j.xphs.2025.104132","url":null,"abstract":"","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 3","pages":"104132"},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147348753","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":"Stability of therapeutic monoclonal antibodies during infusion with elastomeric pumps intended for home-based therapy","authors":"Elham Taherian ,&nbsp;Mirjam Crul ,&nbsp;Reza Nejadnik","doi":"10.1016/j.xphs.2026.104159","DOIUrl":"10.1016/j.xphs.2026.104159","url":null,"abstract":"<div><div>The majority of monoclonal antibodies (mAbs) are administered through intravenous infusion, typically in hospitals. A shift towards home-based therapy, initially driven by the COVID-19 pandemic, has been underway in recent years. Elastomeric pumps are devices that can be used for home-based therapy. They have been used for analgesics and antibiotics but not for delicate APIs such as proteins. While there is interest in using elastomeric pumps for administration of mAbs, and a few reports indicate that some hospitals have already started using them, valid stability data are lacking. This study aimed to investigate the stability of two marketed antibodies, Erbitux (cetuximab) and Herzuma (trastuzumab), during infusion using an elastomeric pump. High-performance size exclusion chromatography (HPSEC), flow imaging microscopy (FIM), dynamic light scattering (DLS), UV-VIS spectroscopy, and nanoparticle tracking analysis (NTA) were employed to assess subvisible particles and aggregation. Results show high stability and no degradation in form of aggregation in HPSEC. FIM data revealed that particle counts were the same before and after infusion using the pump. DLS and NTA data exhibited uniform particle sizes across samples, suggesting undetectable aggregation. Overall, findings support the technical feasibility of utilizing this combination of elastomeric pump and conditions for administration of cetuximab and trastuzumab, providing valuable insights into maintaining product stability outside traditional healthcare settings.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 3","pages":"Article 104159"},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959593","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":"A comprehensive discussion on analytical method development and validation of a USP type-IV dissolution method for dexamethasone in a combination ophthalmic suspension with povidone-iodine","authors":"Likhit Mandal ,&nbsp;Dr. Praveen Kumar Vemuri","doi":"10.1016/j.xphs.2026.104165","DOIUrl":"10.1016/j.xphs.2026.104165","url":null,"abstract":"<div><div>Antimicrobial resistance resulting from the widespread use of topical antibiotics has accelerated the need for non-antibiotic strategies in ocular therapy. Povidone-iodine (PVP-I) offers broad antimicrobial activity without inducing resistance, while dexamethasone provides potent anti-inflammatory effects, making their combination a promising ophthalmic suspension for infectious and inflammatory conditions. To ensure therapeutic consistency, in-vitro dissolution testing is critical for suspension of Dexamethasone, as it characterizes drug release, supports formulation optimization, and provides evidence for regulatory bio-waivers. This investigation was carried out to develop and validate a USP Type-IV flow-through cell method (closed-loop configuration) for assessing the in-vitro release behavior of dexamethasone (0.1%) from povidone-iodine (0.6%) and dexamethasone (0.1%) ophthalmic suspension. The current dissolution method employed phosphate buffer (pH 7.4) with 0.1% β-cyclodextrin as medium, chosen for solubility, stability, and sink condition. A 100 kDa cellulose ester membrane enabled controlled diffusion. Chromatographic separation was performed on an ACE Excel-5 C8 column (250 × 4.6 mm, 5 µm) using an isocratic mobile phase of 0.6% β-cyclodextrin in water and acetonitrile (1:1 v/v). Partial validation per ICH Q2(R2) confirmed excellent linearity (r² &gt; 0.999), precision (%RSD &lt; 2.0), accuracy (98.5–101.5%), and solution stability for 72 h. The method was discriminatory for formulation changes and suitable for routine and stability testing of ophthalmic suspensions.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 3","pages":"Article 104165"},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994529","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":"Development of a mechanistic in vitro-in vivo correlation for upadacitinib using physiologically-based pharmacokinetic modeling","authors":"Md Mahbubul Huq Riad ,&nbsp;Sumit Bhatnagar ,&nbsp;Susan George ,&nbsp;Patrick Marroum","doi":"10.1016/j.xphs.2026.104185","DOIUrl":"10.1016/j.xphs.2026.104185","url":null,"abstract":"<div><div>A physiologically-based pharmacokinetic (PBPK) model was successfully developed to describe the absorption, distribution, metabolism, and excretion processes for the upadacitinib 15 mg, 30 mg, and 45 mg extended-release (ER) formulations. A prior numerical in vitro-in vivo correlation (IVIVC) was established for the 15 mg and 30 mg ER formulations. A novel dissolution method had to be developed to achieve adequate in vitro upadacitinib release from the 45 mg ER formulation. A PBPK model was developed and an IVIVC using the 15 mg, 30 mg, and 45 mg ER formulations was incorporated to establish a mechanistic IVIVC framework. Importantly, the more comprehensive mechanistic IVIVC model demonstrated robustness through both internal and external validation and was able to accurately predict in vivo upadacitinib exposures in a distinct clinical trial data set using the 45 mg ER tablet in vitro dissolution data. Further, the model was able to discriminate between 15 mg, 30 mg, and 45 mg exposures. As outlined and encouraged by regulatory guidances, this validated Level A mechanistic IVIVC can serve as a surrogate for bioavailability testing, be a screening tool for future upadacitinib formulation dissolution, and set clinically relevant dissolution acceptance criteria.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 3","pages":"Article 104185"},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100374","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":"Generalized flow imaging microscopy instrument settings for measuring subvisible particle sizes and concentrations in protein therapies","authors":"Austin L. Daniels ,&nbsp;Sushma Parab ,&nbsp;Sigrid C. Kuebler ,&nbsp;Soumen Das","doi":"10.1016/j.xphs.2026.104171","DOIUrl":"10.1016/j.xphs.2026.104171","url":null,"abstract":"<div><div>Flow imaging microscopy (FIM) is a common imaging-based technique for measuring the subvisible particle content of protein therapies. FIM measurement accuracy strongly depends on particle segmentation, the process of detecting particles in digital images. Some FIM instruments like FlowCam allow users to adjust capture settings, parameters that influence segmentation algorithm performance. However, it has been challenging to identify settings that simultaneously yield accurate measurements of the various particle types found in protein formulations and common particle standards used for instrument qualification and validation. The present study describes generalized capture settings that allow FIM instruments to accurately measure the size and concentration of common particle types encountered in protein therapy development and manufacturing. The settings were developed using a mixture of qualitative and quantitative optimization strategies, as well as using both particle standards and representative samples. At these settings, FIM instruments yielded accurate measurements on opaque (e.g., polystyrene beads) and translucent (e.g., ethylene tetrafluoroethylene particles) particle standards. Protein formulations were also analyzed using these settings to investigate the impact of these settings on the measured subvisible particle content. These settings yield accurate measurements of typical particle types in protein formulations and aim to aid in standardizing FIM as an analytical technique.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 3","pages":"Article 104171"},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046617","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}