Journal of pharmaceutical sciences最新文献

{"title":"Host cell impact on pharmacokinetics and neurobiological activity of non-erythropoietic hyperglycosylated EPO variants","authors":"Francisco Iturraspe ,&nbsp;María de los Milagros Bürgi ,&nbsp;Rocío Gutiérrez Fuster ,&nbsp;Ricardo Kratje ,&nbsp;Camila Scorticati ,&nbsp;Marcos Oggero","doi":"10.1016/j.xphs.2025.103901","DOIUrl":"10.1016/j.xphs.2025.103901","url":null,"abstract":"<div><div>Human erythropoietin (EPO), which is therapeutically used to treat anemia, has demonstrated neuroprotective and neuroplastic benefits. Three glycoengineered EPO muteins designed to reduce erythropoiesis while retaining neurobiological effects were expressed in CHO.K1 and HEK-293 cells and compared both physicochemically and biologically.</div><div>Our findings demonstrated that two of the muteins preserved their tertiary structure integrity. Both HEK-293 variants exhibited lower molecular masses and fewer acidic isoforms compared to their CHO.K1 counterparts, due to their simpler glycan structures and lower sialic acid content. Disparity in the glycan profile impacted pharmacokinetics, causing HEK-derived muteins to have shorter half-lives and higher clearance rates than CHO-derived molecules.</div><div>Regardless of the host cells, all variants enhanced neuritogenesis, filopodia formation, and synaptogenesis in cultured neurons. <em>In vivo</em> analyses assessing pharmacokinetics and the complexity of dendritic arbor revealed that HEK cell-derived variants possess dendritic growth comparable to that from CHO cells (42 %-increase in dendrite length and a 41 %-increase in the number of intersections per neuron), even though the former exhibited less favorable pharmacokinetic profiles.</div><div>Since the improved pharmacokinetic properties of CHO.K1-derived EPO-based neurotherapeutics did not translate into enhanced <em>in vivo</em> hippocampal neuron arborization, HEK-293 cells represent a compelling alternative production platform, offering a more favorable glycosylation profile with simpler and less immunogenic glycans.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 9","pages":"Article 103901"},"PeriodicalIF":3.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144605659","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":"Impact of drug-polymer complexation and media properties on the release performance of amorphous solid dispersions containing a weakly basic drug and hydroxypropyl methylcellulose acetate succinate.","authors":"Amanpreet Kaur, Dmitry Zemlyanov, Lynne S Taylor","doi":"10.1016/j.xphs.2025.103894","DOIUrl":"10.1016/j.xphs.2025.103894","url":null,"abstract":"<p><p>Herein, the release performance of amorphous solid dispersions (ASDs) of a weakly basic drug, bedaquiline (BDQ), and a weakly acidic polymer, hydroxypropyl methylcellulose acetate succinate (HPMCAS) was investigated in different media. In conjunction, the complexation tendency between BDQ and HPMCAS was also probed. Amorphous solid dispersions (ASDs) of BDQ were prepared at different drug loadings with LF and MF grades of HPMCAS using solvent evaporation. Drug-polymer complexation was investigated in buffers varying in pH from 5.8 to 10.5 and in biorelevant media. For these experiments, polymer concentration was quantified using colorimetry or high-performance liquid chromatography (HPLC) and evaporative light scattering detection (ELSD). The insoluble drug-polymer complex formed in some media was analyzed using attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy. Drug release from ASD powders was evaluated as a function of pH (1.6, 3.0, 5.0, 6.5) as well as in fasted and fed state simulated intestinal fluids. HPMCAS showed a high degree of insoluble complex formation (∼90 %) with BDQ at pH 6.0 and the extent of complexation decreased with increasing pH, or when biorelevant media was used. At pH 6.5, ASDs showed a low extent of release in buffer. Release of drug from the ASDs was considerably enhanced in biorelevant media. BDQ remained amorphous in the presence of HPMCAS for extended time periods, hence crystallization was not considered a failure mechanism. Instead, the low release extent observed in pH 6.5 buffer was attributed to the formation of an insoluble BDQ:polymer ionic complex in the ASD particle. Ionic complexation was confirmed using X-ray photoelectron spectroscopy. However, it appears that solubilizing species present in the biorelevant media disrupted the drug-polymer complexation leading to improved release. These studies highlight the convoluted nature of drug release from ASDs with enteric polymers and the need to consider the impact of the release testing conditions. Release as a function of media conditions, is in turn expected to be highly variable from drug to drug depending on the nature of the drug-polymer interactions.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"103894"},"PeriodicalIF":3.7,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591511","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":"Physicochemical compatibility investigation of ciprofol injection with eight cardiovascular drugs during simulated Y-site administration","authors":"Baoxia Fang ,&nbsp;Wenya Deng ,&nbsp;Qipeng Liu ,&nbsp;Peng Chen ,&nbsp;Jing Wu ,&nbsp;Fuchao Chen","doi":"10.1016/j.xphs.2025.103897","DOIUrl":"10.1016/j.xphs.2025.103897","url":null,"abstract":"<div><div>The intravenous pharmacotherapy in patients with critically ill and perioperative intravenous anesthesia is extremely challenging due to the large number of drugs administered. In-line incompatibility remains a significant safety concern. We therefore evaluated the physico- chemical compatibility of combinations of ciprofol injection with cardiovascular drugs during simulated Y-site administration frequently used in intensive care unit setting or intravenous anesthesia. Ciprofol injection was mixed with clinical concentrations of dopamine, sodium nitroprusside, dobutamine, phentolamine, papaverine, nitroglycerin, metaraminol and methoxamine solution at a 1:1 vol ratio under ambient conditions (25 ± 1 °C). Physicochemical compatibility changes in appearance, pH values, Zeta potential, particle size/polydispersity index (PDI), osmotic pressure, and relative percentage content are observed at predetermined time points (0, 2, 4, 6, and 8 h). During the 8-hour study period, the pH values change of all drug mixture remained within ±0.4. The relative drug concentration was maintained between 95 % and 105 %. The mean particle size was in the range of 200 to 220 nm, with a PDI below 0.2. Osmotic pressure changes were consistently &lt;6 %. Notably, the Zeta potential of the metaraminol-ciprofol mixture exhibited a variation exceeding ±10 mV. Microscopic imaging analysis showed that the droplet sizes of dopamine-ciprofol, metaraminol-ciprofol, and papaverine-ciprofol mixtures, increased significantly. Based on this studies, ciprofol injection demonstrated compatibility and stability when administered via Y-site infusion with sodium nitroprusside, dobutamine, methoxamine, phentolamine, and nitroglycerin for up to 8 h at room temperature. However, the combination of ciprofol with dopamine, metaraminol, or papaverine was incompatibility during infusion. pH is a significant factor that could potentially influence the stability and compatibility of the combinations. Clinical strategies such as the use of inline filters and post-infusion irrigation tubes can prevent these risks.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 9","pages":"Article 103897"},"PeriodicalIF":3.7,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567581","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":"Fabrication and optimization of valsartan-loaded transbilosomes for management of diabetes mellitus-accelerated stroke","authors":"Amr Gamal Fouad ,&nbsp;Amany Belal ,&nbsp;Mohamed A.M. Ali ,&nbsp;Nisreen Khalid Aref Albezrah ,&nbsp;Mohammed S Alharthi ,&nbsp;Fatma I. Abo El-Ela","doi":"10.1016/j.xphs.2025.103896","DOIUrl":"10.1016/j.xphs.2025.103896","url":null,"abstract":"<div><div>Stroke is the second leading cause of death, particularly among diabetic patients. Valsartan (VST) has the potential to alleviate and prevent strokes due to its antioxidant properties. However, the poor solubility and low bioavailability of VST limit its effectiveness. Therefore, this study aimed to develop a nasal formulation of VST-loaded transbilosomes (VLT) to enhance VST’s efficacy, sustainability, bioavailability, and targeting as a treatment for diabetes mellitus-accelerated stroke (DMAS). The Box-Behnken design was employed for the formulation development and optimization of VLT. An experimental rat model of DMAS was utilized for the <em>in vivo</em> study. The optimal VLT formulation consisted of phospholipid (262.14 mg), Span 60 (20 mg), and sodium deoxycholate (10 mg). When compared to free VST, the optimal VLT formulation improved sustainability, permeability, bioavailability, and targeting of VST by 68.69 %, 7.17-fold, 6.15-fold, and 3.98-fold, respectively. Compared with the positive DMAS control, the optimal VLT group enhanced the neurobehavioral activity of DMAS rats in terms of flexion, spontaneous motor activity, time spent in the target quadrant, and grip strength by 68.52 %, 51.96 %, 83.64 %, and 2.43-fold, respectively. The histopathological study confirmed these results. In conclusion, these findings suggest that the nasal VLT formulation could be a promising therapy to prevent DMAS.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 9","pages":"Article 103896"},"PeriodicalIF":3.7,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567568","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":"3D printing personalized medications in a hospital: Rapid and non-destructive dose verification of printed medicines enabled by miniaturised spectroscopy","authors":"Anna Kirstine Jørgensen ,&nbsp;Antoine Dowek ,&nbsp;Lucas Denis ,&nbsp;Jun Jie Ong ,&nbsp;Maxime Annereau ,&nbsp;André Rieutord ,&nbsp;Maryam Parhizkar ,&nbsp;Alvaro Goyanes ,&nbsp;Abdul W. Basit","doi":"10.1016/j.xphs.2025.103895","DOIUrl":"10.1016/j.xphs.2025.103895","url":null,"abstract":"<div><div>Three-dimensional printing (3DP) of pharmaceuticals is as an enabling technology for personalised medicine and is a versatile production technology for compounding automation and decentralised manufacture. However, non-destructive quality control (QC) methods are needed for the small batch medicines production. This study investigated for the first time two miniaturised and handheld near-infrared (NIR) and Raman spectrometers as QC measures for accurately quantifying tamoxifen in medicines manufactured in Gustave Roussy Cancer Campus Hospital Pharmacy during preparation for a clinical trial. A ‘hub-and-spoke’ model approach was applied with manufacture of calibration samples in a research environment (i.e. hub or control site) for spectral data acquisition in the hospital pharmacy (i.e. spoke, point-of-care or manufacturing site) for calibration and validation (hospital pharmacy produce) samples containing 30 % w/w tamoxifen citrate, utilising the same suppliers of materials for production. Both NIR and Raman devices yielded highly accurate and predictive models from spectra acquisition into the open capsule bodies and through closed capsule shells and were deemed suitable as QC methods for rapidly determining the tamoxifen content in the medicines produced via pharmaceutical 3DP in the hospital for the clinical trial. This study proved that both miniaturised analysers may be used as non-destructive QC methods for the 3DP medicines production in the hospital pharmacy, and that a ‘hub-and-spoke’ approach for development of non-destructive chemometric models may accelerate the decentralised or modular manufacturing paradigm of 3DP medications. Future application and implementation of either technology as QC measure at decentralised manufacturing facilities may come down to other factors such as connectivity to in-line, integrated systems, costs, and safety.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 9","pages":"Article 103895"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560365","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":"Defining the Therapeutic Reference Range and Optimizing a High-Dose Discontinuation Strategy for Paroxetine Based on TDM and Population Pharmacokinetics.","authors":"Wanting Huang, Xiaolin Li, Shanqing Huang, Shanshan Huang, Hui Xia, Zhihao Guo, Hui Yan, Yuqing Li, Dewei Shang","doi":"10.1016/j.xphs.2025.103893","DOIUrl":"https://doi.org/10.1016/j.xphs.2025.103893","url":null,"abstract":"<p><p>This study aimed to determine a clinically applicable therapeutic reference range for paroxetine across commonly prescribed doses. Based on therapeutic drug monitoring (TDM) data and population pharmacokinetics (PPK), we further developed a tapering strategy optimized for high-dose discontinuation. A one-compartment PPK model was established using TDM data from 360 hospitalized psychiatric patients. Daily dose and sex significantly influenced apparent clearance (CL/F), while formulation affected apparent volume of distribution (V/F). Simulations identified an effective serum concentration range of 15-125 ng/mL for males and 30-210 ng/mL for females. Given the higher concentrations associated with high doses, a more gradual tapering strategy is recommended. This study provides a practical therapeutic reference range and a discontinuation strategy specifically tailored for high-dose regimens.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"103893"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560366","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":"Editorial Advisory Board","authors":"","doi":"10.1016/S0022-3549(25)00311-9","DOIUrl":"10.1016/S0022-3549(25)00311-9","url":null,"abstract":"","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 7","pages":"Article 103858"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144548476","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":"Di-methylation of a specific arginine in AAV5 capsid proteins","authors":"Joe Levine,&nbsp;Julie Lippincott","doi":"10.1016/j.xphs.2025.103891","DOIUrl":"10.1016/j.xphs.2025.103891","url":null,"abstract":"<div><div>We have identified significant arginine di-methylation (&gt; 40 %) on a specific arginine in AAV5 capsid proteins derived from insect cell (SF9) based systems. We have examined the capsid proteins derived from the same AAV5 serotype transgene vector construct produced using a HEK293 host cell production system and observe some, but about 10 fold less relative abundance of di-methylation on the same arginine of the capsid proteins produced with that system. This suggests there may be a relative difference in one or more aspects of post-translational di-methylation proclivity for this same site on the same protein between these two expression platforms. We also examined AAV9 serotype capsid proteins from the same two AAV production systems and observe no arginine di-methylation and/or arginine mono-methylation on any of the arginines in the capsid proteins from either. This short communication outlines details of these observations and why they may be of interest from several different perspectives.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 9","pages":"Article 103891"},"PeriodicalIF":3.7,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528453","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":"Determination of free iron content in pharmaceutical products containing different iron complexes by using polarography method: “Method development and validation study”","authors":"Remziye Azra Kartop ,&nbsp;Müge Güleli ,&nbsp;Büşra Çetin Ersen ,&nbsp;Mehmet Bulut ,&nbsp;Cem Çalışkan","doi":"10.1016/j.xphs.2025.103890","DOIUrl":"10.1016/j.xphs.2025.103890","url":null,"abstract":"<div><div>Iron carbohydrate complexes such as iron gluconate, iron sucrose, ferric carboxy-maltose, iron isomaltoside, ferumoxytol, and iron dextrans, which have been used in the treatment of iron deficiency anemia for many years, release excess iron into the circulation and produce free iron, which leads to oxidative stress and tissue damage. Therefore, the determination of free iron and keeping it within acceptable limits in pharmaceutical products is vital in product quality and patient safety. For this purpose, in the presented study, an alternative methodology is discussed for the determination of free iron in various pharmaceutical iron complexes (iron(III)-sucrose, iron(III)‑hydroxy polymaltose, and iron(III)-carboxymaltose), different from the normal pulse polarography(NPP) technique reported in the United States Pharmacopoeia (USP) for iron(III)-sucrose. The critical steps such as the selection process of parameters and analytical conditions and the accuracy of the obtained results for the polarography-based analytical method optimization of different pharmaceutical forms are examined by utilizing differential pulse polarography (DPP), which has advantages such as high sensitivity, reproducibility, and detection limits in the determination of different valence ions compared to classical methods. Thus, we aim to shed light on validation processes for the direct determination of free iron in various pharmaceutical formulations, expand the existing literature on the subject, and contribute to quality control processes in the pharmaceutical industry.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 8","pages":"Article 103890"},"PeriodicalIF":3.7,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144501218","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":"Penetration depth and effective sample size characterization of UV/Vis radiation into pharmaceutical tablets.","authors":"René Brands, Lukas Fuchs, Judith M Seyffer, Naim Bajcinca, Jens Bartsch, Urs A Peuker, Volker Schmidt, Markus Thommes","doi":"10.1016/j.xphs.2025.103889","DOIUrl":"10.1016/j.xphs.2025.103889","url":null,"abstract":"<p><p>The pharmaceutical industry is moving from off-line to real-time release testing (RTRT) to enhance quality while reducing costs. UV/Vis spectroscopy has emerged as a promising tool for RTRT given its simplicity, sensitivity and cost-effectiveness. Nevertheless, the effective sample size must be characterized in relation to the penetration depth to justify its representativeness and suitability for RTRT. In this study, bilayer tablets were produced using a hydraulic tablet press. The lower layer contained titanium dioxide and microcrystalline cellulose (MCC), while the upper layer consisted of MCC, lactose or a combination with theophylline. The thickness of the upper layer was stepwise increased. Spectra from 224 to 820 nm were recorded with an orthogonally aligned UV/Vis probe. Thereby, the experimental penetration depth reached up to 0.4 mm, while the Kubelka-Munk model yielded a theoretical maximum penetration depth of 1.38 mm. Based on these values, the effective sample sizes were determined. Considering a parabolic penetration profile, the maximum volume was 2.01 mm³. The results indicated a wavelength and particle size dependency. Micro-CT analysis confirmed the even distribution of the API in the tablets proving the sufficiency of the UV/Vis sample size. Consequently, UV/Vis spectroscopy is a reliable alternative for RTRT in tableting.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"103889"},"PeriodicalIF":3.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512066","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}