Journal of pharmaceutical sciences最新文献_第9页

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 对复方聚维酮碘眼用混悬液中地塞米松溶出度分析方法开发和验证的综合讨论。

IF 3.8 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-03-01 Epub Date: 2026-01-15 DOI: 10.1016/j.xphs.2026.104165

Likhit Mandal , Dr. Praveen Kumar Vemuri

{"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 , 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 > 0.999), precision (%RSD < 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}

引用次数: 0

Development of a mechanistic in vitro-in vivo correlation for upadacitinib using physiologically-based pharmacokinetic modeling 利用基于生理的药代动力学模型建立upadacitinib的体内外相关机制。

IF 3.8 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-03-01 Epub Date: 2026-01-30 DOI: 10.1016/j.xphs.2026.104185

Md Mahbubul Huq Riad , Sumit Bhatnagar , Susan George , Patrick Marroum

{"title":"Development of a mechanistic in vitro-in vivo correlation for upadacitinib using physiologically-based pharmacokinetic modeling","authors":"Md Mahbubul Huq Riad , Sumit Bhatnagar , Susan George , 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}

引用次数: 0

Generalized flow imaging microscopy instrument settings for measuring subvisible particle sizes and concentrations in protein therapies 用于测量蛋白质治疗中不可见颗粒大小和浓度的通用流成像显微镜仪器设置。

IF 3.8 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-03-01 Epub Date: 2026-01-23 DOI: 10.1016/j.xphs.2026.104171

Austin L. Daniels , Sushma Parab , Sigrid C. Kuebler , Soumen Das

{"title":"Generalized flow imaging microscopy instrument settings for measuring subvisible particle sizes and concentrations in protein therapies","authors":"Austin L. Daniels , Sushma Parab , Sigrid C. Kuebler , 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}

引用次数: 0

Application of ion-exchange chromatographic technique using resins to prepare the salts of polar unstable prodrugs and new chemical entities (NCEs) 离子交换色谱技术在树脂制备极性不稳定前药及新化学实体（nce）盐中的应用。

IF 3.8 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-03-01 Epub Date: 2026-01-03 DOI: 10.1016/j.xphs.2026.104152

Raja K. Rit, Venkataramasubramanian V., Deepika V., Pandiyaraj B., Umesh Waman Mali, Olivier Venier, Santoshkumar N. Patil

{"title":"Application of ion-exchange chromatographic technique using resins to prepare the salts of polar unstable prodrugs and new chemical entities (NCEs)","authors":"Raja K. Rit, Venkataramasubramanian V., Deepika V., Pandiyaraj B., Umesh Waman Mali, Olivier Venier, Santoshkumar N. Patil","doi":"10.1016/j.xphs.2026.104152","DOIUrl":"10.1016/j.xphs.2026.104152","url":null,"abstract":"<div><div>Prodrugs are inactive and bio-reversible derivatives of drugs or clinical candidates. Prodrugs and New Chemical Entities (NCEs) often do not show good bioavailability primarily due to poor solubility. One of the strategies to overcome this challenge is to use their salt forms. Conventional salt preparation techniques fail when applied to polar unstable prodrugs and NCEs. Herein, we have developed a simple efficient salt preparation technique using ion exchange resin chromatography. This technique involves the exchange of cations on sulfonic acid-based resin that could be applied successfully to prepare the salts of acidic prodrugs and NCEs. In this current work, phosphate/sulfate/carboxylate-prodrugs were prepared in the form of their inorganic (e.g. Na<sup>+</sup>, K<sup>+</sup>) and organic amine (e.g. erbumine, trizma, meglumine, arginine) salts with excellent control. The resin cartridge was reused for the preparation of different salts without any significant compromise in yields. Moreover, this protocol was employed to quickly switch the counterions for the pH-sensitive prodrugs, which is very useful in pharmaceutical development. This method is cost effective, operationally simple and presents a broad substrate scope. We wish this technique would help organic and pharmaceutical chemists to prepare various salt forms of prodrugs or NCEs in an efficient and controlled manner.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 3","pages":"Article 104152"},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906246","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}

引用次数: 0

Analysis of the formation of (sub)visual particles in ready-to-administer trastuzumab infusion bags during transport from the hospital pharmacy to patients at home 曲妥珠单抗输注袋在从医院药房运送到患者家中的过程中形成（亚）视觉颗粒的分析

IF 3.8 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-03-01 Epub Date: 2026-01-14 DOI: 10.1016/j.xphs.2026.104164

Charlotte Sikking , T.Ton Dinh , Mirjam Crul , Stefan G. Romeijn , Charlotte van Kesteren , Marieke M. Beex-Oosterhuis

{"title":"Analysis of the formation of (sub)visual particles in ready-to-administer trastuzumab infusion bags during transport from the hospital pharmacy to patients at home","authors":"Charlotte Sikking , T.Ton Dinh , Mirjam Crul , Stefan G. Romeijn , Charlotte van Kesteren , Marieke M. Beex-Oosterhuis","doi":"10.1016/j.xphs.2026.104164","DOIUrl":"10.1016/j.xphs.2026.104164","url":null,"abstract":"<div><div>For biological drugs, subvisible particle formation can cause loss of efficacy of the drug or trigger immune reactions. Transport of ready-to-administer infusion bags, to enable home treatment of cancer patients, might cause particle formation. The primary aim of this observational prospective pharmaceutical study is to investigate the effect of transport by car on the formation of subvisible particles in ready-to-administer infusion bags with trastuzumab. Hereto, trastuzumab was compounded (<em>n</em> = 19 infusion bags) in the hospital pharmacy and transported by car to patients’ homes and thereafter to the laboratory for analysis. The analysis comprised visual inspection and qualitative and quantitative analyses of particle formation. The key findings revealed no significant difference in amount of particles between transported and non-transported bags based on the FlowCam, nanoparticle and HP-SEC analyses. Light obscuration revealed a statistically significant lower amount of particles ≥10 μm in non-transported samples, although absolute numbers of these particles was low. Transporting reconstituted trastuzumab infusion bags by car does not lead to a significant increase in the amount of aggregates in the infusion bags. Therefore, with regards to particle formation, home treatment of patients with trastuzumab was safe.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 3","pages":"Article 104164"},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989762","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}

引用次数: 0

Long-acting delivery of a model monoclonal antibody from ethylene vinyl acetate implants at a high loading: Drug release and protein stability 高负荷醋酸乙烯酯植入物模型单克隆抗体的长效递送：药物释放和蛋白质稳定性。

IF 3.8 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-03-01 Epub Date: 2026-01-15 DOI: 10.1016/j.xphs.2026.104167

Yu Tong Tam , Harsh Patel , Jeffrey C. Haley , Alexander Dimmling , Devin B. Tesar , Alavattam Sreedhara

{"title":"Long-acting delivery of a model monoclonal antibody from ethylene vinyl acetate implants at a high loading: Drug release and protein stability","authors":"Yu Tong Tam , Harsh Patel , Jeffrey C. Haley , Alexander Dimmling , Devin B. Tesar , Alavattam Sreedhara","doi":"10.1016/j.xphs.2026.104167","DOIUrl":"10.1016/j.xphs.2026.104167","url":null,"abstract":"<div><div>Delivering large therapeutic monoclonal antibodies (mAbs) from solid polymer matrices via hot-melt extrusion (HME) is a promising approach to achieving a prolonged release profile. However, this approach presents significant challenges due to protein instability under high temperatures and high shear forces typically involved in the extrusion process and during extended-release duration in physiological conditions. Herein, we discuss the encapsulation of a large therapeutic mAb (MW ∼150 kDa) at a high loading (≥50%) via HME and vacuum compression molding (VCM) with ethylene vinyl acetate (EVA) and its stability analysis upon release from EVA rods. Protein stability of a model mAb (mAb1) with respect to protein aggregation, structural stability, and relative binding activity was evaluated. A solid spray-dried formulation of mAb1 can maintain its protein stability against elevated temperature and repeated heating cycles during the manufacturing process with EVA. In the present work, we show that applying a second thermal step via VCM can enable a homogeneous distribution of solid spray-dried particles of mAb1 embedded within the solid EVA matrix. Additionally, our results demonstrate that implementing a membrane coating on EVA rods can yield a slow release of mAb1 from EVA rods without significantly impacting protein stability, representing a viable approach for the long-acting delivery of mAbs using EVA as a non-biodegradable polymer implant.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 3","pages":"Article 104167"},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994475","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}

引用次数: 0

Editorial Advisory Board 编辑顾问委员会

IF 3.8 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-03-01 Epub Date: 2026-02-27 DOI: 10.1016/S0022-3549(26)00053-5

引用次数: 0

Extracellular vesicles from microalgae Pavlova in non-heated condition potently enhance innate immune response as a novel cell-derived immunostimulatory adjuvant 巴甫洛娃微藻细胞外囊泡作为一种新型细胞源性免疫刺激佐剂，在非加热条件下可增强先天免疫应答。

IF 3.8 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-03-01 Epub Date: 2026-01-10 DOI: 10.1016/j.xphs.2026.104158

Masaki Morishita , Kotaro Yamada , Toshio Taira , Ken Nakahara , Tomonori Waku , Kotone Minato , Ken-ichi Ogawara

{"title":"Extracellular vesicles from microalgae Pavlova in non-heated condition potently enhance innate immune response as a novel cell-derived immunostimulatory adjuvant","authors":"Masaki Morishita , Kotaro Yamada , Toshio Taira , Ken Nakahara , Tomonori Waku , Kotone Minato , Ken-ichi Ogawara","doi":"10.1016/j.xphs.2026.104158","DOIUrl":"10.1016/j.xphs.2026.104158","url":null,"abstract":"<div><div>In vaccine therapy, there is a growing interest in novel immunostimulatory adjuvants derived from food products or dietary supplements with safe profiles. <em>Pavlova</em> is a microalga commonly used as a dietary supplement. Owing to its immune-activating potency and safety profiles, <em>Pavlova</em> offers novel possibilities as an immunostimulatory adjuvant. However, precise control of their proliferation profile and subsequent immune activation when administered to the host is difficult, limiting their practicality as adjuvants. Extracellular vesicles (EVs) are cell-derived nanoparticles containing nucleic acids and proteins. EVs exhibit biological activity without proliferating, indicating their potential in medical applications as novel cell-free materials. However, information on EVs secreted by microalgae, including <em>Pavlova</em>, is limited. In this study, we characterized the EVs from <em>Pavlova</em> as an immunostimulatory adjuvant. Heated <em>Pavlova</em>-derived EVs (hP-EVs) and non-heated <em>Pavlova</em>-derived EVs (n-hP-EVs) were purified from their culture supernatants, with heated <em>Pavlova</em> secreting larger amounts of EVs. These EVs exhibited a particle size of approximately 130–170 nm and a negatively-charged zeta potential. RAW264.7 macrophage cells more actively took up n-hP-EVs than hP-EVs via endocytosis. As an adjuvant activity, n-hP-EVs potently increased the production of the inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), which are indicators of enhanced innate immune response. Moreover, the effect of the storage temperature on the particle size of n-hP-EVs was small, maintaining their ability to activate innate immune responses. Thus, n-hP-EVs demonstrate attractive characteristics for use as novel cell-derived immunostimulatory adjuvants.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 3","pages":"Article 104158"},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959407","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}

引用次数: 0

Investigating the SNAC-to-drug ratio for the oral absorption of cyanocobalamin in rats 研究大鼠口服氰钴胺素吸收的snc -药比。

IF 3.8 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-03-01 Epub Date: 2026-01-13 DOI: 10.1016/j.xphs.2026.104163

Po-Chang Chiang , Jia Liu , Karthik Nagapudi , Jodie Pang , Emile Plise , Michael Dolton , Matthew R. Durk

{"title":"Investigating the SNAC-to-drug ratio for the oral absorption of cyanocobalamin in rats","authors":"Po-Chang Chiang , Jia Liu , Karthik Nagapudi , Jodie Pang , Emile Plise , Michael Dolton , Matthew R. Durk","doi":"10.1016/j.xphs.2026.104163","DOIUrl":"10.1016/j.xphs.2026.104163","url":null,"abstract":"<div><div>The oral route of administration continues to be the preferred and most convenient method for drug delivery among both patients and healthcare professionals. This preference is based not only on its user-friendliness but also on the practicality it provides regarding formulation flexibility and dosage adjustability. Nevertheless, the effectiveness of oral drug delivery is significantly influenced by the ADME (Absorption, Distribution, Metabolism, and Excretion) characteristics of the drug. Among these characteristics, permeability is a key factor affecting oral bioavailability, making the exploration of permeability enhancers a vital research focus to boost oral absorption. Recent investigations have highlighted sodium N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC) as a promising permeability enhancer, demonstrating its potential to increase the absorption rates of various substances. Despite its proven effectiveness, the precise mechanisms by which SNAC promotes this enhancement are not yet fully understood. Furthermore, the specific dosage of SNAC required to improve drug absorption remains unclear. This study aims to examine the dose-dependent effects of SNAC on the model compound cyanocobalamin (Vitamin B12) in rats. The in vivo findings were integrated with modeling and simulation to determine the critical concentration of SNAC and the minimum molar ratio, and the overall enhancement effect at various SNAC concentrations for cyanocobalamin needed to achieve permeation enhancement. This knowledge could assist formulators in more effectively incorporating SNAC into formulations for enhanced therapeutic outcomes.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 3","pages":"Article 104163"},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989798","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}

引用次数: 0

Ionic strength mitigates solvent/detergent–induced tertiary expansion of hemopexin 离子强度减轻溶剂/清洁剂引起的血凝素三级膨胀。

IF 3.8 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-03-01 Epub Date: 2026-01-14 DOI: 10.1016/j.xphs.2026.104166

Min-Jung Kim , Jaeeun Jung , Jieun Kang , Nohra Park , Sung Jun Lee , Geunhye Yeo , Sangho Lee

{"title":"Ionic strength mitigates solvent/detergent–induced tertiary expansion of hemopexin","authors":"Min-Jung Kim , Jaeeun Jung , Jieun Kang , Nohra Park , Sung Jun Lee , Geunhye Yeo , Sangho Lee","doi":"10.1016/j.xphs.2026.104166","DOIUrl":"10.1016/j.xphs.2026.104166","url":null,"abstract":"<div><div>Hemopexin (Hx) is a plasma glycoprotein that scavenges free heme with sub-nanomolar affinity and under development as a therapeutic. Solvent/detergent treatment (S/D) is routinely applied to plasma-derived manufacturing for viral safety and generally considered non-disruptive. However, the histidine- and aromatic residue-rich heme pocket at the inter-domain interface may render Hx susceptible to S/D. We investigated whether S/D perturbs the tertiary structure of Hx and elevated ionic strength mitigates such effects. Changes in the apparent size and activity of Hx exposed to S/D were assessed by size-exclusion HPLC (SE-HPLC) and functional assays. S/D consistently reduced activity and shifted SE-HPLC profiles toward a larger hydrodynamic size. Small-angle X-ray scattering (SAXS) revealed expansion of the molecular envelope of Hx by S/D, suggesting that the heme pocket may initiate hinge relaxation between two β-propeller domains of Hx. To mitigate such expansion by S/D, we screened a formulation range of NaCl concentration. Increasing ionic strength compacted SAXS profiles toward the native state and restored activity, consistent with pocket stabilization by charge. These findings identify Hx as an exception to typical S/D tolerance and demonstrate that modulation of ionic strength represents an effective strategy to preserve structural integrity and function while fulfilling viral safety requirements.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 3","pages":"Article 104166"},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989735","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}

引用次数: 0