Journal of pharmaceutical sciences最新文献

Analytical Control Strategy for Biologics. Part II: Roadmap for Development and Implementation. 生物制剂的分析控制策略。第二部分：开发和实现的路线图。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-05-14 DOI: 10.1016/j.xphs.2025.103834

Krishnan Sampathkumar, Brent S Kendrick, John P Gabrielson, Da Ren

{"title":"Analytical Control Strategy for Biologics. Part II: Roadmap for Development and Implementation.","authors":"Krishnan Sampathkumar, Brent S Kendrick, John P Gabrielson, Da Ren","doi":"10.1016/j.xphs.2025.103834","DOIUrl":"https://doi.org/10.1016/j.xphs.2025.103834","url":null,"abstract":"<p><p>Biologics therapeutics encompass different modalities with vastly different molecular profiles. However, there are many similarities in the integrated product control strategy development that may be applied across the different modalities, including establishing Quality Target Product Profile (QTPP), drug substance and product development, analytical method development and qualification, process performance qualification, analytical method validation and continuous process verification. Technical and regulatory requirements for biologics development are established in numerous regulatory guidance documents issued by industry experts, ICH, FDA, EMA, and other health authorities. While there is substantial published knowledge on specific studies needed for the development of a product, there is no specific guidance on establishing a comprehensive analytical control strategy as part of an integrated control strategy in alignment with the lifecycle of product development from pre-clinical through commercialization of human biotherapeutics. This commentary is part II of a two-part commentary series on analytical control strategy development and implementation. In part I, we presented the foundations of a well-developed analytical control strategy. In this part, we present a streamlined and stage-appropriate roadmap for developing and implementing the key elements of an analytical control strategy from pre-clinical to commercial launch of therapeutic biologics.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"103834"},"PeriodicalIF":3.7,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086317","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 Effect of Solvent Polarity Environment Differences in Electrolyte and non-Electrolyte Systems. 研究电解质和非电解质体系中溶剂极性环境差异的影响。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-05-14 DOI: 10.1016/j.xphs.2025.103836

Valeria Briceida Tellez Gallego, Kate Sorg, Rodolfo Pinal

引用次数: 0

Dissolvable Microneedles assisted Minimally Invasive Transcleral Delivery of Conjugated Soluplus Nanomicelles targeting Retina in the management of Retinoblastoma. 可溶解微针辅助微创经巩膜给药治疗视网膜母细胞瘤。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-05-14 DOI: 10.1016/j.xphs.2025.103835

Mudassir Ansari, Yogesh A Kulkarni, Kavita Singh

{"title":"Dissolvable Microneedles assisted Minimally Invasive Transcleral Delivery of Conjugated Soluplus Nanomicelles targeting Retina in the management of Retinoblastoma.","authors":"Mudassir Ansari, Yogesh A Kulkarni, Kavita Singh","doi":"10.1016/j.xphs.2025.103835","DOIUrl":"https://doi.org/10.1016/j.xphs.2025.103835","url":null,"abstract":"<p><p>The present study focused on delivering sorafenib-loaded conjugated soluplus nanomicelles to the back of the eye targeting retina via dissolvable microneedle-mediated transcleral delivery. The research involved fabricating dissolvable microneedles by melt casting method using a blend of PVA and PVP 90F. Optical and scanning electron microscopy confirmed that the microneedles were sharp, smooth, non-sticky, and non-brittle, exhibiting no cracks. Mechanical testing revealed a hardness cycle of 71.63 g±5.12, with successful penetration into goat sclera, as indicated by blue dots from trypan blue staining. The drug content was consistent with the incorporation amount, measured at 10.04µg±0.67. Following rapid dissolution, the nanomicelles released the complete drug load within four hours. Drug permeation across the goat scleral membrane was estimated at 3.57±0.0.09 µg/cm², with scleral deposition of 4.99±0.13 µg, indicating effective penetration. Ocular tissue distribution analysis (LC-MS/MS) revealed sorafenib concentrations of 69.37±5.19 ng/g in the retina and 4.93±0.53 ng/g in the vitreous humor, confirming successful drug transport to the posterior eye segment. The final formulation remained stable for three months and was non-irritant, establishing a minimally invasive platform technology for the management of retinoblastoma relative to invasive eye injections.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"103835"},"PeriodicalIF":3.7,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086320","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

Validating Otto: a Franz diffusion cell autosampler to automate in vitro permeation studies 验证Otto: Franz扩散池自动进样器自动化体外渗透研究。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-05-13 DOI: 10.1016/j.xphs.2025.103837

Hayley Ka Yee Chan , Liam Archbold , Wing Man Lau , Keng Wooi Ng

{"title":"Validating Otto: a Franz diffusion cell autosampler to automate in vitro permeation studies","authors":"Hayley Ka Yee Chan , Liam Archbold , Wing Man Lau , Keng Wooi Ng","doi":"10.1016/j.xphs.2025.103837","DOIUrl":"10.1016/j.xphs.2025.103837","url":null,"abstract":"<div><div>The Franz diffusion cell (FDC) is a common apparatus for evaluating in vitro drug permeation. It has traditionally necessitated manual sampling and refilling, which requires complex scheduling, and is time-consuming and labour-intensive. The aim of this study was to develop and validate a FDC autosampler, Otto, that could be retrofitted to generic FDCs to automate sampling and refilling. Methylene blue (MB) was used as a model drug to assess the volume consistency and accuracy of the samples. Otto achieved highly consistent sample volumes (coefficient of variation, CV = 3.2 %), surpassing the consistency of manual operation (CV = 7.4 %). The amount of MB measured across multiple sampling-refill cycles mirrored the theoretical amount, as well as the amount determined through manual operation. Otto collected up to 100 samples unattended, over 24 h, in an in vitro ibuprofen permeation study. The samples were collected into standard sample vials to integrate seamlessly with downstream analytical equipment. Otto improved the quality of the permeation data over manual sampling, by sampling automatically around the clock to effectively maintain sink condition in the FDC. It therefore offers a cost-effective, performant and reliable automation solution for permeation studies that use the FDC.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 7","pages":"Article 103837"},"PeriodicalIF":3.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078491","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

Investigation of ex vivo vaginal tissue deposition and antimicrobial screening- a proof-of-concept study with doxycycline-infused in situ sol-gel for localised gonorrhoea management. 体外阴道组织沉积和抗菌筛选的研究——强力霉素注入原位溶胶-凝胶治疗局部淋病的概念验证研究。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-05-13 DOI: 10.1016/j.xphs.2025.103833

Ritu Thapa, Preeti Pandey, Marie-Odile Parat, Shila Gurung, Ella Trembizki, Taylah Anderson, David Whiley, Harendra S Parekh

{"title":"Investigation of ex vivo vaginal tissue deposition and antimicrobial screening- a proof-of-concept study with doxycycline-infused in situ sol-gel for localised gonorrhoea management.","authors":"Ritu Thapa, Preeti Pandey, Marie-Odile Parat, Shila Gurung, Ella Trembizki, Taylah Anderson, David Whiley, Harendra S Parekh","doi":"10.1016/j.xphs.2025.103833","DOIUrl":"https://doi.org/10.1016/j.xphs.2025.103833","url":null,"abstract":"<p><p>Antimicrobial resistance (AMR) associated with the leading sexually transmitted infections (STIs) such as gonorrhoea, chlamydia, and trichomoniasis has resulted in significant challenges in the prevention/treatment of these infections using current approaches. To address this, the intravaginal sol-gel platform holds immense potential, as the female reproductive tract (FRT) is the primary site of invasion and colonisation of STI-causing organisms, herein, Neisseria gonorrhoeae. The lead sol-gels, F5 and F9 demonstrate relatively low doxycycline hyclate (DOXH) tissue permeability (10.18 ± 1.56 % and 4.49 ± 1.53 %, respectively), while displaying substantive tissue deposition (2372.95 ±135.79 µg/g and 2187.73 ± 95.29 µg/g respectively) at 8 h in ex vivo bovine vaginal mucosal tissue. Furthermore, the attenuation of the deleterious effect of DOXH by the sol-gel platform on HeLa cell viability presents it as a safe drug delivery vehicle. The distinct possibility of dose reduction is demonstrated by the negligible differences in the zone of inhibition (ZoI) for sensitive isolates of N. gonorrhoeae with half-strength (0.25% w/w) and full-strength (0.5% w/w) DOXH sol-gels. In summary, intravaginal delivery using engineered DOXH-infused sol-gels presents a demonstrable solution to STI prevention/treatment with the potential to reduce AMR risk through localised drug delivery, dose reduction, and increased patient compliance.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"103833"},"PeriodicalIF":3.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078216","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

Chronopharmacokinetic model analysis of 5-fluorouracil following S-1 administration in rats: comparison with infusion and other prodrugs for chronochemotherapy S-1给药后大鼠5-氟尿嘧啶的时间代谢动力学模型分析：与输注及其他前药慢性化疗的比较。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-05-12 DOI: 10.1016/j.xphs.2025.103828

Shinji Kobuchi, Tomoki Satake, Yukako Ito

{"title":"Chronopharmacokinetic model analysis of 5-fluorouracil following S-1 administration in rats: comparison with infusion and other prodrugs for chronochemotherapy","authors":"Shinji Kobuchi, Tomoki Satake, Yukako Ito","doi":"10.1016/j.xphs.2025.103828","DOIUrl":"10.1016/j.xphs.2025.103828","url":null,"abstract":"<div><div>Circadian rhythms influence the pharmacokinetics of chemotherapeutic agents, including 5-fluorouracil, a cornerstone drug for colorectal cancer treatment. While chronomodulated chemotherapy for 5-fluorouracil infusion regimens can improve patient outcomes, the impact of circadian rhythms on oral 5-fluorouracil prodrug regimens remains poorly understood, and no dose-timing strategies have been established. This study investigated circadian variations in the pharmacokinetics of 5-fluorouracil after administering S-1, an oral fluoropyrimidine-based anticancer drug, in rats using a cosinor-based chronopharmacokinetic model. Plasma tegafur exposure showed significant circadian variation, peaking at 01:00 (17 h after light onset), whereas plasma 5-fluorouracil exposure exhibited no significant time-of-dosing differences. Chronopharmacokinetic analysis revealed minimal circadian variation in 5-fluorouracil clearance with S-1 (amplitude-to-mesor ratio: ±14.6 %) compared to long-term 5-fluorouracil infusion (±28.0 %) and other oral prodrugs including capecitabine (±43.0 %) and uracil-tegafur (±36.7 %), which showed pronounced fluctuations. These results suggest that S-1 provides consistent 5-fluorouracil exposure regardless of dosing time, offering a practical advantage by simplifying treatment schedules and reducing the need for chronomodulated therapy. This study could advance the development of 5-fluorouracil-based chronochemotherapy using oral prodrug regimens, enabling more personalized and effective cancer treatment strategies.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 7","pages":"Article 103828"},"PeriodicalIF":3.7,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078125","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

Influences of variations of the amount of compressed material on compressibility, tabletability and compactability 压缩量的变化对可压缩性、压实性和压实性的影响。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-05-10 DOI: 10.1016/j.xphs.2025.103831

Anh Tuan Tran, Stefan Klinken-Uth

{"title":"Influences of variations of the amount of compressed material on compressibility, tabletability and compactability","authors":"Anh Tuan Tran, Stefan Klinken-Uth","doi":"10.1016/j.xphs.2025.103831","DOIUrl":"10.1016/j.xphs.2025.103831","url":null,"abstract":"<div><div>Compression analysis is essential for the investigation of materials and processes in the manufacturing of pharmaceutical tablets. In the past, the influence of various process parameters on compression analysis has been investigated. The strength of these influences can significantly depend on the properties of the compressed material. One example is the effect of tablet compression speed on tabletability. The impact of tablet geometry has also been studied. However, what is still missing in the literature is the investigation of the influence of the quantity of the compressed material. This publication provides a starting point for understanding the effect of material quantity in compression analysis. In addition to the material quantity, two different tablet diameters were also investigated. The study demonstrates that the extent to which material quantity has an influence on compression analysis highly depends on the material properties. It clearly shows that the tabletability and even the compactability of materials can vary significantly depending on the amount of material compressed.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 7","pages":"Article 103831"},"PeriodicalIF":3.7,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018748","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

Analytical control strategy for biologics. Part I: Foundations 生物制剂的分析控制策略。第一部分：基础。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-05-10 DOI: 10.1016/j.xphs.2025.103826

Brent S. Kendrick , Krishnan Sampathkumar , John P. Gabrielson , Da Ren

{"title":"Analytical control strategy for biologics. Part I: Foundations","authors":"Brent S. Kendrick , Krishnan Sampathkumar , John P. Gabrielson , Da Ren","doi":"10.1016/j.xphs.2025.103826","DOIUrl":"10.1016/j.xphs.2025.103826","url":null,"abstract":"<div><div>Biologic therapeutics encompass different modalities with vastly different molecular profiles. Despite these differences, all products follow a similar approach to Pharmaceutical Development, which includes an integrated control strategy that relies on a clinical target product profile (TPP), a quality target product profile (QTPP), biophysical, biochemical and biological characterization, elucidation of critical quality attributes (CQAs), and development of an analytical control strategy. Technical and regulatory requirements for biologics development are established in numerous regulatory guidance documents issued by ICH, FDA, EMA, and other bodies. While there is substantial published knowledge on specific studies needed for development of a product, there is no specific guidance on establishing a comprehensive analytical control strategy as part of a modern integrated control strategy. This commentary is Part I of a two-part commentary series on analytical control strategy. In this part we present the foundations that are essential for developing an analytical control strategy to enable efficient lifecycle management across different biologic protein-based therapeutic modalities. In Part II, we will present a stage-appropriate roadmap to implementing an analytical control strategy from discovery research through the commercial life of the biologic.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 7","pages":"Article 103826"},"PeriodicalIF":3.7,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023233","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

High-amylose starch forms complexes with bioactive compounds present in the Amphipterygium adstringent ethanol extract. 高直链淀粉形成复合物与生物活性化合物存在于翼翼状胬肉乙醇提取物。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-05-10 DOI: 10.1016/j.xphs.2025.103824

Luis A Bello-Perez, Edith Agama-Acevedo, Josue Moreno-Zaragoza, Perla Osorio-Diaz, Daniel Arrieta-Baez

引用次数: 0

Exploring the impact of formulation and tablet shape on tablet integrity: A comprehensive investigation using mechanical and imaging techniques 探讨处方和片剂形状对片剂完整性的影响：采用机械和成像技术的综合研究。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-05-10 DOI: 10.1016/j.xphs.2025.103832

Mayank Singhal , Joona Sorjonen , Håkan Wikström , Pratik Upadhyay , Farhan Alhusban , Dean Murphy , Luis Martin de Juan , Jarkko Ketolainen , Pirjo Tajarobi

{"title":"Exploring the impact of formulation and tablet shape on tablet integrity: A comprehensive investigation using mechanical and imaging techniques","authors":"Mayank Singhal , Joona Sorjonen , Håkan Wikström , Pratik Upadhyay , Farhan Alhusban , Dean Murphy , Luis Martin de Juan , Jarkko Ketolainen , Pirjo Tajarobi","doi":"10.1016/j.xphs.2025.103832","DOIUrl":"10.1016/j.xphs.2025.103832","url":null,"abstract":"<div><div>Tablets are subjected to collisions during processing and handling which can result in defects and even failed batches at commercial scale. This study investigated the influence of composition and tablet shape on the tablet integrity under simulated stressed settings. Tablet formulations with two filler combinations were compressed to different shapes and tensile strengths. Tablet integrity was characterized using tensile strength, friability, drop test, impact testing, indentation and X-ray microtomography. Pharmacopeial tests demonstrated that all tablets including the lowest tensile strength tablets had acceptable integrity. Impact testing and drop test provided stressed conditions to discriminate and rank the tablet integrity according to the composition and shape. Microtomography and indentation results revealed heterogenous density distribution with respect to tablet shape and the composition. Increasing the amount of microcrystalline cellulose was the most successful approach to address tablet integrity issues. Tablet shape also influenced the number as well as the nature of tablet defects. Application of more discriminating tests could serve as extra tools to support selection of right tablet shape and composition. This can lead to the development of a robust formulation with potential to save resource required for troubleshooting tablet defect during both clinical and commercial supply.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 7","pages":"Article 103832"},"PeriodicalIF":3.7,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022897","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