Journal of pharmaceutical sciences最新文献

{"title":"Outstanding early career scientists for 2024","authors":"Kenneth L. Audus","doi":"10.1016/j.xphs.2024.11.010","DOIUrl":"10.1016/j.xphs.2024.11.010","url":null,"abstract":"","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 2","pages":"Page 641"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143430256","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":"Spray drying process challenges and considerations for inhaled biologics","authors":"Sadegh Poozesh ,&nbsp;Patrick Connaughton ,&nbsp;Scott Sides ,&nbsp;David Lechuga-Ballesteros ,&nbsp;Sajal M. Patel ,&nbsp;Prakash Manikwar","doi":"10.1016/j.xphs.2024.11.028","DOIUrl":"10.1016/j.xphs.2024.11.028","url":null,"abstract":"<div><div>Spray drying presents numerous advantages over other drying technologies, particularly for inhaled biologics because of the fine-tuned particle attributes requirements. To fully leverage these benefits, it is crucial to address several process challenges and considerations throughout the end-to-end spray-drying process, including stages prior to, during, and post- drying. This review provides a detailed overview of the challenges associated with spray-drying of biologics along with the aspects of protein degradation. Furthermore, it delineates the entire spray-drying process, comprising feed solution preparation, spray drying, and bulk powder handling, along with protein degradation mechanisms and analytical tools for protein and aerosol performance assessment. Pertaining to inhaled biologic products, this review also sheds light on major bottlenecks and potential challenges, particularly during scale-up. While some challenges are yet to be conclusively addressed, potential control and mitigation strategies from industry perspective are presented and examined. Lastly, the review briefly explores trending topics in this field that could add value to the standard spray-drying process and may be incorporated in future drying technologies.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 2","pages":"Pages 766-781"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854442","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":"Computer modeling of bevacizumab drug distribution after intravitreal injection in rabbit and human eyes","authors":"Jabia M. Chowdhury ,&nbsp;Eduardo A. Chacin Ruiz ,&nbsp;Matthew P. Ohr ,&nbsp;Katelyn E. Swindle-Reilly ,&nbsp;Ashlee N. Ford Versypt","doi":"10.1016/j.xphs.2024.12.005","DOIUrl":"10.1016/j.xphs.2024.12.005","url":null,"abstract":"<div><div>Age-related macular degeneration (AMD) is a progressive eye disease that causes loss of central vision and has no cure. Wet AMD is the late neovascular form treated with vascular endothelial growth factor (VEGF) inhibitors. VEGF is the critical driver of wet AMD. One common off-label anti-VEGF drug used in AMD treatment is bevacizumab. Experimental efforts have been made to investigate the pharmacokinetic (PK) behavior of bevacizumab in vitreous and aqueous humor. Still, the quantitative effect of elimination routes and drug concentration in the macula are not well understood. In this work, we developed two spatial models representing rabbit and human vitreous to better understand the PK behavior of bevacizumab. This study explores different cases of drug elimination and the effects of injection location on drug concentration profiles. The models are validated by comparing them with experimental data. Our results suggest that anterior elimination is dominant for bevacizumab clearance from rabbit vitreous, whereas both anterior and posterior elimination have similar importance in drug clearance from the human vitreous. Furthermore, results indicate that drug injections closer to the posterior segment of the vitreous help maintain relevant drug concentrations for longer, improving bevacizumab duration of action in the vitreous. The rabbit and human models predict bevacizumab concentration in the vitreous and fovea, enhancing knowledge and understanding of wet AMD treatment.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 2","pages":"Pages 1164-1174"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing physicochemical properties of hydrochlorothiazide with zwitterionic L-proline and 5-fluorocytosine cocrystals through mechanochemical synthesis","authors":"Pollyana Pereira Firmino ,&nbsp;Cecilia Carolina Pinheiro da Silva ,&nbsp;Paulo Nunes ,&nbsp;José Eduardo Gonçalves ,&nbsp;Fabrizia Grepioni ,&nbsp;Javier Ellena","doi":"10.1016/j.xphs.2024.12.004","DOIUrl":"10.1016/j.xphs.2024.12.004","url":null,"abstract":"<div><div>Hydrochlorothiazide (HTZ) is a thiazide-type diuretic drug approved by the FDA in 1959 for treatment of hypertension and peripheral edema and has been used since. HTZ exhibits low solubility and low permeability, leading to variable oral bioavailability and limited intestinal drug permeability. For this reason, several attempts to improve HTZ physicochemical properties have been made during the past decades. In the broad frame of molecular crystal engineering, significant efforts and promising results in the quest for more effective solid/dosage forms of HTZ, including studies on polymorphism and cocrystals, are being developed. As part of these efforts, we report here two new cocrystals of HTZ with the zwitterionic <span>l</span>-proline and the prodrug 5-Fluorocytosine. Both cocrystals show improvement in solubility and permeability, suggesting that these new solid forms could be used as new drug candidates to deliver HTZ in the antihypertensive therapy.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 2","pages":"Pages 1152-1163"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877493","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":"The vital role of biological standardization in ensuring efficacy and safety of biological products – Historical perspectives","authors":"Rajesh K. Gupta","doi":"10.1016/j.xphs.2024.12.011","DOIUrl":"10.1016/j.xphs.2024.12.011","url":null,"abstract":"<div><div>Biological Standardization has been pivotal to the success of traditional biological products, such as vaccines, antitoxins, and immune globulins, by ensuring their quality and consistency across manufacturers worldwide. The principles of biological standardization have similarly supported the development and manufacture of safe and effective modern biological products, including hormone, therapeutic protein, and monoclonal antibody products, and continue to play a vital role in advancing new cutting-edge biological products, such as tissue, cellular, and gene-therapy products. Biological standardization started with the physical standards ensuring the reliability and suitability of methods used to test biological products and science of bioassays or biological methods and related biostatistics providing a framework for evaluating biological, functional activity or potency of these products. It expanded to include written standards defining the quality requirements for manufacturing and regulation of biological standards. Due to the shift in the biologics industry from public health to commercial-driven enterprises during the past 50 years, the biological standardization program has evolved to include the product-specific reference standards and harmonization of physical standards. The global success of conventional vaccines in controlling numerous deadly infectious diseases can largely be attributed to the availability of physical and written international standards developed through a strong biological standardization program. This article explores the evolution of biological standardization for more than a century, its scientific and regulatory principles, challenges from disruption in international standardization efforts, and future perspectives for the field.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 2","pages":"Pages 690-700"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877502","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 high-throughput micro-scale workflow to quantify molecularly dissolved drug concentrations under solubilizing conditions","authors":"Florentin Lukas Holzem ,&nbsp;Rasmus Lind Mikkelsen ,&nbsp;Jeannine Petrig Schaffland ,&nbsp;Cordula Stillhart ,&nbsp;Martin Brandl ,&nbsp;Annette Bauer-Brandl","doi":"10.1016/j.xphs.2024.12.027","DOIUrl":"10.1016/j.xphs.2024.12.027","url":null,"abstract":"<div><div>Physiological and artificial solubilizing agents usually enhance apparent solubility of poorly soluble drugs, and in many cases also oral drug exposure. However, exposure may decrease in cases where micellization reduces the molecularly dissolved drug fraction, overriding the solubility advantage. While this information is critical to accurately anticipate the effect of drug micellization on oral absorption, the experimental determination of molecularly dissolved drug concentrations is complex and time consuming.</div><div>The present study aimed at developing a micro-scale <em>in vitro</em> workflow (comparative micro-scale mass transfer assay, CMMTA) to quantify molecularly dissolved (unbound) drug concentrations in the presence of solubilizing agents.</div><div>A linear correlation was determined between the cumulative passive permeation of the model drug riluzole (RLZ) and its concentration in the donor buffer solution on a 96-well microtiter sandwich plate (PermeaPlain™). Next, the drug permeation from micellar drug solutions (in fasted and fed state simulated intestinal fluids, FaSSIF and FeSSIF) was measured and the concentration of unbound drug was derived from the aforementioned correlation. The results were validated against established methods to measure free (unbound) drug concentrations, namely equilibrium dialysis and microdialysis. The concentrations of molecularly dissolved RLZ were correctly captured on one single microtiter plate.</div><div>Both, the standard curve and samples at different solubilizing conditions can be determined simultaneously within a few hours using small quantities of drug substance. Hence, the proposed CMMTA workflow represents a promising screening tool for early-stage drug development.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 2","pages":"Pages 1485-1494"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety, tolerability, pharmacokinetic, and pharmacodynamic of CZ1S injection for unilateral brachial plexus blockade in healthy Chinese adults: Double-blind, randomized, positive-controlled Phase I study","authors":"Pengfei Zhao ,&nbsp;Dongjie Feng ,&nbsp;Haiying Wang ,&nbsp;Ting Luo ,&nbsp;Dandan Yang ,&nbsp;Zourong Ruan ,&nbsp;Linqiang Zhu ,&nbsp;Min Yan ,&nbsp;Bo Jiang","doi":"10.1016/j.xphs.2025.01.008","DOIUrl":"10.1016/j.xphs.2025.01.008","url":null,"abstract":"<div><div>CZ1S injection is a novel, extended-release local anaesthetic formulation of ropivacaine, classified as a type 2.2 new drug, with potential for post-operative analgesia by subcutaneous infiltration and peripheral nerve blockade. This study aimed to validate the superior properties of CZ1S over ropivacaine hydrochloride injection and to evaluate the safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) profiles of a single dose of brachial plexus block with CZ1S in healthy Chinese adults. The tolerability and PK profile of CZ1S were investigated following a unilateral brachial plexus injection in 24 healthy adults. Safety assessments were performed throughout the study and the PD effects of CZ1S injection for unilateral brachial plexus block were also evaluated. The results showed that CZ1S was slowly absorbed after a single injection in healthy subjects, with PK parameters of ropivacaine (including C_max, AUC_t and AUC_∞) increasing with the CZ1S doses. CZ1S demonstrated a prolonged and non-constant release profile compared to a single 75 mg injection of ropivacaine hydrochloride, resulting in a smooth and sustained blood concentration. CZ1S significantly prolonged the duration of sensory and motor blockade, and further analysis revealed a correlation between PK and sensory nerve block. The PK profile of CZ1S was enhanced compared to that of ropivacaine injection, and it was deemed safe and well tolerated in healthy Chinese adults, suggesting its potential application in postoperative analgesia.</div></div><div><h3>Clinical Trial Registration</h3><div>Chinadrugtrials.org.cn: CTR20231295 (registration date: 26 April 2023)</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 2","pages":"Pages 1245-1253"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007099","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":"The role of histidine buffer in the iron-catalyzed formation of oxidizing species in pharmaceutical formulations: Mechanistic studies","authors":"Yilue Zhang,&nbsp;Yaqi Wu,&nbsp;Christian Schöneich","doi":"10.1016/j.xphs.2025.01.003","DOIUrl":"10.1016/j.xphs.2025.01.003","url":null,"abstract":"<div><div>Iron-catalyzed oxidation reactions are common degradation pathways in pharmaceutical formulations. Buffers can influence oxidation reactions promoted by iron (Fe) and hydrogen peroxide (H₂O₂). However, mechanistically, the specific role of buffers in such reactions is not well understood. Here, we investigate the formation of radical intermediates using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a probe. Interestingly, over the time course of our experiments histidine (His) is the only buffer that promotes significant radical production during Fe(III)-catalyzed decomposition of H₂O₂, in contrast to other common pharmaceutical buffers such as citrate, succinate, adipate, and 2-(N-morpholino)ethanesulfonic acid (MES). The critical role of His in these degradation reactions is attributed to its unique, higher affinity for Fe(II) as compared to Fe(III), facilitating the reduction of Fe(III) to Fe(II) and subsequent Fenton and/or Fenton-like reactions with H₂O₂.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 2","pages":"Pages 1205-1213"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007104","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":"Experimental validation of a parenteral permitted daily exposure value for cleaning-induced degradants from recombinant therapeutic proteins with in vitro immunogenicity assays","authors":"Joseph R. Cohen ,&nbsp;Marisa K. Joubert ,&nbsp;Syeda Tabassum ,&nbsp;Allyson Capili ,&nbsp;Julia Carreon ,&nbsp;Cathie Xiang ,&nbsp;Siddharth Prabhu ,&nbsp;Anthony Merlo ,&nbsp;Dan Mytych ,&nbsp;David G. Dolan ,&nbsp;Ram Kouda","doi":"10.1016/j.xphs.2024.10.041","DOIUrl":"10.1016/j.xphs.2024.10.041","url":null,"abstract":"<div><div>Multiproduct manufacturing of biotherapeutic proteins generate cleaning-induced protein degradants because of extreme pH and temperature conditions during the cleaning process. Cleaning Acceptance limits are calculated based on the maximum allowable carryover (MAC) assessment of the previously manufactured active pharmaceutical ingredient (API) – or drug product – based on the permitted daily exposure (PDE) of the previously manufactured API into the dose of subsequent product. In this study, we tested a previously determined PDE value for cleaning-induced protein degradants of 650 µg/dose. A bench-scale cleaning method was used to generate cleaning induced degradants from both a half-life extension (HLE) BiTE® molecule and a mAb product. For this investigation, degradants of HLE BiTE®-A and mAb-1 were characterized alone or after spiking of 650 µg of degradants of HLE BiTE®-A or 650 µg degradants of mAb-1, into mAb-1, respectively. These samples were characterized by endotoxin testing, size exclusion chromatography (SEC), light obscuration by HIAC, and micro-fluidic imaging (MFI). These results suggest that significant degradation of the molecule occurs because of the cleaning procedure, and it is no longer in the intact form or active state. The potential immogenic impact was assessed using a cell line assay to assess immune activation, and a human Peripheral Blood Mononuclear Cell (PBMC) assay to assess T cell activation, T cell proliferation, and cytokine release after 20 h and 7 days. Findings from the various <em>in vitro</em> cell-based immune activation assays suggest that the presence of 650 µg of carryover of degradants either alone or spiked into the same or a cross-product do not increase immunogenicity risk in cell-based assays – suggesting that the current PDE of 650 µg/dose for cleaning-induced degradant carryover does not have a risk of immunogenicity in patients.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 2","pages":"Pages 866-877"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569074","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":"In vitro analysis of XLAsp-P2 peptide loaded cellulose acetate nanofiber for wound healing","authors":"Saranya Selvaraj ,&nbsp;Monali Perera ,&nbsp;Piumika Yapa ,&nbsp;Imalka Munaweera ,&nbsp;Inoka C. Perera ,&nbsp;Tharindu Senapathi ,&nbsp;Laksiri Weerasinghe","doi":"10.1016/j.xphs.2024.10.050","DOIUrl":"10.1016/j.xphs.2024.10.050","url":null,"abstract":"<div><div>Recently, nanofiber-based wound dressings are currently a viable strategy to expedite the healing of wounds by providing a suitable microenvironment for tissue growth with active ingredients. This research study subjects the development of electrospun cellulose acetate (CA) nanofibers loaded with the XLAsp-P2, an antimicrobial peptide (AMP) that holds great potential for enhanced wound healing as a therapeutic agent. The synthesized XLAsp-P2-loaded CA nanofibers were fabricated via three loading percentages, 0.1 %, 0.2 %, and 0.3 % w/w, and characterized and evaluated their antimicrobial potential with MTT assay and Agar overlay methods as an alternative strategy. FT-IR analysis confirmed the compatibility of the peptide-loaded CA nanocomposite, showing distinct peaks corresponding to the constituent materials. Scanning electron microscopy (SEM) analysis was employed to characterize the morphology of electrospun peptide CA nanocomposites and illustrate the fiber's size at the nanoscale. The <em>in vitro</em> release study during the 24 hr, 87 % of the peptide was released which was approximately 5.2 mg; which was closer matched to the square root model of Higuchi at room temperature. MTT assay presented sensitive results towards Gram-positive bacteria compared to Gram Negative bacteria; which corresponded to the inhibition zones of the Agar overlay method proving that <em>Escherichia coli</em> (ATCC 25922) 17.66 ± 0.38 mm and <em>Pseudomonas aeruginosa</em> (ATCC 27853) 17.44 ± 0.38 mm exhibited moderate susceptibility, while <em>Staphylococcus aureus</em> (ATCC 25923)19.89 ± 0.69 mm and <em>Bacillus cereus</em> (ATCC 11778) 23.00 ± 0.33 mm showed promising responses. Collectively, The study's findings indicate that the XLAsp-P2 incorporated CA mat possesses an opportunity to function as an efficient platform for delivering therapeutic peptides.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 2","pages":"Pages 911-922"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622886","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}