Journal of pharmaceutical sciences最新文献

{"title":"Effectiveness of manufacturing annealing temperature on sterilization and depyrogenation of closed ampoules compared with other techniques","authors":"Ahmed M. Rashed ,&nbsp;Ahmed M.A. Hetta ,&nbsp;Zeinab S. Hashem ,&nbsp;Mo'men H. El-Katatny","doi":"10.1016/j.xphs.2025.103769","DOIUrl":"10.1016/j.xphs.2025.103769","url":null,"abstract":"<div><div>The presence of endotoxin in the bloodstream can lead to unexpected fever and, in severe cases, endotoxemia and bacteremia that can lead to death. The reduction of bacterial endotoxin, known as depyrogenation, is crucial for preparing primary packaging components like ampoules for use in injectable drug products. The durability of glass ampoules depends on the proper annealing process. If glass is not annealed correctly, it is prone to cracking or shattering from even small changes in temperature or from mechanical shock or stress. To evaluate the effectiveness of sterilization and depyrogenation, a dry heat oven at 250°C was used for 30 min. The Limulus Amebocyte Lysate (LAL) assay was utilized to detect endotoxin, and efficient sterilization and depyrogenation were observed at this temperature. The impact of heating glass ampoules to various temperatures on the process of sterilization and depyrogenation was studied. This investigation covered a range of temperatures (250°C - 550°C), and included holding stage times (105, 120, and 200 s) corresponding to the belt speed. The removal of endotoxins was achieved by exposing to temperatures from 350°C to 550°C for specific time intervals and at 300°C with an exposure time of 200 s. The absence of endotoxin was observed when annealing glass ampoules at 500°C for 105 s, regardless of the ampoules' size. Alternative methods for testing depyrogenation of sealed ampoules, such as ethylene oxide (EtO), sodium hydroxide (NaOH), and hydrochloric acid (HCl), were also demonstrated to have a clear comparison against temperature which considered the best effective economic method . This research indicates that annealing sealed glass ampoules at specific temperatures can serve as a replacement for sterilization and depyrogenation processes prior to filling, leading to savings in time, labor, machine work, energy, and cost.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 6","pages":"Article 103769"},"PeriodicalIF":3.7,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692551","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":"Sequence optimization of lipid-modified amphiphilic tetrapeptides as anticancer drug carriers","authors":"Asuka Inada,&nbsp;Ayane Sawao,&nbsp;Mizuki Shinoda,&nbsp;Tatsuya Oshima","doi":"10.1016/j.xphs.2025.103768","DOIUrl":"10.1016/j.xphs.2025.103768","url":null,"abstract":"<div><div>In this study, 19 tetrapeptides, each consisting of four amino acid residues, were designed and modified with oleic acid to serve as amphiphilic dispersants for anticancer drug delivery. The lipid-modified peptides (Ole-pep) were evaluated for their ability to disperse paclitaxel (Ptx), a poorly water-soluble anticancer drug. The water dispersibility of Ptx was significantly increased when peptides with two or more positively or negatively charged functional groups were used as dispersants. One specific Ole-pep demonstrated a critical micelle concentration of 0.0682 × 10⁻³ mol/dm³, confirming its excellent amphiphilic properties and capacity to encapsulate Ptx. Cytotoxicity studies in HeLa cells, a cell line derived from human cervical cancer cells, confirmed that the complexes with Ptx were highly cytotoxic regardless of the peptide used. Additionally, the results suggested that certain peptides, particularly those with a high number of Lys residues, exhibited cytotoxicity on their own.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 6","pages":"Article 103768"},"PeriodicalIF":3.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692554","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":"Microfluidic blood-milk barrier and physiologically based pharmacokinetic model to predict lofexidine secretion into breast milk","authors":"Sanat Kumar Dash ,&nbsp;Mohammad Asikur Rahman ,&nbsp;Bofang Yi ,&nbsp;Brianna Williams ,&nbsp;Gi S. Lim ,&nbsp;Sindi Zhou ,&nbsp;Peng Zou ,&nbsp;Yanyan Li ,&nbsp;Gretchen J. Mahler ,&nbsp;Tao Zhang","doi":"10.1016/j.xphs.2025.103767","DOIUrl":"10.1016/j.xphs.2025.103767","url":null,"abstract":"<div><h3>Introduction</h3><div>Lofexidine (LUCEMYRA®) is the only FDA-approved, non-opioid, non-addictive treatment for opioid withdrawal symptoms, crucial for postpartum and pregnant women affected by the opioid crisis. Despite its clinical importance, data on its secretion into breast milk is limited. This study aims to develop a novel, microfluidic-based blood-milk-barrier on a chip model, a static human mammary cell transwell model, and a physiologically based pharmacokinetic (PBPK) lactation model to estimate the breast milk secretion of lofexidine, thereby ensuring maternal and infant safety and improving withdrawal management.</div></div><div><h3>Methods</h3><div>A novel microfluidic device was developed to build a mammary epithelium-on-a-chip model, and a transwell plate was used to develop a static mammary epithelium using a human noncarcinogenic mammary epithelial cell (MEC) population that can form an integrated barrier with tight junctions. Both models were used to evaluate the transfer of lofexidine through the in vitro mammary cell barrier. The fraction of unbound lofexidine in the breast milk was determined by a Rapid Equilibrium Dialysis (RED) assay. Eleven approaches, including a novel, previously published in vitro to in vivo extrapolation (IVIVE) approach and various other approaches, were used to estimate milk-to-plasma (M/P) ratios of lofexidine. A whole-body lactation PBPK model was built using Simcyp® simulator v22 and used to predict the concentration-time profiles of lofexidine in both human plasma and breast milk.</div></div><div><h3>Results</h3><div>A subpopulation of human normal mammary epithelial MCF10A cells (named MCF10A-TJ) was identified to form an integrated barrier that reaches trans-epithelial electrical resistance (TEER) values of over 1000 Ω·cm² by culturing with in-house designed maintenance and boosting medium. The microfluidic device-based mammary epithelium-on-a-chip model generated slightly higher lofexidine permeability values than the static transwell mammary epithelial cell model. The predicted milk-to-plasma (M/P) ratio of lofexidine ranged from 0.40 to 15.88. Four approaches estimated an M/P ratio below 1, while seven predicted values above 1, mostly between 1.35 and 5.48. The whole-body lactation PBPK model predicted the concentration-time profile of lofexidine in breast milk, with an estimated M/P ratio of approximately 2.0. This value falls within the mid-range of the predictions obtained from all eleven methods.</div></div><div><h3>Conclusion</h3><div>This study introduces comprehensive and novel approaches to predict lofexidine secretion into breast milk. Most predictions suggest higher lofexidine concentration in milk than in plasma, raising potential safety concerns for opioid withdrawal management. Further pharmacokinetic clinical lactation studies are needed to validate these predictions.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 6","pages":"Article 103767"},"PeriodicalIF":3.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670182","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":"Procedural modifications proposed for the screening of substances extracted from pharmaceutical packaging systems and medical devices with the goal of improving inter-laboratory consistency of the data generated","authors":"Steven A. Zdravkovic ,&nbsp;Samuel Kikandi ,&nbsp;Qiang Fu ,&nbsp;Bhargava Jana ,&nbsp;Jason Creasey ,&nbsp;Aaron Flick ,&nbsp;Lee Nagao ,&nbsp;Mary Kate Bielinski","doi":"10.1016/j.xphs.2025.103764","DOIUrl":"10.1016/j.xphs.2025.103764","url":null,"abstract":"<div><div>Substances that migrate (<em>leachables</em>) into a pharmaceutical product from the materials that comprise its manufacturing, packaging, and/or delivery system(s) have the potential to negatively impact its safety and/or quality. Mitigating the impact of this interaction typically includes the screening of substances that can be extracted (<em>extractables</em>) from these materials using appropriate solvents and exposure conditions. Despite the importance of such extractable screening studies in assuring product quality and patient safety, it has become apparent that inconsistencies in their execution between laboratories have resulted in the potential for differences in the qualitative and/or quantitative aspects of the extractable profiles obtained. Since this issue was discovered primarily through anecdotal accounts, a working group within ELSIE conducted two industry surveys that inquired into impactful variables of extractable screening study design and execution. After completion of these surveys, it was concluded that there were numerous variables where labs were not well aligned, which may be impacting the consistency of the data generated to some extent. To that end, this commentary summarizes recommendations proposed by the ELSIE working group to address the discrepancies in extractable study design and ultimately produce more consistent and reliable extractable profiles between laboratories.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 5","pages":"Article 103764"},"PeriodicalIF":3.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674094","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":"Thermodynamic analysis of synergistic effect of cyclodextrins and electrolytes on the solubility of aromatic amino acids.","authors":"Maame Esi Baidoo, Jonghoon Kang","doi":"10.1016/j.xphs.2025.103762","DOIUrl":"10.1016/j.xphs.2025.103762","url":null,"abstract":"","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"103762"},"PeriodicalIF":3.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670184","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":"Response with statistical assessment to \"Thermodynamic analysis of synergistic effect of cyclodextrins and electrolytes on the solubility of aromatic amino acids\".","authors":"Masakazu Fukuda, Kanako Takahashi, Toru Takarada, Shunsuke Saito, Masafumi Tanaka","doi":"10.1016/j.xphs.2025.103763","DOIUrl":"10.1016/j.xphs.2025.103763","url":null,"abstract":"","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"103763"},"PeriodicalIF":3.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670183","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)00215-1","DOIUrl":"10.1016/S0022-3549(25)00215-1","url":null,"abstract":"","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 4","pages":"Article 103757"},"PeriodicalIF":3.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642522","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":"Ternary Lipids-based Novel Thermoresponsive Lipid Nanoparticles for Targeting Doxorubicin to Breast Cancer Cells","authors":"Maryam Anwar ,&nbsp;Mubashar Rehman ,&nbsp;Tofeeq Ur-Rehman ,&nbsp;Muhammad Imran Khan ,&nbsp;Naveed Ahmed ,&nbsp;Asadullah Madni ,&nbsp;Muhammad Tayyab","doi":"10.1016/j.xphs.2025.103723","DOIUrl":"10.1016/j.xphs.2025.103723","url":null,"abstract":"<div><div>Conventional thermoresponsive liposomes have failed to meet cancer targeting potential due to poor safety profile, unpredictable fate, and low therapeutic response in clinical studies. Recently, we reported phase-change nanostructured lipid carriers, termed thermoresponsive lipid nanoparticles (TLNs), for targeting cancer cells under hyperthermia. Herein, we have prepared ternary eutectic mixtures of myristic, stearic, and palmitic acid at a ratio of 2.5:1:1.5 yielded a melting point or solid-liquid phase transition temperature of 41°C. Doxorubicin (DOX)-loaded TLNs were fabricated and optimized using Box-Behnken Design Expert® software and exhibited desirable particle size (191.7±2.88 nm), polydispersity index (0.213±0.025), zeta-potential (-21.2±2.29 mV), spherical shape, high entrapment efficiency (92.24±1.05), and desirable physicochemical stability. <em>In-vitro</em> drug release studies showed hyperthermia-aided abrupt DOX release within 2 hours at 41°C and 43°C while sustained drug release pattern for 12 hours at 37°C. <em>In-vitro</em> cytotoxicity studies of TLN also exhibited the highest breast cancer (MCF-7) cells killing at hyperthermia (41°C), more than 3-fold compared to 37°C and free DOX solution. A 23-fold higher cell uptake in breast cancer cells further confirmed that ternary eutectic mixture-based DOX-loaded TLNs are an excellent candidate for breast cancer targeting and may be preferred over other nano-carriers due to the feasible preparation and superior stability.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 6","pages":"Article 103723"},"PeriodicalIF":3.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663718","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":"Predictive dissolution modeling across USP apparatuses I, II, and III","authors":"Alexander M. Kubinski ,&nbsp;Ricardo D. Sosa ,&nbsp;Gayathri Shivkumar ,&nbsp;Reuben Georgi ,&nbsp;Susan George ,&nbsp;Eric J. Murphy ,&nbsp;Tzuchi R. Ju","doi":"10.1016/j.xphs.2025.103765","DOIUrl":"10.1016/j.xphs.2025.103765","url":null,"abstract":"<div><div>Dissolution testing provides <em>in vitro</em> drug release characterization and serves a critical role in the development of solid oral dosage forms. The most common dissolution apparatuses are the USP apparatuses I and II, for which <em>in silico</em> tools have been previously developed for predictive dissolution modeling (PDM). While apparatuses I and II serve the greater volume of projects, apparatus III offers higher agitation levels and multivessel capabilities, which is critical for certain projects, and the physics of which have not been previously characterized. To mitigate that knowledge gap, the present work characterizes the transport physics and thermodynamics of dissolution apparatus III, such that a 1-D model is established and validated which scales release kinetics with agitation level across apparatuses I, II, and III. The resulting PDM is calibrated with at least two dissolution experiments at different agitation levels, for a particular formulation-medium combination, after which release kinetics are predicted within the design spaces of the three apparatuses. Calibration data can come from experiments using a single apparatus or different apparatuses, while still predicting across all three apparatuses. Erosion-based formulations are used for validation. Additionally, apparatus III vessel residence time analysis is demonstrated.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 6","pages":"Article 103765"},"PeriodicalIF":3.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663712","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":"Streamlining viral safety in AAV manufacturing: simultaneous cell lysis and viral inactivation using biodegradable detergents","authors":"Tuhidul Islam,&nbsp;Jungmin Oh,&nbsp;Lori Fortin,&nbsp;Courtney Connors,&nbsp;Nandkumar Deorkar","doi":"10.1016/j.xphs.2025.103761","DOIUrl":"10.1016/j.xphs.2025.103761","url":null,"abstract":"<div><div>Ensuring viral safety in biopharmaceutical production is vital for global regulatory standards adherence and safeguarding patients. This study evaluates the efficacy of newly developed biodegradable detergent formulations, designed to comply with regulatory requirements, for inactivating enveloped viruses during the cell lysis step of adeno-associated virus (AAV) production. Virus clearance (VC) studies showed robust inactivation kinetics against Xenotropic Murine Leukemia Virus (XMuLV), achieving a log reduction value (LRV) of ≥5.34 within 30 to 120 min. Comparative testing in crude cell lysate and PBS buffer showed consistent viral inactivation across different matrices, highlighting the versatility of the detergent formulations. Importantly, the detergent composition preserved AAV capsid integrity, and subsequent purification steps, including affinity and ion-exchange chromatography, effectively removed residual detergent. Overall, this study demonstrates the potential of biodegradable detergents to simultaneously facilitate cell lysis and viral inactivation in AAV manufacturing, offering a sustainable alternative that aligns with industry standards.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 6","pages":"Article 103761"},"PeriodicalIF":3.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663715","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}