Journal of pharmaceutical sciences最新文献

{"title":"Design and synthesis of carbamate-linked ester prodrugs selectively activated by carboxylesterase 1 with enhanced stability against intestinal hydrolysis","authors":"Masato Takahashi,&nbsp;Shintaro Sakamoto,&nbsp;Nao Sakamoto,&nbsp;Sora Nishimura,&nbsp;Seonho Hwang,&nbsp;Jihyun Kim,&nbsp;Masakiyo Hosokawa","doi":"10.1016/j.xphs.2025.104146","DOIUrl":"10.1016/j.xphs.2025.104146","url":null,"abstract":"<div><div>Ester-based prodrugs are often prematurely hydrolyzed by intestinal carboxylesterases, leading to reduced bioavailability and potential gastrointestinal (GI) toxicity. To overcome this limitation, a series of diester, carbonate-linked ester, and carbamate-linked ester prodrugs were synthesized and evaluated using human liver microsomes (HLM), human intestinal microsomes (HIM), and recombinant carboxylesterases (CES1A1 and CES2A1). Under strongly acidic conditions (pH 1.2), all prodrugs remained highly stable (&gt;98% remaining after 6 h). In human plasma, however, diester prodrugs showed relatively rapid degradation (approximately 50% remaining after 6 h), whereas carbonate- and carbamate-linked esters displayed enhanced stability. Diester and carbonate-linked ester prodrugs were hydrolyzed by both HLM and HIM, indicating non-selective activation. By contrast, several carbamate-linked ester prodrugs showed high HLM/HIM selectivity, with CES1A1/CES2A1 hydrolysis rate ratios exceeding 50. Docking simulations showed favorable active-site binding of carbamate-linked ester prodrugs to CES1A1 but not to CES2A1, supporting the selectivity of CES1A1. These findings suggest that carbamate-based prodrug strategies can be employed to improve intestinal stability and enable controlled systemic activation, potentially reducing off-target effects and enhancing oral drug delivery. This strategy may also be applicable to liver- or lung-targeted prodrug design.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 2","pages":"Article 104146"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846798","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 multicompartment stomach physiologically-based pharmacokinetic model capturing gastric reacidification can improve food effect predictions of weak bases","authors":"Lisa Cheng ,&nbsp;Po-Chang Chiang ,&nbsp;Matthew R Wright ,&nbsp;Harvey Wong","doi":"10.1016/j.xphs.2026.104155","DOIUrl":"10.1016/j.xphs.2026.104155","url":null,"abstract":"<div><div>Various changes within the gastrointestinal tract following meal intake may significantly impact oral drug absorption. Physiologically-based pharmacokinetic (PBPK) models are often used to perform early predictions of food effects on oral absorption. However, the stomach compartment within these physiological models does not wholly reflect physiology of the fed state. The current approach where the stomach compartment is fixed at pH 5 overlooks the changing gastric pH profile over time after food consumption. We suggest the integration of a multicompartment stomach that represents the various pH phases of the fed stomach to better capture ionizable drug dissolution. Ibuprofen sodium (weak acid) and posaconazole (weak base) were investigated to determine whether a PBPK model that could better capture the varying gastric pH would yield an improvement in food effect predictions. The one-compartment and multicompartment stomach models’ simulations for ibuprofen sodium exposure with and without food consumption were comparable. For posaconazole, the one-compartment stomach model predicted a smaller area under the curve and lower maximum plasma concentration than the multicompartment stomach model’s output in the fed state. Although both models accurately predicted a positive food effect, the magnitude of the simulated fed to fasted fold-changes in posaconazole exposure by the one-compartment stomach model was much less than observed fold-changes. These results suggest that a multicompartment stomach model featuring gastric re-acidification associated with food intake should be incorporated for more accurate food effect predictions for weakly basic compounds.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 2","pages":"Article 104155"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906249","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":"Paper-based reaction devices as accelerated platforms in forced degradation studies","authors":"Airton G. Salles Jr. ,&nbsp;Willian R. de Araujo ,&nbsp;Manoel T. Rodrigues Jr. ,&nbsp;Bruno B. Guidotti","doi":"10.1016/j.xphs.2025.104111","DOIUrl":"10.1016/j.xphs.2025.104111","url":null,"abstract":"<div><div>The stability of pharmaceutical compounds is a central concern in drug development, as degradation can compromise both efficacy and safety. Conventional forced degradation studies, while effective, are often time-consuming and resource-intensive, highlighting the need for accessible and high-throughput alternatives. In this study, we introduce paper-based reaction devices (PRDs) as an innovative platform for accelerating drug degradation experiments. Strips of cellulose paper were employed as reactive microenvironments to investigate the degradation of two model drugs, cyclobenzaprine (CBP) and deflazacort (DFL), under oxidative, acidic, basic, and metal-ion stress conditions. Chromatographic analysis using HPLC-PDA and high-resolution mass spectrometry (HRMS) revealed that the paper interface preserved mechanistic relevance, yielding degradation profiles consistent with solution-based studies while markedly enhancing degradation rates. Mechanistic trends were consistent with the hypothesis that hydroxyl-rich cellulose surfaces promote kinetic amplification through hydrogen-bond-mediated microconfinement. Mass-balance assessments demonstrated reproducibility and validated the reliability of the approach across stress conditions. The PRD approach is proposed as an investigational and preformulation-level tool for early-phase stability assessment, complementing rather than replacing conventional stress testing methods. Its simple, robust, and high-throughput format offers a valuable alternative for rapid stability evaluation during the early stages of drug development and formulation design.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 2","pages":"Article 104111"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696044","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":"Lipid-free, thermostable mRNA vaccines prepared using atomic layer deposition","authors":"Holly J. Coleman ,&nbsp;Amber Rauch ,&nbsp;Erika Langsfeld ,&nbsp;Kimberly Anderson ,&nbsp;Urvi Parlikar ,&nbsp;Hans H. Funke ,&nbsp;Robert L. Garcea ,&nbsp;Theodore W. Randolph","doi":"10.1016/j.xphs.2025.104066","DOIUrl":"10.1016/j.xphs.2025.104066","url":null,"abstract":"<div><div>Lipid nanoparticle (LNP) formulations of mRNA vaccines have played a pivotal role in combatting SARS-CoV-2 infections and are expected to be a useful vaccine modality against other pathogens. However, the instability of mRNA-LNP vaccines requires their storage at temperatures below 0 °C and presents manufacturing challenges. We describe thermally stable, lipid-free mRNA vaccines prepared by spray-drying to embed mRNA within glassy polysaccharide microparticles, followed by atomic layer deposition (ALD) to encapsulate the microparticles within protective alumina shells that provide temporally controlled antigen release and facilitate cellular uptake. Using mRNAs encoding for ovalbumin, the modified HIV envelope trimer protein N332-GT2, and green fluorescent protein (GFP), we show that alumina-coated microparticles containing lipid-free mRNA are internalized by cultured macrophages <em>in vitro,</em> elicit robust immune responses compared to LNP-based mRNA vaccines <em>in vivo,</em> and are stable when stored for 6 months at temperatures up to 40 °C. Thus, alumina-coated mRNA vaccines may overcome current limitations of mRNA-LNP vaccines without using LNPs or other lipid-based carriers.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 2","pages":"Article 104066"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530726","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":"Outstanding early career scientists for 2025","authors":"Kenneth L. Audus","doi":"10.1016/j.xphs.2025.104073","DOIUrl":"10.1016/j.xphs.2025.104073","url":null,"abstract":"","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 2","pages":"Article 104073"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145574004","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":"Preparation and characterization of oral insulin-trimethyl chitosan complex-loaded solid self-nanoemulsifying drug delivery systems (SNEDDS)","authors":"Richieline S. Cual,&nbsp;Tajmarah Ayyah M. Sandato,&nbsp;Mae Quenie T. Pontanar","doi":"10.1016/j.xphs.2025.104149","DOIUrl":"10.1016/j.xphs.2025.104149","url":null,"abstract":"<div><div>Insulin, a pancreatic hormone regulating blood glucose, is available in forms of syringe, pen, or implants; however, these methods presented challenges related to skin adverse reactions and patient compliance. Oral insulin delivery has long been explored due to higher compliance and reduced costs. Similar to natural insulin secretion, but prone to GIT breakdown and low bioavailability. SNEDDS has been investigated to address these in protein formulations. This study formulated Insulin into SNEDDS with trimethyl chitosan and spray-dried for stability, then analyzed for properties and drug release. The study successfully prepared Insulin-TMC SNEDDS with a 36.17±4.02 s emulsification time, forming a Grade B nanoemulsion. Droplet sizes remained nanoscale (134.20–287.20 nm for liquid, 188.77–214.93 nm for solid), preserving characteristics post–spray drying. Stability was confirmed in TMC-free formulations, while TMC variants showed sedimentation over time. TMC-containing Solid-SNEDDS showed moisture content below 5 %, indicating good stability. Insulin release varied with pH—highest at pH 2.5 with 3 mg/mL TMC (105.48 % cumulative percent drug release), while lower releases were seen at pH 6.6 (61.73±1.38 %) and 7.0 (61.73±1.38 %) without TMC. The study supports TMC-based SNEDDS and spray drying as a potential method for oral insulin delivery.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 2","pages":"Article 104149"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889374","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":"Continuous lyophilization of suspended vials with per-vial inline analytics","authors":"Bernhardt L. Trout ,&nbsp;Steven J. Burcat ,&nbsp;Rohan P. Kadambi ,&nbsp;Lorenzo J. Stratta ,&nbsp;Richard D. Braatz ,&nbsp;Roberto Pisano ,&nbsp;Alexander H. Slocum","doi":"10.1016/j.xphs.2026.104157","DOIUrl":"10.1016/j.xphs.2026.104157","url":null,"abstract":"<div><div>Pharmaceutical lyophilization (vacuum freeze-drying) removes water from aqueous drug products to stabilize formulations. This work presents a continuous final-dose pharmaceutical lyophilizer that can integrate with continuous production chains, increasing process quality, speed, and flexibility. Performance is assessed by freeze-drying various model formulations, and the cakes produced showed no visual defects, low residual moisture, and no loss in bioactivity. Moreover, this system moves vials via magnetic levitation and includes process analytical technologies (PAT) to monitor the sublimation rate and temperature of every vial in the system, enabling the possibility of real time release and model-based feedback control to optimize drying conditions. The modular design of this continuous lyophilizer provides a direct link between laboratory and production-scale equipment, greatly simplifying the scale-up difficulty found in the traditional batch process.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 2","pages":"Article 104157"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959439","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":"When heat strikes: Investigating unexpected particles in sodium bicarbonate injections","authors":"Narasimha Swamy Kollu,&nbsp;Ravikiran Allada","doi":"10.1016/j.xphs.2025.104127","DOIUrl":"10.1016/j.xphs.2025.104127","url":null,"abstract":"<div><div>The presence of particles in injectable formulations presents significant risks, such as embolism, phlebitis, and thrombophlebitis. Moreover, visible particles violate pharmacopeial standards and may lead to regulatory actions. Therefore, it is crucial to identify the underlying cause and eliminate visible particles to ensure both patient safety and regulatory compliance. Sodium Bicarbonate Injection, a straightforward formulation containing only the active pharmaceutical ingredient and water for injection, is commonly packaged in glass vials for commercial use. This study reports an unexpected observation that, when subjected to sterilization at 121 °C, Sodium Bicarbonate Injection can develop particulate matter. Through thorough analysis, we discovered that the particles as crystals of sodium dawsonite; surprisingly, this forms at high temperatures due to the interaction between the drug product and aluminium leached from the glass vial. This important finding highlights the risks associated with exposing the drug product to elevated sterilization temperatures, emphasizing the need for alternative sterilization methods or careful optimization of heat-based conditions. It also underscores the importance of particle identification through the use of a combination of techniques that help identify the root cause and prevent formation, thereby ensuring safety and efficacy.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 2","pages":"Article 104127"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751982","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":"Investigation on the contribution of self-assembled bile salt micelles in the intestinal tract to the synergistic absorption of medicine","authors":"Ting Le ,&nbsp;Su Wang ,&nbsp;Mian Zhao ,&nbsp;Wenliang Kuang ,&nbsp;Changshun Chen ,&nbsp;Zhiwei Zhou ,&nbsp;Zhe Li ,&nbsp;Songhong Yang ,&nbsp;Wenting Wu","doi":"10.1016/j.xphs.2025.104062","DOIUrl":"10.1016/j.xphs.2025.104062","url":null,"abstract":"<div><div>Bile salt vesicles (BSVs) are phases formed by the self-assembly of bile salts and phospholipids in the intestinal endogenous environment, which play a crucial role in the absorption of insoluble components. Reciprocal absorption of drug pairs is considered to be one of the potentiating mechanisms of herbal medicine compounding; however, the contribution of intestinal BSVs in the reciprocal absorption of drug pairs needs to be explored. In this study, <em>Pueraria lobata</em>-<em>Salvia miltiorrhiza</em> was used as a model drug pair. Puerarin (PUE), the main constituent of <em>Pueraria lobata</em>, and the predominant fat-soluble constituents of Tanshinone IIA (TSA) and Cryptotanshinone (CTS) and water-soluble constituents Danshensu (DSS) of <em>Salvia miltiorrhiza</em> were selected as model drugs. Blank BSVs, three co-loaded BSVs fabricated from Sodium Taurocholate and Egg Yolk Lecithin (TL/BSVs), and four mono-loaded TL/BSVs were subsequently prepared by the film hydration method. The co-loaded TL/BSVs prepared were BSVs for co-delivery of PUA and TSA (PT-TL/BSVs), BSVs for co-delivery of PUA and CTS (PC-TL/BSVs), BSVs for co-delivery of PUA and DSS (PD-TL/BSVs), prepared single drug-loaded TL/BSVs were BSVs for co-delivery of PUA and TSA (PT-TL/BSVs), BSVs for co-delivery of PUA and CTS (PC-TL/BSVs), BSVs for co-delivery of PUA and DSS (PD-TL/BSVs), and they were evaluated in vitro and in vivo. The effects of different drug-loaded TL/BSVs prepared in vitro and self-assembled TL/BSVs in the intestinal environment on the absorption of the \"<em>Pueraria lobata</em>-<em>Salvia miltiorrhiza</em>\" drug pairing were investigated by comparing the absorption of three combinations of PUA-TSA, PUA-CTS, and PUA-DSS in the bile and bile-less models. The endogenous BSVs were approved to have positive effect on the intestinal absorption of the \"<em>Pueraria lobata</em>-<em>Salvia miltiorrhiza</em>\" medicine pair, due to their solubilization effect on PUA, TSA, CTS, DSS. Moreover, compared with mono-loaded BSVs, the better structural stability of co-loaded BSVs was observed, which is beneficial to the BSVs’intestinal transportation and the absorption of the active compounds of <em>Pueraria lobata</em>-<em>Salvia miltiorrhiza</em>. Accordingly, this work demonstrates that the BSVs plays an important role in the reciprocal absorption of drug pairs, which provides a new research perspective for elucidating the modern scientific connotation of drug pair compatibility.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 2","pages":"Article 104062"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145523695","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":"Chemical instability of cefaclor in simple suspensions alkalinized with magnesium oxide and the structural elucidation of the degradation products","authors":"Ginjiro Kato ,&nbsp;Hidemichi Mitome ,&nbsp;Mitsuki Yamanaka ,&nbsp;Noriaki Hidaka ,&nbsp;Mamoru Tanaka ,&nbsp;Kazuki Akira","doi":"10.1016/j.xphs.2025.104063","DOIUrl":"10.1016/j.xphs.2025.104063","url":null,"abstract":"<div><div>A simple suspension method, where solid formulations are soaked in water (55 °C) and suspended followed by tube administration, has been widely used in Japan for patients with dysphagia. However, information on the chemical stability of drugs concomitantly suspended with acidic or basic ones is insufficient. Cefaclor, a β-lactam antibiotic, is commonly used to treat various infectious diseases. This drug has been reported to be unstable depending on pH and temperature. Also, magnesium oxide (MgO) is a typical alkaline drug frequently prescribed as a laxative. These drugs are occasionally taken together, particularly by older patients. In this study, we have investigated the chemical stability of cefaclor in a concomitant simple suspension with MgO. A cefaclor capsule with or without an MgO tablet was subjected to the simple suspension method, and the suspensions were analyzed by high-performance liquid chromatography. No degradation was observed for the suspension of cefaclor alone, whereas when concomitantly suspended with MgO, the peak intensity of cefaclor considerably decreased, and two degradation peaks appeared. The results showed that co-suspensions with MgO should be avoided. The degradation products were isolated and spectroscopically identified to be piperazine derivatives including a novel one. Their plausible formation mechanisms have also been proposed.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 2","pages":"Article 104063"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145523628","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}