Journal of pharmaceutical sciences最新文献

{"title":"Exploring the antidiabetic effect of various therapeutic essential oils synergistically with repaglinide","authors":"Omnia M. Sarhan ,&nbsp;Samaa O. Abdelqader ,&nbsp;Mostafa S.A. Mostafa ,&nbsp;Manar A.E. Badawi ,&nbsp;Mohamed A.M. Ahmed ,&nbsp;Waleed G.A. El Sayed ,&nbsp;Mostafa I. Gebril","doi":"10.1016/j.xphs.2025.103721","DOIUrl":"10.1016/j.xphs.2025.103721","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to evaluate the antidiabetic efficacy of microemulsions formulated with cardamom oil, black seed oil, and olive oil. The goal was to determine the optimal formulation for stable microemulsions and assess their potential as innovative drug delivery systems for the antidiabetic drug repaglinide.</div></div><div><h3>Methods</h3><div>Initial phase diagrams were constructed to identify the optimal ratios of oil, water, surfactant (Tween 80), and cosurfactant (ethanol) for producing stable microemulsions. The physical attributes of the resulting formulations, such as droplet size, zeta potential, and morphology, were characterized using transmission electron microscopy. Drug release profiles of microemulsions containing repaglinide were evaluated using the dialysis method. Moreover, vivo studies were conducted to assess the therapeutic efficacy of cardamom oil microemulsions compared to standard commercial repaglinide formulations.</div></div><div><h3>Results</h3><div>Microemulsions exhibited suitable properties with optimal particle size, well-defined spherical droplets, and optimized zeta potential. Drug release studies indicated that cardamom oil-based microemulsions demonstrated superior release characteristics, providing a more sustained and controlled release of repaglinide compared to microemulsions containing black seed or olive oil. In vivo studies revealed a significant improvement in antidiabetic outcomes with cardamom oil microemulsions over standard commercial repaglinide formulations. The enhanced efficacy was attributed to improved bioavailability and the controlled release properties of the drug.</div></div><div><h3>Conclusion</h3><div>This research underscores the potential of cardamom oil-based microemulsions as effective antidiabetic drug delivery systems. With superior physicochemical properties and controlled release profiles, they promise innovative treatment options for diabetes, potentially improving therapeutic outcomes for patients.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 5","pages":"Article 103721"},"PeriodicalIF":3.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586099","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":"Ezetimibe alters micelle structure and reduces Niemann-Pick C1-like 1-mediated absorption of vitamins E and K1 in CaCo-2 cells","authors":"Hideki Aizawa","doi":"10.1016/j.xphs.2025.103712","DOIUrl":"10.1016/j.xphs.2025.103712","url":null,"abstract":"<div><div>Ezetimibe (EZE) is known to inhibit cholesterol absorption by targeting Niemann-Pick C1-like 1 (NPC1L1). However, its effects on the absorption of fat-soluble vitamins, such as Vitamin E and Vitamin K₁, remain unclear. This study investigates how EZE impacts micellar properties and vitamin absorption. We analyzed the shape, size, diffusion rate, and zeta-potential of micelles during Vitamin E and K₁ absorption. Our findings demonstrate that EZE causes micelles to transition from an elliptical to a cylindrical shape, reducing vitamin absorption efficiency. EZE also impairs absorption by altering micelle composition, hindering NPC1L1 binding, and directly blocking vitamin uptake. EZE negatively affects Vitamin E and K₁ absorption, raising concerns about potential deficiencies with long-term use. These findings highlight the need for strategies to minimize the adverse effects of EZE in clinical practice.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 5","pages":"Article 103712"},"PeriodicalIF":3.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586101","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 development of liposome nanoparticles encapsulated with yam polysaccharide.","authors":"Yuehan Cui, Meng Song, Ruilai Liu, Zhenhao Xi, Ling Zhao, Lian Cen","doi":"10.1016/j.xphs.2025.103718","DOIUrl":"10.1016/j.xphs.2025.103718","url":null,"abstract":"<p><p>A novel liposome nanoparticle loaded with yam polysaccharide was developed in this study via a tailor-made microfluidic device and further optimized through the Box-Behnken Design method of surface analysis to exploit combinational immunomodulatory effects of liposomes and yam polysaccharide. A chip of 100 μm in height and 200 μm in width with a mixing channel with embedded baffles to enhance fluid mixing was first designed and fabricated. Liposome nanoparticles were obtained by manipulating the operating parameters of the microfluidic chip. The formulation of yam polysaccharide loaded liposomes (YPL¹) was optimized using response-surface analysis, and their physicochemical properties were characterized. In vitro cellular assays were performed to assess the effect of YPL on the activity of mouse dendritic cells (DC) and the secretion of immune-related cytokines to investigate the immune-enhancing effect of YPL in vitro. The resulting YPL had a mean size of 154.2±3.8 nm with a narrow size distribution (PDI=0.083) and had a high entrapment efficiency (EE) of 79.02 %. The YPL exhibited good stability at 4 °C over 14 days of storage, and an in vitro sustained release duration of approximately 30 h. The YPL demonstrated excellent biocompatibility and stimulated the expression of immune-related cytokines, especially TNF-α. Therefore, the YPL with well controlled particle size and high loading capacity, capable of exhibiting potent immunostimulatory activity was successfully developed in this study via a microfluidic device and optimized using response-surface analysis. The current YPL engineering methodology could further serve as an experimental platform for liposome nanoparticle development.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"103718"},"PeriodicalIF":3.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586105","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":"Physiologically-based modeling of methylprednisolone pharmacokinetics across species with extrapolations to humans","authors":"Ruihong Yu,&nbsp;William J. Jusko","doi":"10.1016/j.xphs.2025.103719","DOIUrl":"10.1016/j.xphs.2025.103719","url":null,"abstract":"<div><div>Methylprednisolone (MPL) is widely used in clinical and veterinary medicine to manage inflammation. Plasma profiles and PK parameters in 7 species were digitized from 10 literature sources along with our recent PBPK results in rats. Basic allometric scaling provided reported clearance (<em>CL</em>) and distribution volume (<em>V_d</em>) from noncompartmental analysis highly correlated with body weights (R² &gt; 0.96), although rat <em>CL</em> deviated from the linear trend. A basic nonlinear minimal physiologically-based pharmacokinetic model (mPBPK) (Model I), an intermediate reversible-metabolism mPBPK model (Model II) accounting for MPL and methylprednisone interconversion, and a full highly complex PBPK model were used to assess the interspecies plasma concentration datasets. The MPL PK profiles were reasonably captured by Model I and II, yielding allometric exponents for <em>CL</em> of 1.15 and 0.94, consistent with basic allometry, 1.18. Rat PK informed the presence of nonlinear tissue binding and required an adjustment factor approximately 8-fold higher for its <em>CL</em>. Our full PBPK model was extrapolated from rats to humans using allometry from Model II and optimized producing excellent applications in healthy subjects and patients. This study, based on conserved tissue binding properties, provided three allometric translational PBPK models for MPL, facilitating reasonable PK assessment and interpretation for various species.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 5","pages":"Article 103719"},"PeriodicalIF":3.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586108","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":"AI-enhanced X-ray microscopy for non-destructive detection, quantification, and particle size analysis of crystalline miconazole in amorphous solid dispersions","authors":"Yongan Tang ,&nbsp;Isha Bordawekar ,&nbsp;Adam J. Zaczek ,&nbsp;Andrew D. Vogt","doi":"10.1016/j.xphs.2025.103720","DOIUrl":"10.1016/j.xphs.2025.103720","url":null,"abstract":"<div><div>In the pharmaceutical industry, amorphous solid dispersions (ASDs) are commonly utilized to enhance the solubility and bioavailability of poorly soluble active pharmaceutical ingredients (APIs). Polymers such as copovidone are also frequently employed as stabilizing agents in ASDs due to their ability to reduce the thermodynamical instability of the amorphous form compared to their crystalline form. Detecting and measuring any crystalline API particles present in the ASD formulation is critical for ensuring drug efficacy and stability. In this study, ASD tablets miconazole in a copovidone matrix spiked with known concentration of crystalline miconazole were characterized by X-ray microscopy (XRM). We demonstrate how XRM combined with AI-assisted image segmentation can provide quantitative characterization of crystalline particles, including detailed particle size distribution (PSD) information. The AI-assisted image processing model was found to be robust, reducing human error associated with traditional threshold selection. Additionally, we evaluated particle size changes from the blend to the final drug product to understand how the API and excipient behave during tablet manufacturing. This approach has broader applications in drug product development, particularly in monitoring recrystallization and evaluating process-induced changes during blending and compression.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 5","pages":"Article 103720"},"PeriodicalIF":3.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573325","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":"Transportation of protein drugs at hospital: Comparison of mechanical stress occurring during pneumatic transportation and hand-carried transport.","authors":"Pauline Barreau, Fréderic Feutry, Marie Abelé, Alexandre Villain, Ilyes Sakji, Guillaume Marliot","doi":"10.1016/j.xphs.2025.103715","DOIUrl":"10.1016/j.xphs.2025.103715","url":null,"abstract":"<p><p>In this study, we quantitatively characterize the mechanical shock generated in the pneumatic transport systems (PTS) in our center, determine the PTS pipeline with the highest risk of mechanical stress, and compare these results with hand-carried transport by trolleys or transportation boxes. Acceleration measurements were performed in triplicate for each of the five departments using a 3-axis accelerometer, which was fixed to three distinct experimental bags and a syringe. We measured the area under the curve (AUC) of the acceleration distribution with a threshold of 2 g, and the number of acceleration peaks (NAP) from >3 to 15 g-forces. The data obtained were calculated using bilateral Wilcoxon-Mann-Whitney non-parametric tests. The AUC and NAP_3-15 g-forces for PTS were significantly greater than those for hand-carried transport by trolley and box (p < 0.001), which did not show any peak above the NAP₁₀. The PTS pipeline with more curves and redirection airlocks had the highest risk of mechanical stress, whereas no difference was observed per type of container. Transport by trolley had significantly greater (p < 0.001) AUC, NAP₃, and NAP₅ than by box. Our results indicate that there is greater mechanical stress arising during PTS transportation than during hand-carried transport, preferentially in transportation boxes.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"103715"},"PeriodicalIF":3.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573343","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":"Corrigendum to “Review on 505(b)(2) Drug products approved by USFDA from 2010 to 2020 emphasizing intellectual property and regulatory considerations for reformulations and new combinations” [Journal of Pharmaceutical Sciences/ Volume 112, Issue 8, August 2023/ Pages 2146-2175]","authors":"Jyosna Devi Ravula ,&nbsp;Ramakrishna Nirogi ,&nbsp;Manthan D. Janodia","doi":"10.1016/j.xphs.2025.103716","DOIUrl":"10.1016/j.xphs.2025.103716","url":null,"abstract":"","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 4","pages":"Article 103716"},"PeriodicalIF":3.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573333","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":"Potential risk factors of protein aggregation in syringe handling during antibody drug dilution for intravenous administration","authors":"Masakazu Fukuda ,&nbsp;Shino Nagae ,&nbsp;Toru Takarada ,&nbsp;Satoshi Noda ,&nbsp;Shin-ya Morita ,&nbsp;Masafumi Tanaka","doi":"10.1016/j.xphs.2024.12.029","DOIUrl":"10.1016/j.xphs.2024.12.029","url":null,"abstract":"<div><div>Protein aggregation, a major concern in biopharmaceutical quality control, can be accelerated by various stresses during clinical handling. This study investigated potential aggregation risk factors during dilution process with syringe handling for intravenous administration. Using γ-globulin and IgG solutions as surrogate models of antibody therapeutics, we examined the effects of high sliding speeds and piston operations of the syringe on protein aggregation during saline dilution. Our results revealed that elevated sliding speeds promoted proteinaceous subvisible and/or visible particle formation, which was further enhanced by piston operations. The proteinaceous particle formation was presumed to be caused by fine air bubbles generated due to rapid pressure changes arising from shear stress during needle passage. While polysorbate 20 effectively suppressed the particle formation induced by the syringe handling at sufficient concentrations, its protective effect became inadequate under high dilution conditions, as exemplified by those encountered in low-body-weight patient protocols. Different proteins exhibited varying susceptibility to the syringe-induced aggregation. These findings demonstrate that the combination of syringe handling and dilution conditions could significantly impact protein stability during clinical handling, particularly for less stable biopharmaceuticals. A deeper understanding of these factors is crucial for developing more robust formulations and establishing safer handling practices for biopharmaceuticals.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 3","pages":"Pages 1625-1638"},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038662","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":"Risk assessment and management strategy of two new NDSRIs in a pharmaceutical drug product for the treatment of a rare disease: From prediction to control","authors":"Partha Mukherjee,&nbsp;Xin Yao,&nbsp;Sheela Sitaraman,&nbsp;Jeff Castelli,&nbsp;Jon Brudvig,&nbsp;Saroj Ramdas","doi":"10.1016/j.xphs.2025.01.016","DOIUrl":"10.1016/j.xphs.2025.01.016","url":null,"abstract":"<div><div>N-nitrosamines are a class of compounds belonging to the “cohort of concern” and characterized by the linkage of a nitroso group (-N=O) to an amine functional group (-NR₂). Some of these compounds are mutagenic, genotoxic, and potentially carcinogenic agents in humans, which necessitates control at acceptable safe levels. The current work presents a comprehensive risk assessment and mitigation strategy for two complex diastereomeric nitrosamines as New Drug Substance Related Impurities (NDSRIs) for miglustat 65mg capsules. A sequential risk assessment and management strategy was executed, which included predictive chemistry of formation, organic synthesis, and in-silico mutagenic and carcinogenic risk assessments. These activities were followed by the application of a highly sensitive validated analytical method with a Limit of Quantitation of 6.9 ppb for the combined NDSRIs. Confirmatory testing of three drug product batches were performed as per regulatory requirements to verify adherence to a conservative Acceptable Intake Limit of 18 ng/day for the combined NDSRIs.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 3","pages":"Pages 1572-1582"},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066306","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":"Obtaining heat transfer coefficients (Kv) distribution directly from mass flow measurements during the sublimation step of freeze-drying","authors":"Jean-René Authelin ,&nbsp;Benoit Koumurian ,&nbsp;Lauren Fontana ,&nbsp;Sharon Batelu ,&nbsp;Kanika Sarpal ,&nbsp;Mostafa Nakach ,&nbsp;Lionel Gerbeau ,&nbsp;Bertrand Woinet","doi":"10.1016/j.xphs.2025.01.027","DOIUrl":"10.1016/j.xphs.2025.01.027","url":null,"abstract":"<div><div>The knowledge of heat transfer coefficients (K_v) and their distribution is a crucial element in the successful transfer of a freeze-drying process to a new piece of equipment. Nevertheless, the implementation of the classical ice sublimation method is resource consuming, particularly in the industrial context, which represents a significant barrier to its application. This paper demonstrates that the K_v distribution can be calculated from the measurement of mass flow during a freeze-drying operation by reversing the results of process simulation calculations. This methodology works independently of the experimental method used to measure the mass flux: tunable diode laser absorption, inlet/outlet temperature difference of the shelves, or chamber/ condenser pressure difference. The advantage of this new method is that it requires no specific experimental effort and can be carried out on routine production runs (especially with the temperature or pressure difference methods), provided the freeze drier possesses at least shelf inlet/outlet temperature measurement and/or chamber and condenser capacitance pressure measurement. Furthermore, the measurement encompasses all vials, which is not achievable using the conventional method for commercial units that contain tens of thousands of vials. Once fed back into the primary drying mechanistic model, the K_v distribution is used to estimate the temperature distribution in the product.</div><div>In this article, we provide practical examples at all scales, from laboratory to industrial production.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 3","pages":"Pages 1597-1604"},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080432","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}