Journal of pharmaceutical sciences最新文献_第4页

3D printing for personalized formulations: individual dosing strategies for propranolol hydrochloride tablets 3D打印个性化配方：盐酸心得安片的个人剂量策略。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-05-08 DOI: 10.1016/j.xphs.2025.103816

Yingjun Xiao , Xiaolu Han , Yunqi Bi , Xiaoxuan Hong , Xianfu Li , Nan Liu , Shanshan Yang , Hui Zhang , Zengming Wang , Aiping Zheng

{"title":"3D printing for personalized formulations: individual dosing strategies for propranolol hydrochloride tablets","authors":"Yingjun Xiao , Xiaolu Han , Yunqi Bi , Xiaoxuan Hong , Xianfu Li , Nan Liu , Shanshan Yang , Hui Zhang , Zengming Wang , Aiping Zheng","doi":"10.1016/j.xphs.2025.103816","DOIUrl":"10.1016/j.xphs.2025.103816","url":null,"abstract":"<div><div>3D printing technology is characterized by highly personalized, small batch production, and excellent reproducibility. These features enable it to address the limitations of traditional dose-dividing methods currently employed in medical institutions, thereby fulfilling the diverse dosing requirements of patients. In this study, we developed two individual dosing strategies for formulating 3D printing pharmaceutical formulations (3DPF) and 3D printing divided-dose tablets (3DPDT). Specifically, 3DPF were prepared using a gel ink containing propranolol hydrochloride as the active pharmaceutical ingredient, while 3DPDT were fabricated using a paste ink incorporating powdered commercial tablets. We investigated the rheological properties of the gel and paste ink, and assessed the mechanical properties, assay, and dissolution profile of tablets. The results indicate that the appearance, mechanical properties, drug content, content uniformity and drug dissolution rate of 3DPF and 3DPDT meet the United States Pharmacopoeia-National Formulary 2024 (USP-NF 2024) requirements. These strategies demonstrate highly reproducible and high-quality tablet preparation capabilities, which are applicable in drug development and pharmacy services. Furthermore, these approaches effectively resolve the issue of fixed dosages in commercially available drugs failing to meet the personalized medication needs of special populations. They provide a novel and promotable individual dosing solution tailored to the medication requirements of various patient groups.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 7","pages":"Article 103816"},"PeriodicalIF":3.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972670","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

A cluster of articles in memory of Rodolfo Pinal, Ph.D. 纪念鲁道夫·皮纳尔博士文集

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-05-07 DOI: 10.1016/j.xphs.2025.103821

Hwee Jing Ong, Fernando Alvarez-Nunez, Teresa Carvajal, Samuel H Yalkowsky

引用次数: 0

Factorial design, formulation, in vitro and in vivo evaluation of a multi-layer tablet containing ticagrelor and aspirin, for dual antiplatelet therapy 含有替格瑞洛和阿司匹林的多层片剂用于双重抗血小板治疗的析因设计、配方、体外和体内评价

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-05-07 DOI: 10.1016/j.xphs.2025.103817

Mahmoud Mostafa , Osama M. Sayed , Mahmoud Hasan Teaima , Mohamed Ahmed El-Nabarawi , Mohamed Yasser

{"title":"Factorial design, formulation, in vitro and in vivo evaluation of a multi-layer tablet containing ticagrelor and aspirin, for dual antiplatelet therapy","authors":"Mahmoud Mostafa , Osama M. Sayed , Mahmoud Hasan Teaima , Mohamed Ahmed El-Nabarawi , Mohamed Yasser","doi":"10.1016/j.xphs.2025.103817","DOIUrl":"10.1016/j.xphs.2025.103817","url":null,"abstract":"<div><div>Dual antiplatelet therapy regimen is used for the management of acute coronary syndrome. To investigate the potential for combining ticagrelor and aspirin into a single-dose alternative for dual antiplatelet therapy, a factorial design (3<sup>2</sup>) was applied to the formulation of a multi-layer tablet containing both drugs, each in a separate layer. The design focused on three levels, of two categorical independent factors: the type of disintegrant used in ticagrelor layer and the type used in aspirin layer. Their effects were analyzed on three dependent responses: tablet hardness, disintegration time, and in vitro drug release. The experimental design, data analysis and formulation optimization were implemented using Design-Expert® software, which identified formulation (F5), with croscarmellose sodium, the disintegrant in ticagrelor layer, and pregelatenized starch, the disintegrant in aspirin layer, as an optimized formulation. F5 displayed tablet hardness of 7.30 ± 0.37 kp, disintegration time of 122 ± 3.3 s, and in vitro drug release of 90.77 % after 30 min, resulting in a desirability score of 0.873. The optimized formulation then showed stability for three months, at 40 ºC and 75 % relative humidity, and demonstrated a significant increase in bleeding time, comparable to that of commercial multi dose regimen, in the in vivo assessment using rabbit cuticle bleeding time method, providing a valuable alternative, for dual antiplatelet therapy regimens, that is expected to reduce healthcare costs and enhance the compliance of acute coronary syndrome patients.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 7","pages":"Article 103817"},"PeriodicalIF":3.7,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143946827","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 the suitability of utilizing plasma concentration as a surrogate to understand lung exposure of inhaled drug in rats: Different delivery methods of fluticasone propionate 用血药浓度作为替代物了解大鼠吸入药物肺暴露的适宜性研究：丙酸氟替卡松不同给药方式。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-05-03 DOI: 10.1016/j.xphs.2025.103806

Po-Chang Chiang , Cornelia H. Rinderknecht , Jia Liu , Karthik Nagapudi , Matthew R. Durk

{"title":"Investigation of the suitability of utilizing plasma concentration as a surrogate to understand lung exposure of inhaled drug in rats: Different delivery methods of fluticasone propionate","authors":"Po-Chang Chiang , Cornelia H. Rinderknecht , Jia Liu , Karthik Nagapudi , Matthew R. Durk","doi":"10.1016/j.xphs.2025.103806","DOIUrl":"10.1016/j.xphs.2025.103806","url":null,"abstract":"<div><div>Pulmonary diseases, such as asthma and chronic obstructive pulmonary disease (COPD) are complex human airway diseases that affect millions of people worldwide. A topical drug delivery system such as a dry powder inhaler (DPI) is often used to deliver the drug directly to airways to increase the therapeutic index; however, accurately predicting the efficacy and pharmacokinetics of new molecular entities remains challenging, in particular, estimating the effective drug concentration at the site of action. This is of critical importance since many inhaled drugs are designed to have topical-only efficacy to reduce systemic side effects. Preclinically, drug delivery in rodents now focuses on mimicking the clinical dosing regimen, coupled with modeling approaches to better understand the lung PK/PD relationship. One modeling approach is the use of the systemic exposure to predict the drug concentration and release from the lung as the first step to model the lung PK/PD. With a tool compound, fluticasone propionate, the authors used a Loo-Riegelman-based pharmacokinetic analysis and compared several methods of dosing to rats to evaluate the suitability of using the systemic exposure to estimate the amount of drug absorbed by the lung. The Loo-Riegelman approach predicted lung absorption well in humans following DPI dosing. In rats, lung absorption was predicted well for IT dosing, but not DPI dosing, emphasizing caution in using systemic drug concentrations to predict lung concentrations in rats receiving a DPI dose.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 7","pages":"Article 103806"},"PeriodicalIF":3.7,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988118","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

Revisiting ligand-exchange chromatography for valsartan chiral analysis using a conventional non-chiral column 用传统非手性色谱柱重述配体交换色谱法进行缬沙坦手性分析。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-05-03 DOI: 10.1016/j.xphs.2025.103797

Chanbopha Tho , Sean M. Kerwin , Promporn Jamnongtanachot , Vorasit Vongsutilers , Bodin Tuesuwan

{"title":"Revisiting ligand-exchange chromatography for valsartan chiral analysis using a conventional non-chiral column","authors":"Chanbopha Tho , Sean M. Kerwin , Promporn Jamnongtanachot , Vorasit Vongsutilers , Bodin Tuesuwan","doi":"10.1016/j.xphs.2025.103797","DOIUrl":"10.1016/j.xphs.2025.103797","url":null,"abstract":"<div><div>As the chiral drug market grows, developing efficient separation methods while ensuring quality has become a key focus for the pharmaceutical industries. Chiral column chromatography is effective but often impractical due to its expense. In our research, we established a cost-effective chiral analysis method for valsartan using ligand-exchange chromatography (LEC), an underutilized yet promising analytical technique with significant potential for further development in pharmaceutical research. This approach allows separation on a non-chiral column by forming complexes with metal ions in the mobile phase. Valsartan, a widely used antihypertensive drug, and its enantiomeric impurity were analyzed through LEC on a C<sub>18</sub> column. We optimized the conditions for chiral selectors, copper ions, and pH, achieving a resolution exceeding 2.7. The method, validated per ICH Q2(R1) guidelines for assay and impurity determination, exhibited outstanding linearity (r² > 0.999) and recovery (97.8 %–101.7 %), ensuring a complete separation of the target peak, even after forced degradation. LEC presents a cost-effective alternative for in-house chiral drug analysis, addressing the challenges posed by limited access to chiral columns in countries focused on local generic drug production, and offering a practical solution to the increasing global demand for efficient chiral separation.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 7","pages":"Article 103797"},"PeriodicalIF":3.7,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064017","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

Vitamin C reduces gastric pH in pharmacologically induced hypochlorhydria: a potential approach for mitigating pH-dependent drug-drug interactions of weak-base drugs. 维生素C在药理学诱导的次氯酸中降低胃pH值：一种减轻弱碱药物的pH依赖性药物-药物相互作用的潜在方法。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-05-03 DOI: 10.1016/j.xphs.2025.103809

Hala M Fadda, Andrea Shin, Mohammed Rayyan Waseem, Michael Camilleri

{"title":"Vitamin C reduces gastric pH in pharmacologically induced hypochlorhydria: a potential approach for mitigating pH-dependent drug-drug interactions of weak-base drugs.","authors":"Hala M Fadda, Andrea Shin, Mohammed Rayyan Waseem, Michael Camilleri","doi":"10.1016/j.xphs.2025.103809","DOIUrl":"10.1016/j.xphs.2025.103809","url":null,"abstract":"<p><p>Orally administered, poorly soluble, weak-base drugs are subject to gastric pH-dependent drug-drug interactions which can be clinically significant. Proton pump inhibitors (PPIs) have been shown to reduce the bioavailability of kinase inhibitors, antivirals and triazole antifungals, through elevation of gastric pH. The objective of this study was to determine if chewable ascorbic acid (AA) tablets can induce a transient reduction in gastric pH. Healthy volunteers were pretreated with 20 mg omeprazole to induce hypochlorhydria. On the study day, gastric pH was continuously monitored using a catheter-based pH monitoring system. A pH electrode was transnasally placed in the stomach fundus and pH data was collected in real time. 1000 mg AA chewable tablets were ingested by the study participants with 240 mL of water. In five out of six subjects, a significant drop in gastric pH was observed. A mean (± SD) drop in pH of 3.7 (± 1.8) upon AA intake was observed and time taken to reach lowest gastric pH was 91.2 (± 64) min. Area under the pH versus time curve (AUC<sub>pH</sub>), below median pH over 15 min duration before AA intake, was determined to be 186.8 ± 136.7 (ΔpH.min). This pilot study demonstrates that 1000 mg of AA tablets can significantly reduce gastric pH in individuals receiving treatment with PPIs, providing a potential approach for mitigating pH-dependent drug-drug interactions of weak-base drugs.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"103809"},"PeriodicalIF":3.7,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144016530","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

Near UV and visible light-induced site-specific fragmentation of IgG1-based modalities mediated by histidine and Fe(III): a role for intra-domain interactions? 由组氨酸和铁介导的近紫外和可见光诱导的基于igg1的位点特异性断裂（III）：域内相互作用的作用？

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-05-03 DOI: 10.1016/j.xphs.2025.103810

Maribel Espinoza Ballesteros, Thomas Tolbert, Christian Schöneich

{"title":"Near UV and visible light-induced site-specific fragmentation of IgG1-based modalities mediated by histidine and Fe(III): a role for intra-domain interactions?","authors":"Maribel Espinoza Ballesteros, Thomas Tolbert, Christian Schöneich","doi":"10.1016/j.xphs.2025.103810","DOIUrl":"10.1016/j.xphs.2025.103810","url":null,"abstract":"<div><div>Photo-stability represents a critical quality attribute for the development of therapeutic proteins where the exposure to near UV or visible light can lead to protein fragmentation. Here, we compare the photo-stability of three IgG1 based modalities, formulated in histidine (His) buffer containing various levels of Fe(III). We report a significant difference in the extent of photo-degradation between a high mannose Fc fragment (HM-Fc), NISTmAb and a fusion protein, Flt-3L-Ig. Our results indicate that despite preserving the Fc domain sequence, the NISTmAb and Flt-3L-Ig are more susceptible to site-specific Thr<sup>259</sup> photo-fragmentation in the CH2 domain compared to the HM-Fc (amino acid numbering based on the NISTmAb sequence). Enzymatic deglycoslyation enhanced the susceptibility of both NISTmAb and HM-Fc to photo-fragmentation, while enzymatic cleavage of the Fab domain from NISTmAb decreased the extent of photo-fragmentation. Our findings suggest that differences in photo-stability may be attributed to differences in domain-domain interactions, glycan structure, and the thermal stability of these modalities. Therefore, careful consideration should be given to photostability studies during the development of such proteins into therapeutic drug products.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 7","pages":"Article 103810"},"PeriodicalIF":3.7,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024288","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

Assessing the impact of viscosity lowering excipient on liquid-liquid phase separation for high concentration monoclonal antibody solutions 评价降粘辅料对高浓度单克隆抗体液-液分离的影响

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-05-02 DOI: 10.1016/j.xphs.2025.103804

Chelsea R. Thorn , Deep Bhattacharya , Lindsey Crawford , Vicky Lin , Advait Badkar , Parag Kolhe

{"title":"Assessing the impact of viscosity lowering excipient on liquid-liquid phase separation for high concentration monoclonal antibody solutions","authors":"Chelsea R. Thorn , Deep Bhattacharya , Lindsey Crawford , Vicky Lin , Advait Badkar , Parag Kolhe","doi":"10.1016/j.xphs.2025.103804","DOIUrl":"10.1016/j.xphs.2025.103804","url":null,"abstract":"<div><div>With continued interest in high concentration monoclonal antibody drug products to meet subcutaneous administration requirements, there is heightened attention on balancing protein-protein interactions, solution properties and overcoming instabilities such as increased in viscosity, particle formation, loss in potency, and aggregation of drug products. L-arginine hydrochloride is a commonly used viscosity reducing excipient used to influence protein-protein interactions of high concentration of mAbs. Contrary to literature, we observed that slight modifications to L-arginine hydrochloride concentrations in model drug product formulations can result in liquid-liquid phase separation if excipient and pH conditions are not well tightly controlled. We utilized a biophysical toolkit to assess the potentials of liquid-liquid phase separation (LLPS) that informs the limits of excipient and pH levels using structural- and molecular interaction-based assessments. While liquid-liquid phase separation observed in this study is reversible and does not impact inherent protein folding and structure, we demonstrated that increased ionic content in the formulations can significantly alter the balance of osmolarity toward the occurrence of LLPS. The aim of this work is to demonstrate the diversity of the toolbox used to evaluate the observed LLPS and the decision-making for optimization of formulation development.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 7","pages":"Article 103804"},"PeriodicalIF":3.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143946966","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

Professor Rodolfo Pinal: A man of the Tao. 鲁道夫·皮纳尔教授：一个有道的人。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-05-01 DOI: 10.1016/j.xphs.2025.103808

Kinam Park

引用次数: 0

Evaluating the utility of endogenous OCT2 and MATE1/2-K biomarkers for DDI assessment in early clinical settings. 评估内源性OCT2和MATE1/2-K生物标志物在早期临床环境中评估DDI的效用。

IF 3.7 3区医学

Journal of pharmaceutical sciences Pub Date : 2025-04-30 DOI: 10.1016/j.xphs.2025.103776

Rina Nishii, Yongjun Xue, Runlan Huo, Jian Chen, Hong Shen, Yizhe Chen, Ken Ogasawara

{"title":"Evaluating the utility of endogenous OCT2 and MATE1/2-K biomarkers for DDI assessment in early clinical settings.","authors":"Rina Nishii, Yongjun Xue, Runlan Huo, Jian Chen, Hong Shen, Yizhe Chen, Ken Ogasawara","doi":"10.1016/j.xphs.2025.103776","DOIUrl":"https://doi.org/10.1016/j.xphs.2025.103776","url":null,"abstract":"<p><p>With growing interest in a biomarker-based approach for drug-drug interaction (DDI) predictions, creatinine, N1-methylnicotinamide (NMN), and N1-methyladenosine (m<sup>1</sup>A) have been identified as endogenous substrates of organic cation transporter (OCT) 2 and multidrug and toxin extrusion (MATE) 1/2-K, though clinical validation remains limited. This study builds on recent advancements by evaluating these biomarkers retrospectively using samples from a clinical pharmacology study that assessed DDI via renal cationic transporters between fedratinib (inhibitor) and metformin (substrate) in healthy participants. Fedratinib reduced renal clearance for all endogenous substrates, with m<sup>1</sup>A (38 %) and NMN (36 %) showing reductions comparable to metformin (40 %), while creatinine exhibited slightly lower (29 %), likely reflecting its limited contribution to transporter-mediated renal tubular secretion. Simulations focused on m<sup>1</sup>A due to its favorable characteristics over NMN, particularly its minimal diurnal and intra-participant variability, demonstrating that reliable DDI assessments can still be achieved despite sampling constraints typical in oncology settings. Collectively, our study supports the predictive capabilities of endogenous substrates as biomarkers for renal cation transporter inhibition, with m<sup>1</sup>A in particular showing promise for early DDI assessments in the Phase 1 studies.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"103776"},"PeriodicalIF":3.7,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187214","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