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Corrigendum to “Evaluation of Mechanical Properties of TiO2-free Tablet Coatings” [Journal of Pharmaceutical Sciences/ Volume 114, Issue 10, 10 2025, 103942] “评价无二氧化钛片剂包膜的机械性能”的勘误表[医药科学杂志/ 114卷,第10期,10 2025年,103942]。
IF 3.8 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2025-12-01 DOI: 10.1016/j.xphs.2025.103970
Mohammad Khalid , Viplav K. Bhondekar , Krishnayan Haldar , Mahesh S. Tirumkudulu , Kenneth S. Ogueri , Alfred Berchielli , Geoff McKee , Pankaj Doshi
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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 3.8 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2025-12-01 DOI: 10.1016/j.xphs.2025.103809
Hala M. Fadda , Andrea Shin , Mohammed Rayyan Waseem , Michael Camilleri
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 (AUCpH), 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.
口服,难溶,弱碱药物受胃ph依赖的药物-药物相互作用,这可能具有临床意义。质子泵抑制剂(PPIs)已被证明可以通过升高胃ph来降低激酶抑制剂、抗病毒药物和三唑类抗真菌药物的生物利用度。本研究的目的是确定咀嚼抗坏血酸(AA)片是否可以诱导胃ph的短暂降低。健康志愿者用20mg奥美拉唑预处理以诱导次氯酸。在研究当天,使用基于导管的pH监测系统连续监测胃pH。经鼻将pH电极置于胃底,实时收集pH值数据。研究参与者用240毫升水吞下1000毫克AA咀嚼片。在6名受试者中,有5名观察到胃pH值显著下降。摄入AA后,pH值平均(±SD)下降3.7(±1.8),达到最低胃pH值所需的时间为91.2(±64)分钟。摄入AA前15分钟内pH值低于中位数的时间曲线下面积(AUCpH)为86.8±136.7 (ΔpH.min)。本初步研究表明,1000 mg AA片可显著降低PPIs治疗个体的胃pH值,为减轻弱碱药物的pH依赖性药物-药物相互作用提供了一种潜在的途径。
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引用次数: 0
Enhancing drug solubilization using a surface-modified edible biopolymer through hot melt extrusion: A design space methodology 通过热熔挤压提高表面改性可食用生物聚合物的药物增溶性:一种设计空间方法。
IF 3.8 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2025-12-01 DOI: 10.1016/j.xphs.2025.103956
Hwee Jing Ong , Fernando Alvarez-Nunez , Rodolfo Pinal
This study investigates the use of an octenylsuccinate-modified dendrimer-like biopolymer (OS-DLB) as a carrier matrix in the formulation of biodendrimeric solid dispersions (BDSDs) using hot melt extrusion (HME). Ibuprofen (IBU) and griseofulvin (GSF) were selected as model compounds due to their poor aqueous solubility – one limited by its hydrophobicity and the other by its strong crystal lattice, respectively. This study demonstrates that the BDSD formulation can significantly enhance the dissolution rates of the model compounds through a parallel liquid phase equilibrium, while retaining their predominantly crystalline state. Across the 13 runs, IBU BDSDs showed a rapid initial dissolution with inter-batch variability converging by 60 min, whereas GSF BDSDs displayed wider divergence. IBU also underwent some loss of crystallinity due to its miscibility with PLX, a phenomenon not observed for GSF. Using a design space approach, which integrates experimental design, multivariate prediction models, and response surface modeling, the findings reveal that processing temperature, residence time, and screw speed are important factors affecting the dissolution and crystallinity of the BDSDs. The extent of their influence, however, varies depending on the crystal lattice energy and hydrophobicity of the model compounds. The HME design space for producing GSF BDSDs is less sensitive to processing variables than that for IBU BDSDs. For GSF, uniform dispersion of PLX throughout the BDSDs and preservation of OS-DLB structure are key to improving dissolution. In contrast, limited molecular distribution of PLX is crucial to producing IBU BDSDs with high crystallinity.
本研究研究了利用辛烯基琥珀酸修饰的枝状生物聚合物(OS-DLB)作为载体基质,利用热熔挤压(HME)制备生物枝状固体分散体(BDSDs)。选择布洛芬(IBU)和灰黄霉素(GSF)作为模型化合物是因为它们的水溶性较差,一个受疏水性限制,另一个受强晶格限制。本研究表明,BDSD配方可以通过平行液相平衡显著提高模型化合物的溶解速度,同时保持其主要的晶体状态。在13次运行中,IBU BDSDs表现出快速的初始溶解,批间变异性在60分钟内收敛,而GSF BDSDs表现出更大的差异。由于与PLX的混溶,IBU也经历了一些结晶度的损失,而GSF没有观察到这种现象。采用设计空间方法,将实验设计、多元预测模型和响应面建模相结合,研究结果表明,加工温度、停留时间和螺杆转速是影响BDSDs溶出度和结晶度的重要因素。然而,它们的影响程度取决于模型化合物的晶格能和疏水性。生产GSF bdsd的HME设计空间对加工变量的敏感性低于生产IBU bdsd的HME设计空间。对于GSF来说,PLX在BDSD中的均匀分散和保持OS-DLB结构是改善溶解的关键。相反,有限的PLX分子分布对于制备高结晶度的IBU BDSDs至关重要。
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引用次数: 0
Quantitative elucidation of the effect of ordered mixing in pharmaceutical tablets using correlative microscopy-tomography techniques and AI-enabled image analysis 使用相关显微镜断层扫描技术和人工智能图像分析定量阐明药物片中有序混合的影响。
IF 3.8 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2025-12-01 DOI: 10.1016/j.xphs.2025.103955
Yinshan Chen , Sruthika Baviriseaty , Prajwal Thool , Aiden Zhu , Kellie Sluga , Phillip D. Yawman , Shawn Zhang , Chen Mao
In low-dose tablet formulations, achieving content uniformity is of utmost importance. Conventional bulk characterization methods, such as blend uniformity testing, lack the ability to capture the structural and compositional characteristics of API within tablets. To fill this gap, we employed a correlative imaging and analysis workflow that integrates synchrotron X-ray micro-computed tomography (SyncCT), mosaic field-of-view scanning electron microscopy (mSEM), and energy-dispersive X-ray spectroscopy (EDX) methods, combined with AI-enabled image segmentation algorithms. This workflow was utilized to investigate the effect of ordered mixing, introduced by conical screening milling (comilling), on API distribution in two real-world tablets. Specifically, two tablets with identical formulations were prepared; one incorporating comilling and the other without it. The tablets were then subjected to the imaging workflow. The results showed that the comilling process significantly improved the uniformity of API distribution in the tablet through ordered mixing, as evidenced by mSEM-EDX and SyncCT imaging. Furthermore, the API uniformity was achieved without altering the microstructural characteristics, as evidenced by consistent pore size distribution and tortuosity values between the comilled and non-comilled tablets. Overall, this study demonstrated the potential of advanced imaging and AI-based image analysis in facilitating formulation development for low-dose tablets.
在低剂量片剂制剂中,达到含量均匀性是最重要的。传统的散装表征方法,如混合均匀性测试,缺乏捕捉片剂内原料药的结构和组成特征的能力。为了填补这一空白,我们采用了一种相关的成像和分析工作流程,该流程集成了同步加速器x射线微计算机断层扫描(SyncCT)、马赛克视场扫描电子显微镜(mSEM)和能量色散x射线光谱学(EDX)方法,并结合了支持人工智能的图像分割算法。该工作流程被用来研究有序混合的影响,通过锥形筛选研磨(研磨),对原料药分布在两个现实世界的药片。具体而言,制备了两种配方相同的片剂;一种有研磨,另一种没有。然后将这些药片放入成像工作流程中。结果表明,通过mSEM-EDX和SyncCT成像,粉碎过程明显改善了原料药在片剂中有序混合的均匀性。此外,在不改变微结构特征的情况下,原料药的均匀性得以实现,这可以从颗粒与未颗粒之间的孔径分布和扭曲度值的一致中得到证明。总的来说,这项研究证明了先进成像和基于人工智能的图像分析在促进低剂量片剂配方开发方面的潜力。
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引用次数: 0
Phosphatidylserine blockade by dipicolylamine-zinc enhances chemoimmunotherapy of B16F10 melanoma 二聚胺锌阻断磷脂酰丝氨酸增强B16F10黑色素瘤的化学免疫治疗。
IF 3.8 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2025-12-01 DOI: 10.1016/j.xphs.2025.104065
Jianping Wang , Fanfei Meng , Ziang Chen , Yanying He , Jung Suk Kim , Karen Gutierrez Parra , Kunyu Jiang , Trevor G. Sargent , Yoon Yeo
In cancer therapy, chemotherapy and immunomodulatory agents are often combined to leverage their complementary mechanisms. Chemotherapeutic drugs promote the release of tumor antigens in situ, enhancing immune recognition, whereas immunostimulants recruit and activate immune cells. However, chemotherapy also induces externalization of phosphatidylserine (PS) on tumor cells, which interacts with antigen presenting cells (APCs) in the tumor microenvironment (TME) and suppresses their responses to immunostimulants. We hypothesize that chemotherapy-induced PS exposure is a key driver of immunosuppressive TME, and that blocking this effect is essential to enable effective immunostimulation. In this study, we validated that sublethal doses of doxorubicin, a representative chemotherapeutic agent, induce PS externalization on tumor cells, which in turn impairs the responsiveness of APCs to immunostimulants. To counteract chemotherapy-induced PS exposure, we employed zinc-dipicolylamine (DPA-Zn), a cost-effective and commercially available small molecule, as a PS blocking agent. DPA-Zn bound to PS and restored the responsiveness of PS-suppressed APCs to immunostimulants, such as lipopolysaccharide and cyclic dinucleotide (CDN). DPA-Zn enhanced the antitumor activity of doxorubicin and its combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) or CDN in the B16F10 melanoma model. The safety and antitumor activity of this combination were further improved with liposomal formulations of doxorubicin and CDN. These findings identify PS externalization as a mechanism of chemotherapy-induced immunosuppressive TME and demonstrate that targeting PS with DPA-Zn can potentiate chemoimmunotherapy.
在癌症治疗中,化疗和免疫调节剂经常结合起来利用它们的互补机制。化疗药物促进肿瘤抗原的原位释放,增强免疫识别,而免疫刺激剂招募和激活免疫细胞。然而,化疗也会诱导肿瘤细胞上的磷脂酰丝氨酸(PS)外化,与肿瘤微环境(TME)中的抗原呈递细胞(APCs)相互作用,抑制其对免疫刺激物的反应。我们假设化疗诱导的PS暴露是免疫抑制性TME的关键驱动因素,阻断这种作用对于实现有效的免疫刺激至关重要。在这项研究中,我们证实了亚致死剂量的阿霉素(一种代表性的化疗药物)可诱导肿瘤细胞上的PS外化,从而削弱APCs对免疫刺激剂的反应性。为了对抗化疗诱导的PS暴露,我们使用了锌-二聚胺(DPA-Zn),一种具有成本效益和市售的小分子,作为PS阻断剂。DPA-Zn与PS结合,恢复PS抑制的APCs对免疫刺激物(如脂多糖和环二核苷酸(CDN))的反应性。DPA-Zn在B16F10黑色素瘤模型中增强阿霉素及其与粒细胞-巨噬细胞集落刺激因子(GM-CSF)或CDN联合的抗肿瘤活性。阿霉素和CDN的脂质体制剂进一步提高了该组合的安全性和抗肿瘤活性。这些发现确定了PS外化是化疗诱导的免疫抑制性TME的机制,并表明DPA-Zn靶向PS可以增强化学免疫治疗。
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引用次数: 0
Efflux and uptake of androgen sulfates using transporter-overexpressing HEK293 cells and membrane vesicles 转运蛋白过表达HEK293细胞和膜泡对硫酸雄激素的外排和摄取
IF 3.8 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2025-12-01 DOI: 10.1016/j.xphs.2025.103705
Arttu Uoti , Erkka Järvinen , Noora Sjöstedt , Jan Koenderink , Moshe Finel , Heidi Kidron
Hydrophilic steroid conjugates require active and facilitated transport mechanisms for their distribution into tissues and excretion from the body. The ATP-binding cassette (ABC) and solute carrier organic anion (SLCO) transporters involved in androgen sulfate (-S) disposition have been poorly characterized. In this study, we investigated the in vitro transport of testosterone-S, epitestosterone-S, dehydroepiandrosterone-S (DHEA-S), androsterone-S, and etiocholanolone-S by the multidrug resistance-associated proteins 2–4 (MRP2–4, ABCC2–4), breast cancer resistance protein (BCRP, ABCG2), and organic anion-transporting polypeptides (OATP) 1B1, 1B3, and 2B1 (SLCO1B1, SLCO1B3, and SLCO2B1) using human transporter-overexpressing HEK293 cells and membrane vesicles. We found testosterone-S, epitestosterone-S, and DHEA-S to be selectively transported by BCRP and/or MRP4, whereas all studied androgen sulfates were substrates of MRP3, OATP1B1, OATP1B3, and OATP2B1. MRP2 did not transport any of the studied compounds. Evaluation of transport kinetics revealed MRP4 to interact with its substrates at high to moderate affinity, whereas the observed affinities towards MRP3, BCRP, and OATPs were mostly moderate. These results help to build a better mechanistic understanding of the disposition of androgen sulfates in the human body. Additionally, this data may be used to assess the feasibility of androgen sulfates as additional biomarkers in doping detection.
亲水性类固醇偶联物需要积极和便利的运输机制来分布到组织和从体内排泄。atp结合盒(ABC)和溶质载体有机阴离子(SLCO)转运体参与硫酸雄激素(-S)处置的表征很差。在这项研究中,我们研究了在体外通过多药耐药相关蛋白2-4 (MRP2-4、ABCC2-4)、乳腺癌耐药蛋白(BCRP、ABCG2)和有机阴离子转运多肽(OATP) 1B1、1B3和2B1 (SLCO1B1、SLCO1B3和SLCO2B1)在人转运蛋白HEK293细胞和膜泡中转运睾酮- s、表甾酮- s、脱氢表雄酮- s (DHEA-S)、雄酮- s和etiochololone - s的情况。我们发现睾酮- s、表甾酮- s和脱氢表雄酮- s可被BCRP和/或MRP4选择性转运,而所有研究的雄激素硫酸盐都是MRP3、OATP1B1、OATP1B3和OATP2B1的底物。MRP2不转运任何被研究的化合物。转运动力学的评估显示,MRP4与底物的相互作用具有高至中等的亲和力,而对MRP3、BCRP和oatp的亲和力大多为中等。这些结果有助于更好地了解硫酸雄激素在人体内的作用机制。此外,该数据可用于评估雄激素硫酸盐作为兴奋剂检测中额外生物标志物的可行性。
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引用次数: 0
Corrigendum to “Understanding the conditions under which drugs are transferred from the stomach through the upper small intestine after a high-calorie, high-fat meal” [Journal of Pharmaceutical Sciences/ Volume 113, Issue 6, June 2024, Pages 1546-1554] 《了解高热量、高脂肪膳食后药物从胃通过上小肠转移的条件》的勘误表《药物科学杂志》/第113卷,第6期,2024年6月,第1546-1554页。
IF 3.8 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2025-12-01 DOI: 10.1016/j.xphs.2025.103939
Shirin Dietrich , Jens Ceulemans , Eline Hermans , Theodoros Argyropoulos , Konstantinos Goumas , Maria Vertzoni , Christos Reppas
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引用次数: 0
Octenyl succinic anhydride-modified starches as emulsifier agents: A comparative study emphasizing stability, rheology, and emulsion´s microstructure 辛烯基丁二酸酐改性淀粉作为乳化剂:强调稳定性、流变性和乳液微观结构的比较研究。
IF 3.8 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2025-12-01 DOI: 10.1016/j.xphs.2025.103902
Carolina P. Mora , Oscar O. Melo Martínez , Rodolfo Pinal , Claudia E. Mora-Huertas
New alternatives for emulsification are a relevant topic of pharmaceutical research due to the safety concerns of certain materials and the interest in achieving environmentally friendly products. In this sense, this work investigates the performance of five waxy corn starches modified with octenyl succinic anhydride (Hi-Cap® 100, Purity Gum® 2000, Capsul®, N-Creamer® 46, and Purity Gum® Ultra) as emulsifiers, employing caprylic/capric triglyceride as the oily phase and water as the aqueous phase. The type of modified starch influences the droplet size and rheological behavior of emulsions. The systems prepared with N-Creamer® 46 and Purity Gum® Ultra allow the most stable emulsions for 180 days at ∼20 and 40°C ± 0.1°C. The other starches evaluated do not favor the emulsions´ stability, probably due to their lower values of molecular weight, z-average radius of gyration, and dispersed molecular density. Interestingly, the study of the emulsions´ microstructure provides evidence of a three-dimensional starch network around the oil droplets, suggesting the steric effect as the primary mechanism of stabilization when these biopolymers are used. ζ-Potential measurements and the test of electrolyte-induced aggregation corroborate this. These findings contribute to the understanding of how emulsions are stabilized by hydrophobically modified starches, a subject of paramount importance for developing innovative pharmaceutical products.
由于某些材料的安全性问题和对实现环境友好产品的兴趣,乳化的新替代品是制药研究的一个相关主题。在这个意义上,本工作研究了用辛烯基琥珀酸酐(Hi-Cap®100,Purity Gum®2000,Capsul®,N-Creamer®46和Purity Gum®Ultra)作为乳化剂的五种糯玉米淀粉的性能,以癸酸/癸酸甘油三酯为油相,水为水相。变性淀粉的种类影响乳液的液滴大小和流变行为。用N-Creamer®46和Purity Gum®Ultra制备的体系在~ 20和40°C±0.1°C下可保持最稳定的乳剂180天。其他淀粉对乳剂的稳定性不利,可能是由于它们的分子量、z平均旋转半径和分散的分子密度较低。有趣的是,对乳剂微观结构的研究提供了油滴周围三维淀粉网络的证据,表明当使用这些生物聚合物时,立体效应是稳定的主要机制。ζ-电位测量和电解质诱导聚集的测试证实了这一点。这些发现有助于理解疏水改性淀粉如何稳定乳剂,这是开发创新药品的一个至关重要的主题。
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引用次数: 0
Revealing slip behavior in organic molecular crystals: AFM nanoindentation of acetaminophen 揭示有机分子晶体中的滑移行为:对乙酰氨基酚的AFM纳米压痕。
IF 3.8 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2025-12-01 DOI: 10.1016/j.xphs.2025.103972
Yuanyuan Jing , John E. Blendell , M. Teresa Carvajal
Molecular crystals are subjected to mechanical stress that can alter their slip planes which are structural features that play a critical role in governing mechanical behaviors such as milling, that requires fundamental insight for the successful manufacturing and performance of solid oral dosage forms. Milling is a critical unit operation in the manufacturing of pharmaceutical dosage forms. During this process, slip planes may become disrupted and dislocations can form, potentially inducing plastic deformation and significantly altering the physicochemical properties of active pharmaceutical ingredients (API). While slip, a dominant mechanism of plasticity, is well characterized in inorganic crystals, its behavior in organic molecular crystals remains poorly understood due to their low symmetry and anisotropic nature. In this study, we investigate plastic deformation in a model organic crystal, acetaminophen, using atomic force microscopy (AFM) nanoindentation. Distinct pile-up patterns forming parallel facets around indentation sites were observed and systematically analyzed. These pile-ups were experimentally confirmed to align with specific crystallographic slip planes. Based on this, a geometry-based strategy was developed to automatically identify, and index slip planes from indentation pile-up features. This method may offer new insights into the deformation behavior of organic crystals and serves as a broadly applicable tool for investigating slip systems across a wide range of pharmaceutical and molecular materials.
分子晶体受到机械应力,可以改变其滑移面,滑移面是在控制机械行为(如铣削)中起关键作用的结构特征,这需要对固体口服剂型的成功制造和性能有基本的了解。碾磨是制造药物剂型的关键单元操作。在此过程中,滑移面可能会被破坏并形成位错,从而可能引起塑性变形,并显著改变活性药物成分(API)的理化性质。虽然滑移是无机晶体中塑性的主要机制,但由于其低对称性和各向异性的性质,其在有机分子晶体中的行为仍然知之甚少。在这项研究中,我们使用原子力显微镜(AFM)纳米压痕研究了模型有机晶体对乙酰氨基酚的塑性变形。观察并系统分析了在压痕部位周围形成平行面的不同堆积模式。实验证实这些堆积与特定的晶体滑移面对齐。在此基础上,提出了一种基于几何的滑动面自动识别和索引压痕堆积特征的策略。这种方法可以为研究有机晶体的变形行为提供新的见解,并作为一种广泛适用的工具,用于研究各种药物和分子材料的滑移系统。
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引用次数: 0
Crystal defects cause nitrosamine formation in ranitidine under accelerated storage conditions 雷尼替丁在加速贮存条件下晶体缺陷导致亚硝胺生成。
IF 3.8 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2025-12-01 DOI: 10.1016/j.xphs.2025.103960
Jianchao Xu , Nicholas John Huls , Amber S. Jannasch , Eric J. Munson
The formation of nitrosamines, a class of potent carcinogen impurities, in pharmaceutical products such as ranitidine hydrochloride (RAN) has raised significant public health concerns and led to widespread product recalls. Previous studies have shown that RAN can degrade to N-nitrosodimethylamine (NDMA) after storage at 60 °C for several days. These studies also suggested a link between the degradation rate and the crystal morphology of the RAN. This study shows that NDMA formation in RAN is primarily driven by solid-state reactive species (SSRS) introduced during pharmaceutical manufacturing processes such as crystallization, milling, and grinding. Using cryogenic milling to introduce SSRS systematically, we assessed the stability of RAN at 60 °C and 0 % RH. Our results show a clear relationship between the amount of SSRS in RAN and the amount of NDMA formed upon stability, with cryoground samples exhibiting degradation rates up to two orders of magnitude higher than unprocessed samples. Furthermore, RAN tablets prepared with increased SSRS also showed accelerated NDMA formation. This study demonstrates the importance of mitigating SSRS in pharmaceutical manufacturing by mitigating the presence of SSRS in drug substances/products.
亚硝胺是一类强致癌物质的杂质,在盐酸雷尼替丁(RAN)等医药产品中形成亚硝胺引起了重大的公共卫生关注,并导致了广泛的产品召回。先前的研究表明,RAN在60℃下储存数天后可降解为n -亚硝基二甲胺(NDMA)。这些研究还表明,降解率与RAN的晶体形态之间存在联系。这项研究表明,在RAN中NDMA的形成主要是由结晶、研磨和研磨等制药制造过程中引入的固态反应物质(SSRS)驱动的。通过低温铣削系统地引入SSRS,我们评估了RAN在60 °C和0% RH下的稳定性。我们的研究结果表明,RAN中SSRS的数量与稳定性形成的NDMA的数量之间存在明确的关系,冷冻样品的降解率比未处理样品高两个数量级。此外,增加SSRS制备的RAN片也加速了NDMA的形成。本研究证明了通过减少原料药/制剂中SSRS的存在来减少SSRS在制药生产中的重要性。
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引用次数: 0
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Journal of pharmaceutical sciences
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