Journal of pharmaceutical sciences最新文献

英文中文

Impact of drug-polymer complexation and media properties on the release performance of amorphous solid dispersions containing a weakly basic drug and hydroxypropyl methylcellulose acetate succinate 药物-聚合物络合和介质性质对含有弱碱性药物和琥珀酸羟丙基甲基纤维素的非晶态固体分散体释放性能的影响。

IF 3.8 3区医学 Q2 CHEMISTRY, MEDICINAL

Journal of pharmaceutical sciences

Pub Date : 2025-12-01 DOI: 10.1016/j.xphs.2025.103894

Amanpreet Kaur , Dmitry Zemlyanov , Lynne S. Taylor

Herein, the release performance of amorphous solid dispersions (ASDs) of a weakly basic drug, bedaquiline (BDQ), and a weakly acidic polymer, hydroxypropyl methylcellulose acetate succinate (HPMCAS) was investigated in different media. In conjunction, the complexation tendency between BDQ and HPMCAS was also probed. Amorphous solid dispersions (ASDs) of BDQ were prepared at different drug loadings with LF and MF grades of HPMCAS using solvent evaporation. Drug-polymer complexation was investigated in buffers varying in pH from 5.8 to 10.5 and in biorelevant media. For these experiments, polymer concentration was quantified using colorimetry or high-performance liquid chromatography (HPLC) and evaporative light scattering detection (ELSD). The insoluble drug-polymer complex formed in some media was analyzed using attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy. Drug release from ASD powders was evaluated as a function of pH (1.6, 3.0, 5.0, 6.5) as well as in fasted and fed state simulated intestinal fluids. HPMCAS showed a high degree of insoluble complex formation (∼90 %) with BDQ at pH 6.0 and the extent of complexation decreased with increasing pH, or when biorelevant media was used. At pH 6.5, ASDs showed a low extent of release in buffer. Release of drug from the ASDs was considerably enhanced in biorelevant media. BDQ remained amorphous in the presence of HPMCAS for extended time periods, hence crystallization was not considered a failure mechanism. Instead, the low release extent observed in pH 6.5 buffer was attributed to the formation of an insoluble BDQ:polymer ionic complex in the ASD particle. Ionic complexation was confirmed using X-ray photoelectron spectroscopy. However, it appears that solubilizing species present in the biorelevant media disrupted the drug-polymer complexation leading to improved release. These studies highlight the convoluted nature of drug release from ASDs with enteric polymers and the need to consider the impact of the release testing conditions. Release as a function of media conditions, is in turn expected to be highly variable from drug to drug depending on the nature of the drug-polymer interactions.

本文研究了弱碱性药物贝达喹啉（BDQ）和弱酸性聚合物羟丙基甲基纤维素乙酸琥珀酸酯（HPMCAS）在不同介质中的释放性能。同时，探讨了BDQ与HPMCAS的络合趋势。采用溶剂蒸发法制备了不同载药量的BDQ非晶态固体分散体（ASDs）。在pH从5.8到10.5的缓冲液和生物相关介质中研究了药物-聚合物络合。在这些实验中，使用比色法或高效液相色谱法和蒸发光散射检测来定量聚合物浓度。采用衰减全反射-傅里叶变换红外（ATR-FTIR）光谱分析了在某些介质中形成的不溶性药物-聚合物配合物。通过pH值（1.6、3.0、5.0、6.5）以及空腹和进食状态模拟肠液，评估ASD粉末的药物释放情况。HPMCAS在pH 6.0时与BDQ形成高度不溶性络合物（约90%），并且络合程度随着pH的增加或使用生物相关培养基而降低。在pH 6.5时，ASDs在缓冲液中的释放程度较低。在生物相关介质中，asd的药物释放明显增强。BDQ在HPMCAS存在下长时间保持无定形，因此结晶不被认为是失效机制。相反，在pH 6.5缓冲液中观察到的低释放程度归因于ASD颗粒中不溶性BDQ：聚合物离子复合物的形成。用x射线光电子能谱证实了离子络合作用。然而，生物相关介质中存在的溶解性物质似乎破坏了药物-聚合物的络合，从而改善了释放。这些研究强调了肠道聚合物从asd中释放药物的复杂性质，以及考虑释放测试条件影响的必要性。释放作为介质条件的函数，根据药物-聚合物相互作用的性质，不同药物之间的释放预期是高度可变的。

{"title":"Impact of drug-polymer complexation and media properties on the release performance of amorphous solid dispersions containing a weakly basic drug and hydroxypropyl methylcellulose acetate succinate","authors":"Amanpreet Kaur , Dmitry Zemlyanov , Lynne S. Taylor","doi":"10.1016/j.xphs.2025.103894","DOIUrl":"10.1016/j.xphs.2025.103894","url":null,"abstract":"<div><div>Herein, the release performance of amorphous solid dispersions (ASDs) of a weakly basic drug, bedaquiline (BDQ), and a weakly acidic polymer, hydroxypropyl methylcellulose acetate succinate (HPMCAS) was investigated in different media. In conjunction, the complexation tendency between BDQ and HPMCAS was also probed. Amorphous solid dispersions (ASDs) of BDQ were prepared at different drug loadings with LF and MF grades of HPMCAS using solvent evaporation. Drug-polymer complexation was investigated in buffers varying in pH from 5.8 to 10.5 and in biorelevant media. For these experiments, polymer concentration was quantified using colorimetry or high-performance liquid chromatography (HPLC) and evaporative light scattering detection (ELSD). The insoluble drug-polymer complex formed in some media was analyzed using attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy. Drug release from ASD powders was evaluated as a function of pH (1.6, 3.0, 5.0, 6.5) as well as in fasted and fed state simulated intestinal fluids. HPMCAS showed a high degree of insoluble complex formation (∼90 %) with BDQ at pH 6.0 and the extent of complexation decreased with increasing pH, or when biorelevant media was used. At pH 6.5, ASDs showed a low extent of release in buffer. Release of drug from the ASDs was considerably enhanced in biorelevant media. BDQ remained amorphous in the presence of HPMCAS for extended time periods, hence crystallization was not considered a failure mechanism. Instead, the low release extent observed in pH 6.5 buffer was attributed to the formation of an insoluble BDQ:polymer ionic complex in the ASD particle. Ionic complexation was confirmed using X-ray photoelectron spectroscopy. However, it appears that solubilizing species present in the biorelevant media disrupted the drug-polymer complexation leading to improved release. These studies highlight the convoluted nature of drug release from ASDs with enteric polymers and the need to consider the impact of the release testing conditions. Release as a function of media conditions, is in turn expected to be highly variable from drug to drug depending on the nature of the drug-polymer interactions.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 12","pages":"Article 103894"},"PeriodicalIF":3.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591511","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

Corrigendum to “Three-Dimensional Printing in Pharmaceutics: Promises and Problems” [Journal of Pharmaceutical Sciences, Volume 97, Issue 9, September 2008, Pages 3666-3690] “制药中的三维打印：承诺和问题”的勘误表。

IF 3.8 3区医学 Q2 CHEMISTRY, MEDICINAL

Journal of pharmaceutical sciences

Pub Date : 2025-12-01 DOI: 10.1016/j.xphs.2025.103883

Deng Guang Yu , Li-Min Zhu , Christopher J. Branford-White , Xiang Liang Yang

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 3.8 3区医学 Q2 CHEMISTRY, MEDICINAL

Journal of pharmaceutical sciences

Pub Date : 2025-12-01 DOI: 10.1016/j.xphs.2025.103808

Kinam Park

引用次数: 0

Penetration depth and effective sample size characterization of UV/Vis radiation into pharmaceutical tablets 紫外/可见辐射在片剂中的渗透深度和有效样品尺寸表征。

IF 3.8 3区医学 Q2 CHEMISTRY, MEDICINAL

Journal of pharmaceutical sciences

Pub Date : 2025-12-01 DOI: 10.1016/j.xphs.2025.103889

René Brands , Lukas Fuchs , Judith M. Seyffer , Naim Bajcinca , Jens Bartsch , Urs A. Peuker , Volker Schmidt , Markus Thommes

The pharmaceutical industry is moving from off-line to real-time release testing (RTRT) to enhance quality while reducing costs. UV/Vis spectroscopy has emerged as a promising tool for RTRT given its simplicity, sensitivity and cost-effectiveness. Nevertheless, the effective sample size must be characterized in relation to the penetration depth to justify its representativeness and suitability for RTRT. In this study, bilayer tablets were produced using a hydraulic tablet press. The lower layer contained titanium dioxide and microcrystalline cellulose (MCC), while the upper layer consisted of MCC, lactose or a combination with theophylline. The thickness of the upper layer was stepwise increased. Spectra from 224 to 820 nm were recorded with an orthogonally aligned UV/Vis probe. Thereby, the experimental penetration depth reached up to 0.4 mm, while the Kubelka-Munk model yielded a theoretical maximum penetration depth of 1.38 mm. Based on these values, the effective sample sizes were determined. Considering a parabolic penetration profile, the maximum volume was 2.01 mm³. The results indicated a wavelength and particle size dependency. Micro-CT analysis confirmed the even distribution of the API in the tablets proving the sufficiency of the UV/Vis sample size. Consequently, UV/Vis spectroscopy is a reliable alternative for RTRT in tableting.

制药行业正在从离线转向实时释放测试（RTRT），以提高质量，同时降低成本。由于其简单、敏感和成本效益，紫外/可见光谱学已成为RTRT的一种有前途的工具。然而，有效样本量必须与渗透深度相关，以证明其代表性和RTRT的适用性。本研究采用液压机生产双层片剂。下层含有二氧化钛和微晶纤维素（MCC），上层由MCC、乳糖或与茶碱的组合组成。上层厚度逐步增加。用正交排列的紫外/可见探针记录了224 ~ 820 nm的光谱。因此，实验侵彻深度可达0.4 mm，而Kubelka-Munk模型的理论最大侵彻深度为1.38 mm。根据这些值，确定有效样本量。考虑抛物线侵彻剖面，最大体积为2.01 mm³。结果表明波长和颗粒大小相关。显微ct分析证实了原料药在片剂中的均匀分布，证明了紫外/可见样本量的充分性。因此，紫外/可见光谱法是RTRT压片的可靠替代方法。

{"title":"Penetration depth and effective sample size characterization of UV/Vis radiation into pharmaceutical tablets","authors":"René Brands , Lukas Fuchs , Judith M. Seyffer , Naim Bajcinca , Jens Bartsch , Urs A. Peuker , Volker Schmidt , Markus Thommes","doi":"10.1016/j.xphs.2025.103889","DOIUrl":"10.1016/j.xphs.2025.103889","url":null,"abstract":"<div><div>The pharmaceutical industry is moving from off-line to real-time release testing (RTRT) to enhance quality while reducing costs. UV/Vis spectroscopy has emerged as a promising tool for RTRT given its simplicity, sensitivity and cost-effectiveness. Nevertheless, the effective sample size must be characterized in relation to the penetration depth to justify its representativeness and suitability for RTRT. In this study, bilayer tablets were produced using a hydraulic tablet press. The lower layer contained titanium dioxide and microcrystalline cellulose (MCC), while the upper layer consisted of MCC, lactose or a combination with theophylline. The thickness of the upper layer was stepwise increased. Spectra from 224 to 820 nm were recorded with an orthogonally aligned UV/Vis probe. Thereby, the experimental penetration depth reached up to 0.4 mm, while the Kubelka-Munk model yielded a theoretical maximum penetration depth of 1.38 mm. Based on these values, the effective sample sizes were determined. Considering a parabolic penetration profile, the maximum volume was 2.01 mm³. The results indicated a wavelength and particle size dependency. Micro-CT analysis confirmed the even distribution of the API in the tablets proving the sufficiency of the UV/Vis sample size. Consequently, UV/Vis spectroscopy is a reliable alternative for RTRT in tableting.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 12","pages":"Article 103889"},"PeriodicalIF":3.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512066","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

In memory of Professor William I. Higuchi (1931–2024) 纪念通口威廉教授（1931-2024）。

IF 3.8 3区医学 Q2 CHEMISTRY, MEDICINAL

Journal of pharmaceutical sciences

Pub Date : 2025-12-01 DOI: 10.1016/j.xphs.2025.103926

Bradley D. Anderson , Daniel J.A. Crommelin , James N. Herron

引用次数: 0

Temperature-dependent colloidal behavior of polymer-stabilized gold nanoparticles 聚合物稳定金纳米颗粒的温度依赖性胶体行为。

IF 3.8 3区医学 Q2 CHEMISTRY, MEDICINAL

Journal of pharmaceutical sciences

Pub Date : 2025-12-01 DOI: 10.1016/j.xphs.2025.104060

Amit K. Barui , Tori Leyba , Rachel Edwards , Lia A. Stanciu

Polymer-based composites, like polystyrene-gold nanoparticles (PS-AuNPs) are widely used in pharmaceutical and biomedical applications including targeted drug delivery, imaging, biosensing, and photothermal due to their combined plasmonic and structural properties. However, processing conditions significantly influence their structural and functional properties. This study investigates the effects of synthesis temperature on the stability and resuspension behavior of PS-AuNPs, focusing on a range of 78–90 °C. At temperatures below 84 °C, PS-AuNPs maintain stability, forming well-defined pellets after centrifugation and resuspending efficiently. At 86 °C, a coating over the gold nanoparticles was observed via transmission electron microscopy (TEM), which was attributed to the partial softening of polystyrene because of approaching its glass transition temperature regime of around 90 °C. This structural degradation reduced the resuspension efficiency and increased aggregation in high ionic strength environments. Salt aggregation tests showed significant nanoparticle instability at higher synthesis temperatures, as shown by the visible aggregation and sedimentation of the particles in the presence of NaCl.

聚合物基复合材料，如聚苯乙烯-金纳米颗粒（PS-AuNPs），由于其结合的等离子体和结构特性，广泛应用于制药和生物医学应用，包括靶向药物输送、成像、生物传感和光热。然而，加工条件对其结构和功能性能有显著影响。本研究研究了合成温度对PS-AuNPs稳定性和再悬浮行为的影响，重点研究了合成温度在78-90°C的范围内。在低于84°C的温度下，PS-AuNPs保持稳定性，在离心和重悬后形成明确的颗粒。在86°C时，通过透射电子显微镜（TEM）观察到金纳米颗粒上有一层涂层，这是由于聚苯乙烯的部分软化，因为它接近90°C左右的玻璃化转变温度。这种结构降解降低了再悬浮效率，增加了高离子强度环境中的聚集。盐聚集试验表明，在较高的合成温度下，纳米颗粒具有明显的不稳定性，如在NaCl存在下粒子的聚集和沉降所示。

{"title":"Temperature-dependent colloidal behavior of polymer-stabilized gold nanoparticles","authors":"Amit K. Barui , Tori Leyba , Rachel Edwards , Lia A. Stanciu","doi":"10.1016/j.xphs.2025.104060","DOIUrl":"10.1016/j.xphs.2025.104060","url":null,"abstract":"<div><div>Polymer-based composites, like polystyrene-gold nanoparticles (PS-AuNPs) are widely used in pharmaceutical and biomedical applications including targeted drug delivery, imaging, biosensing, and photothermal due to their combined plasmonic and structural properties. However, processing conditions significantly influence their structural and functional properties. This study investigates the effects of synthesis temperature on the stability and resuspension behavior of PS-AuNPs, focusing on a range of 78–90 °C. At temperatures below 84 °C, PS-AuNPs maintain stability, forming well-defined pellets after centrifugation and resuspending efficiently. At 86 °C, a coating over the gold nanoparticles was observed via transmission electron microscopy (TEM), which was attributed to the partial softening of polystyrene because of approaching its glass transition temperature regime of around 90 °C. This structural degradation reduced the resuspension efficiency and increased aggregation in high ionic strength environments. Salt aggregation tests showed significant nanoparticle instability at higher synthesis temperatures, as shown by the visible aggregation and sedimentation of the particles in the presence of NaCl.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 12","pages":"Article 104060"},"PeriodicalIF":3.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145834186","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

Pediatric off-label use and nonadherence management for nadolol: A mechanistic PBPK model incorporating ontogeny scaling from interracial adults to children 纳多洛尔的儿科超说明书使用和不依从性管理：一个包含跨种族成人到儿童个体发育尺度的PBPK机制模型。

IF 3.8 3区医学 Q2 CHEMISTRY, MEDICINAL

Journal of pharmaceutical sciences

Pub Date : 2025-12-01 DOI: 10.1016/j.xphs.2025.103707

Xiang Chen , Guo Yu , Guangji Wang , Guo-Fu Li

Nadolol has demonstrated its superior efficacy over other β-blockers in the treatment of specific cardiovascular diseases in children. The clinical development of nadolol for pediatric use was prioritized by Chinese healthcare authorities in May 2023 while there was a lack of clear medication instructions for children. To expedite the pediatric development of nadolol and provide insights into its off-label applications, we developed a physiologically based pharmacokinetic model incorporating mechanistic disposition knowledge. This model integrates key processes of nadolol including P-glycoprotein (P-gp) transporter mediated the absorption of efflux, multidrug and toxin extrusion protein (MATE) 1 transporter and organic cation (OCT) 2 transporter mediated active renal excretion, organic anion transporting polypeptide (OATP) 1A2 mediated transport, along with biliary excretion. The model accurately captured the pharmacokinetic profiles of nadolol in both Western and East Asian populations following a wide dose range (2–160 mg), including the plasma concentration, urine excretion, and drug-drug interactions with the P-gp inhibitor. After our good validation on interracial adult populations, simulations of nadolol pharmacokinetic profiles in the Chinese population were performed by adjusting the liver volume of the Chinese to 0.9 of the Japanese population. Then, with the consideration of physiological changes and plasma protein ontogeny in pediatrics, the nadolol model for pediatrics was also well-verified on several children aged 3 months to 121 months. Accordingly, specific optimal dosages for children across various ages and racial backgrounds with or without obesity were offered by exposure matching with adults. Multiple remedial regimen simulations were also compared to obtain the best nonadherence management in the case of missed dosages, in which resuming a regular dose as soon as possible was the most recommended.

纳多洛尔在治疗儿童特定心血管疾病方面已证明其优于其他β受体阻滞剂的疗效。在缺乏明确的儿童用药说明的情况下，中国卫生主管部门于2023年5月优先考虑了纳多洛尔的临床开发。为了加快纳多洛尔的儿科开发，并深入了解其标签外应用，我们开发了一个基于生理学的药代动力学模型，并结合了机制处置知识。该模型整合了纳多洛尔的关键过程，包括p -糖蛋白（P-gp）转运体介导的外排吸收、多药物和毒素挤出蛋白（MATE） 1转运体和有机阳离子（OCT） 2转运体介导的主动肾排泄、有机阴离子转运多肽（OATP） 1A2介导的转运以及胆道排泄。该模型准确地捕获了纳多洛尔在西方和东亚人群中较宽剂量范围（2-160 mg）的药代动力学特征，包括血浆浓度、尿排泄以及与P-gp抑制剂的药物-药物相互作用。在我们对不同种族的成人人群进行了良好的验证后，通过将中国人的肝脏体积调整为日本人的0.9，模拟了纳多洛尔在中国人群中的药代动力学特征。然后，考虑到儿科生理变化和血浆蛋白的个体发生，儿科纳多洛尔模型也在几个3 ~ 121月龄的儿童身上得到了很好的验证。因此，通过与成人的暴露匹配，为不同年龄和种族背景的儿童提供了特定的最佳剂量，无论是否肥胖。多种治疗方案模拟也进行了比较，以获得在错过剂量的情况下的最佳不依从管理，其中最建议尽快恢复常规剂量。

{"title":"Pediatric off-label use and nonadherence management for nadolol: A mechanistic PBPK model incorporating ontogeny scaling from interracial adults to children","authors":"Xiang Chen , Guo Yu , Guangji Wang , Guo-Fu Li","doi":"10.1016/j.xphs.2025.103707","DOIUrl":"10.1016/j.xphs.2025.103707","url":null,"abstract":"<div><div>Nadolol has demonstrated its superior efficacy over other β-blockers in the treatment of specific cardiovascular diseases in children. The clinical development of nadolol for pediatric use was prioritized by Chinese healthcare authorities in May 2023 while there was a lack of clear medication instructions for children. To expedite the pediatric development of nadolol and provide insights into its off-label applications, we developed a physiologically based pharmacokinetic model incorporating mechanistic disposition knowledge. This model integrates key processes of nadolol including P-glycoprotein (P-gp) transporter mediated the absorption of efflux, multidrug and toxin extrusion protein (MATE) 1 transporter and organic cation (OCT) 2 transporter mediated active renal excretion, organic anion transporting polypeptide (OATP) 1A2 mediated transport, along with biliary excretion. The model accurately captured the pharmacokinetic profiles of nadolol in both Western and East Asian populations following a wide dose range (2–160 mg), including the plasma concentration, urine excretion, and drug-drug interactions with the P-gp inhibitor. After our good validation on interracial adult populations, simulations of nadolol pharmacokinetic profiles in the Chinese population were performed by adjusting the liver volume of the Chinese to 0.9 of the Japanese population. Then, with the consideration of physiological changes and plasma protein ontogeny in pediatrics, the nadolol model for pediatrics was also well-verified on several children aged 3 months to 121 months. Accordingly, specific optimal dosages for children across various ages and racial backgrounds with or without obesity were offered by exposure matching with adults. Multiple remedial regimen simulations were also compared to obtain the best nonadherence management in the case of missed dosages, in which resuming a regular dose as soon as possible was the most recommended.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 12","pages":"Article 103707"},"PeriodicalIF":3.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515869","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 self-assembled nanocomplex from starch-protein- fatty acid: Thermodynamics of self-assembly 淀粉-蛋白质-脂肪酸自组装纳米复合物：自组装热力学。

IF 3.8 3区医学 Q2 CHEMISTRY, MEDICINAL

Journal of pharmaceutical sciences

Pub Date : 2025-12-01 DOI: 10.1016/j.xphs.2025.104018

Deepak Bhopatkar , Bruce R. Hamaker , Nawel Khalef , Aziz Bakri , Osvaldo H. Campanella

A self-assembling, nanoscale complex formed from common biological molecules, starch, proteins, and fatty acids, was previously reported by our group. While the formation of this nanocomplex has been confirmed using various analytical techniques, its thermodynamic distinctiveness compared to conventional nano-emulsion systems has not yet been explored. This study aims to provide a physicochemical understanding of the self-assembly process by evaluating changes in thermodynamic properties, enthalpy, entropy, and the Gibbs free energy during complex formation. Interactions among these biological molecules, mixed in specific ratios, were monitored using modulated differential scanning calorimetry (MDSC). Changes in the reversing heat capacity during the initial cooling cycle were used to calculate the entropic and the Gibbs free energy changes associated with self-assembly. Applying classical equilibrium thermodynamics, it was demonstrated that the presence of protein thermodynamically favored the formation of a higher-order nanostructure, distinguishing it from typical emulsion systems. Moreover, this structure is more stable than binary complexes such as amylose–fatty acid and protein–fatty acid assemblies. Our findings provide compelling evidence that these self-assembling nanoscale complexes are not only chemically viable but also thermodynamically favored and stable.

我们小组之前报道了一种自组装的纳米级复合物，它由常见的生物分子、淀粉、蛋白质和脂肪酸组成。虽然这种纳米复合物的形成已经通过各种分析技术得到证实，但与传统纳米乳液体系相比，其热力学特性尚未得到探讨。本研究旨在通过评估复合物形成过程中热力学性质、焓、熵和吉布斯自由能的变化，提供自组装过程的物理化学理解。这些生物分子之间的相互作用，混合在特定的比例，监测使用调制差示扫描量热法（MDSC）。利用初始冷却循环中可逆热容的变化来计算自组装过程中的熵和吉布斯自由能变化。应用经典平衡热力学，证明了蛋白质的存在有利于形成高阶纳米结构，使其与典型的乳状体系区别。此外，这种结构比二元配合物更稳定，如直链淀粉-脂肪酸和蛋白质-脂肪酸组合。我们的发现提供了令人信服的证据，证明这些自组装的纳米级复合物不仅在化学上可行，而且在热力学上有利和稳定。

{"title":"A self-assembled nanocomplex from starch-protein- fatty acid: Thermodynamics of self-assembly","authors":"Deepak Bhopatkar , Bruce R. Hamaker , Nawel Khalef , Aziz Bakri , Osvaldo H. Campanella","doi":"10.1016/j.xphs.2025.104018","DOIUrl":"10.1016/j.xphs.2025.104018","url":null,"abstract":"<div><div>A self-assembling, nanoscale complex formed from common biological molecules, starch, proteins, and fatty acids, was previously reported by our group. While the formation of this nanocomplex has been confirmed using various analytical techniques, its thermodynamic distinctiveness compared to conventional nano-emulsion systems has not yet been explored. This study aims to provide a physicochemical understanding of the self-assembly process by evaluating changes in thermodynamic properties, enthalpy, entropy, and the Gibbs free energy during complex formation. Interactions among these biological molecules, mixed in specific ratios, were monitored using modulated differential scanning calorimetry (MDSC). Changes in the reversing heat capacity during the initial cooling cycle were used to calculate the entropic and the Gibbs free energy changes associated with self-assembly. Applying classical equilibrium thermodynamics, it was demonstrated that the presence of protein thermodynamically favored the formation of a higher-order nanostructure, distinguishing it from typical emulsion systems. Moreover, this structure is more stable than binary complexes such as amylose–fatty acid and protein–fatty acid assemblies. Our findings provide compelling evidence that these self-assembling nanoscale complexes are not only chemically viable but also thermodynamically favored and stable.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 12","pages":"Article 104018"},"PeriodicalIF":3.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275073","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

Investigating the effect of solvent polarity environment differences in electrolyte and non-electrolyte systems 研究了电解质和非电解质体系中溶剂极性环境差异的影响。

IF 3.8 3区医学 Q2 CHEMISTRY, MEDICINAL

Journal of pharmaceutical sciences

Pub Date : 2025-12-01 DOI: 10.1016/j.xphs.2025.104044

Valeria Briceida Tellez-Gallego, Kate Sorg, Rodolfo Pinal

To address the knowledge gap regarding the polarity of excipient solutions and the impact on biologically relevant systems, a comprehensive exploration of the polarity of solutions is essential. This study explores the solvatochromic response of Reichardt’s dye to solvent polarity in aqueous solutions, focusing on structurally similar electrolytes and non-electrolytes at concentrations typically used in pharmaceutical formulations. UV absorbance measurements demonstrated sensitivity to subtle structural differences, such as counterion variations or glycosidic bonds. Here, chloride salts and disaccharides were analyzed and notable polarity differences between similar systems were found. Additionally, unexpected similarities between sodium chloride and trehalose were observed. This investigation underscores the potential of readily accessible solvent polarity and solvatochromic studies to deepen the understanding of aqueous solutions and extend their application to pharmaceutical excipients and their roles in protein formulation.

为了解决关于赋形剂溶液极性和对生物相关系统的影响的知识差距，对溶液极性的全面探索是必不可少的。本研究探讨了Reichardt染料在水溶液中对溶剂极性的溶剂变色反应，重点关注结构相似的电解质和药物配方中通常使用浓度的非电解质。紫外吸收测量显示了对细微结构差异的敏感性，如反离子变化或糖苷键。本文对氯盐和双糖进行了分析，发现相似体系之间存在显著的极性差异。此外，观察到氯化钠和海藻糖之间意想不到的相似性。这项研究强调了易于获得的溶剂极性和溶剂致变色研究的潜力，以加深对水溶液的理解，并将其应用于药用辅料及其在蛋白质配方中的作用。

引用次数: 0

An integrated material-sparing method for determining dilution potential of direct compression tablet fillers 一种测定直接压缩片剂稀释势的综合省料方法。

IF 3.8 3区医学 Q2 CHEMISTRY, MEDICINAL

Journal of pharmaceutical sciences

Pub Date : 2025-12-01 DOI: 10.1016/j.xphs.2025.104061

Weeraya Tharanon , Yiwang Guo , Jomjai Peerapattana , Changquan Calvin Sun

An ideal filler for direct compression (DC) formulation requires both good flowability and compactibility. To ensure consistent tablet quality across various APIs and API loadings, as well as successful manufacturability, it is essential to understand the “dilution potential” of any DC tablet filler. In this study, an integrated material-sparing laboratory-scale method was developed to evaluate the dilution potential of a co-processed glutinous rice starch (CP-GRS) using two grades of acetaminophen (APAP) and ibuprofen (IBN) as model drugs. This method considers three criteria pertaining to tablet performance and manufacturability: (1) <1 % weight loss for the friability, (2) a disintegration time (DT) of <15 min, and (3) superior flowability compared to microcrystalline cellulose (Avicel® PH102). The maximum drug loading at the appropriate critical pressure (P_c) was determined, indicating the dilution potential. The results showed that granular APAP (gAPAP) could be loaded up to 34 % in CP-GRS at a compaction pressure of ∼240 MPa, fine APAP achieved a loading of 20 % in the range of 143–288 MPa, and IBN reached a maximum API loading of 40 % within the 115–150 MPa range. This integrated method, by minimizing material consumption, can also be applied to enable efficient DC formulation development of an API of interest during an early drug development phase.

直接压缩（DC）配方的理想填料要求具有良好的流动性和致密性。为了确保不同API和API负载的片剂质量一致，以及成功的可制造性，了解任何直流片剂填料的“稀释潜力”至关重要。本研究以对乙酰氨基酚（APAP）和布洛芬（IBN）为模型药物，建立了一种节省材料的综合实验室规模方法来评估共加工糯米淀粉（CP-GRS）的稀释潜力。该方法考虑了与片剂性能和可生产性有关的三个标准：(1)c)已确定，表明稀释潜力。结果表明，颗粒状APAP （gAPAP）在约240 MPa的压实压力下可在CP-GRS中加载34%，细粒APAP在143 ~ 288 MPa范围内加载20%，IBN在115 ~ 150 MPa范围内最大加载40%。这种集成的方法，通过减少材料消耗，也可以应用于在药物开发的早期阶段有效地开发感兴趣的原料药的直流配方。

{"title":"An integrated material-sparing method for determining dilution potential of direct compression tablet fillers","authors":"Weeraya Tharanon , Yiwang Guo , Jomjai Peerapattana , Changquan Calvin Sun","doi":"10.1016/j.xphs.2025.104061","DOIUrl":"10.1016/j.xphs.2025.104061","url":null,"abstract":"<div><div>An ideal filler for direct compression (DC) formulation requires both good flowability and compactibility. To ensure consistent tablet quality across various APIs and API loadings, as well as successful manufacturability, it is essential to understand the “dilution potential” of any DC tablet filler. In this study, an integrated material-sparing laboratory-scale method was developed to evaluate the dilution potential of a co-processed glutinous rice starch (CP-GRS) using two grades of acetaminophen (APAP) and ibuprofen (IBN) as model drugs. This method considers three criteria pertaining to tablet performance and manufacturability: (1) <1 % weight loss for the friability, (2) a disintegration time (DT) of <15 min, and (3) superior flowability compared to microcrystalline cellulose (Avicel® PH102). The maximum drug loading at the appropriate critical pressure (<em>P</em><sub>c</sub>) was determined, indicating the dilution potential. The results showed that granular APAP (gAPAP) could be loaded up to 34 % in CP-GRS at a compaction pressure of ∼240 MPa, fine APAP achieved a loading of 20 % in the range of 143–288 MPa, and IBN reached a maximum API loading of 40 % within the 115–150 MPa range. This integrated method, by minimizing material consumption, can also be applied to enable efficient DC formulation development of an API of interest during an early drug development phase.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 12","pages":"Article 104061"},"PeriodicalIF":3.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145834108","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

首页上一页

下一页尾页

类型

全部化学•材料生命科学医学物理工程技术环境•农林材料科学地球科学法学管理学化学环境科学与生态学计算机科学教育学经济学农林科学人文科学生物学数学物理与天体物理心理学综合性期刊其他工业工程理学历史学农学文学信息工程

数据库

全部 ACS Publications Elsevier ieeexplore Springer The Royal Society of Chemistry Wiley

期刊

Journal of pharmaceutical sciences

全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.

﹀