首页 > 最新文献

Journal of pharmaceutical sciences最新文献

英文 中文
Oral viscous budesonide solution for enhanced localized treatment of eosinophilic esophagitis through improved mucoadhesion and permeation. 粘稠布地奈德口服溶液通过改善粘附性和渗透性加强对嗜酸性粒细胞食管炎的局部治疗
IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-09-24 DOI: 10.1016/j.xphs.2024.09.016
Dongyu Wu, Tiantian Zhang, Yuzhen Kang, Yan Zhong, Shiqi Chen, Yue Zhang, Xuyu Chai

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus that is immune/antigen-mediated and often requires targeted treatment. In clinical practice, an oral viscous budesonide suspension prepared by adding sucralose to a budesonide suspension for inhalation (Pulmicort®) is used to treat adult EoE and enhance retention in the esophageal mucosa. Inspired by this off-label drug use, oral viscous budesonide solutions (OVBSs) were developed in this study, and their capacities for adhesion, permeation, and stability were explored. Given the insolubility of budesonide as a BCS II drug, we first evaluated its equilibrium solubility and found that Transcutol® HP was an excellent choice for creating an OVBS at a concentration of 0.2 mg/g. The rheological properties of the OVBSs were evaluated with a rheometer, and shear-thinning, which aids in swallowing, was observed. The addition of hydroxyethyl cellulose (HEC) increased the adhesion strength of the preparation, which was associated with the hydration and thickening mechanism. This result was confirmed in a dynamic gelation study and in vitro elution experiment conducted with porcine esophagus tissue. Furthermore, the permeabilities of the OVBSs in the porcine esophagus were evaluated with a Franz diffusion cell device. >80 % of the budesonide was released after 24 h, and the release profile was similar to that of the solution. To explore the storage conditions of OVBSs, critical factors such as pH, content, and impurities were determined. It was found that OVBSs exhibited different behaviors at different pH values and temperatures. Notably, the OVBSs containing 1.7 % HEC could be stored for >6 months at a temperature of 5 °C ± 3 °C and a pH of 4.5 without significant degradation. Overall, this study demonstrated that OVBSs have the potential to adhere to the esophageal mucosa, permeate the tissue, and remain stable during storage. Moreover, OVBSs exhibit a distinct advantage over traditional converted inhalation-to-oral budesonide therapies by enabling flexible dose adjustment in clinical applications, thereby potentially minimizing systemic side effects commonly associated with oral glucocorticoid administration.

嗜酸性粒细胞食管炎(EoE)是一种食管慢性炎症性疾病,由免疫/抗原介导,通常需要针对性治疗。在临床实践中,一种通过在吸入用布地奈德混悬液(Pulmicort®)中添加蔗糖而制备的粘稠布地奈德口服混悬液被用于治疗成人食管炎,并增强其在食管粘膜中的滞留。受这种标签外用药的启发,本研究开发了口服粘稠布地奈德溶液(OVBSs),并探索了其粘附、渗透和稳定性能力。鉴于布地奈德作为一种 BCS II 药物具有不溶性,我们首先对其平衡溶解度进行了评估,发现 Transcutol® HP 是配制浓度为 0.2 mg/g 的 OVBS 的最佳选择。我们使用流变仪对 OVBS 的流变特性进行了评估,观察到了有助于吞咽的剪切稀化现象。羟乙基纤维素(HEC)的加入增加了制剂的粘附强度,这与水合和增稠机制有关。用猪食道组织进行的动态凝胶研究和体外洗脱实验证实了这一结果。此外,还利用弗朗兹扩散池装置评估了 OVBS 在猪食道中的渗透性。24 小时后,超过 80% 的布地奈德被释放出来,释放曲线与溶液相似。为了探索 OVBS 的储存条件,研究人员测定了 pH 值、含量和杂质等关键因素。结果发现,OVBS 在不同的 pH 值和温度下表现出不同的行为。值得注意的是,含有 1.7% HEC 的 OVBS 在温度为 5°C ± 3°C 和 pH 值为 4.5 的条件下可储存 6 个月以上,且无明显降解。总之,这项研究表明,OVBSs 具有粘附食管粘膜、渗透组织并在储存期间保持稳定的潜力。此外,与传统的吸入-口服布地奈德转换疗法相比,OVBSs 具有明显的优势,在临床应用中可以灵活调整剂量,从而有可能最大限度地减少口服糖皮质激素常见的全身副作用。
{"title":"Oral viscous budesonide solution for enhanced localized treatment of eosinophilic esophagitis through improved mucoadhesion and permeation.","authors":"Dongyu Wu, Tiantian Zhang, Yuzhen Kang, Yan Zhong, Shiqi Chen, Yue Zhang, Xuyu Chai","doi":"10.1016/j.xphs.2024.09.016","DOIUrl":"10.1016/j.xphs.2024.09.016","url":null,"abstract":"<p><p>Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus that is immune/antigen-mediated and often requires targeted treatment. In clinical practice, an oral viscous budesonide suspension prepared by adding sucralose to a budesonide suspension for inhalation (Pulmicort®) is used to treat adult EoE and enhance retention in the esophageal mucosa. Inspired by this off-label drug use, oral viscous budesonide solutions (OVBSs) were developed in this study, and their capacities for adhesion, permeation, and stability were explored. Given the insolubility of budesonide as a BCS II drug, we first evaluated its equilibrium solubility and found that Transcutol® HP was an excellent choice for creating an OVBS at a concentration of 0.2 mg/g. The rheological properties of the OVBSs were evaluated with a rheometer, and shear-thinning, which aids in swallowing, was observed. The addition of hydroxyethyl cellulose (HEC) increased the adhesion strength of the preparation, which was associated with the hydration and thickening mechanism. This result was confirmed in a dynamic gelation study and in vitro elution experiment conducted with porcine esophagus tissue. Furthermore, the permeabilities of the OVBSs in the porcine esophagus were evaluated with a Franz diffusion cell device. >80 % of the budesonide was released after 24 h, and the release profile was similar to that of the solution. To explore the storage conditions of OVBSs, critical factors such as pH, content, and impurities were determined. It was found that OVBSs exhibited different behaviors at different pH values and temperatures. Notably, the OVBSs containing 1.7 % HEC could be stored for >6 months at a temperature of 5 °C ± 3 °C and a pH of 4.5 without significant degradation. Overall, this study demonstrated that OVBSs have the potential to adhere to the esophageal mucosa, permeate the tissue, and remain stable during storage. Moreover, OVBSs exhibit a distinct advantage over traditional converted inhalation-to-oral budesonide therapies by enabling flexible dose adjustment in clinical applications, thereby potentially minimizing systemic side effects commonly associated with oral glucocorticoid administration.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348860","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
Determination of Solid-State Acidity of Lyophilized Trehalose Containing Citrate, Phosphate, and Histidine Buffers Using UV/VIS Diffuse Reflectance and Solid-State NMR Spectroscopy. 利用 UV/VIS 漫反射和固态 NMR 光谱测定含柠檬酸盐、磷酸盐和组氨酸缓冲液的冻干海藻糖的固态酸度。
IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-09-21 DOI: 10.1016/j.xphs.2024.09.019
Ashley Lay-Fortenbery, Xiaoda Yuan, Lukáš Veselý, Dominik Heger, Evgenyi Shalaev, Yongchao Su, Eric Munson

Changes in the protonation state of lyophilized proteins can impact structural integrity, chemical stability, and propensity to aggregate upon reconstitution. When a buffer is chosen, the freezing/drying process may result in dramatic changes in the protonation state of the protein due to ionization shift of the buffer. In order to determine whether protonation shifts are occurring, ionizable probes can be added to the formulation. Optical probes (dyes) have shown dramatic ionization changes in lyophilized products, but it is unclear whether the pH indicator is uniform throughout the matrix and whether the change in the pH indicator actually mirrors drug ionization changes. In solid-state NMR (SSNMR) spectroscopy, the chemical shift of the carbonyl carbon in carboxylic acids is very sensitive to the ionization state of the acid. Therefore, SSNMR can be used to measure ionization changes in a lyophilized matrix by employing a small quantity of an isotopically-labeled carboxylic acid species in the formulation. This paper compares the apparent pH of six trehalose-containing lyophilized buffer systems using SSNMR and UV-Vis diffuse reflectance spectroscopy (UVDRS). Both SSNMR and UVDRS results using two different ionization probes (butyric acid and bromocresol purple, respectively) showed little change in apparent acidity compared to the pre-lyophilized solution in a sodium citrate buffer, but a greater change was observed in potassium phosphate, sodium phosphate, and histidine buffers. While the trends between the two methods were similar, there were differences in the numerical values of equivalent pH (pHeq) observed between the two methods. The potential causes contributing to the differences are discussed.

冻干蛋白质质子化状态的变化会影响结构的完整性、化学稳定性以及重组时的聚集倾向。在选择缓冲液时,冷冻/干燥过程可能会因缓冲液的电离偏移而导致蛋白质质子状态的剧烈变化。为了确定是否发生了质子转变,可在制剂中加入可电离的探针。光学探针(染料)在冻干产品中显示出显著的电离变化,但目前还不清楚 pH 指示剂在整个基质中是否均匀,也不清楚 pH 指示剂的变化是否实际反映了药物的电离变化。在固态核磁共振(SSNMR)光谱中,羧酸中羰基碳的化学位移对酸的电离状态非常敏感。因此,通过在制剂中使用少量同位素标记的羧酸种类,SSNMR 可用来测量冻干基质中的电离变化。本文使用 SSNMR 和紫外可见光漫反射光谱法 (UVDRS) 比较了六种含曲卤糖的冻干缓冲体系的表观 pH 值。使用两种不同电离探针(分别为丁酸和溴甲酚紫)的 SSNMR 和 UVDRS 结果表明,与柠檬酸钠缓冲液中的冻干前溶液相比,表观酸度变化不大,但在磷酸二氢钾、磷酸钠和组氨酸缓冲液中观察到的变化较大。虽然两种方法的趋势相似,但两种方法的等效 pH 值(pHeq)却存在差异。本文讨论了造成差异的潜在原因。
{"title":"Determination of Solid-State Acidity of Lyophilized Trehalose Containing Citrate, Phosphate, and Histidine Buffers Using UV/VIS Diffuse Reflectance and Solid-State NMR Spectroscopy.","authors":"Ashley Lay-Fortenbery, Xiaoda Yuan, Lukáš Veselý, Dominik Heger, Evgenyi Shalaev, Yongchao Su, Eric Munson","doi":"10.1016/j.xphs.2024.09.019","DOIUrl":"https://doi.org/10.1016/j.xphs.2024.09.019","url":null,"abstract":"<p><p>Changes in the protonation state of lyophilized proteins can impact structural integrity, chemical stability, and propensity to aggregate upon reconstitution. When a buffer is chosen, the freezing/drying process may result in dramatic changes in the protonation state of the protein due to ionization shift of the buffer. In order to determine whether protonation shifts are occurring, ionizable probes can be added to the formulation. Optical probes (dyes) have shown dramatic ionization changes in lyophilized products, but it is unclear whether the pH indicator is uniform throughout the matrix and whether the change in the pH indicator actually mirrors drug ionization changes. In solid-state NMR (SSNMR) spectroscopy, the chemical shift of the carbonyl carbon in carboxylic acids is very sensitive to the ionization state of the acid. Therefore, SSNMR can be used to measure ionization changes in a lyophilized matrix by employing a small quantity of an isotopically-labeled carboxylic acid species in the formulation. This paper compares the apparent pH of six trehalose-containing lyophilized buffer systems using SSNMR and UV-Vis diffuse reflectance spectroscopy (UVDRS). Both SSNMR and UVDRS results using two different ionization probes (butyric acid and bromocresol purple, respectively) showed little change in apparent acidity compared to the pre-lyophilized solution in a sodium citrate buffer, but a greater change was observed in potassium phosphate, sodium phosphate, and histidine buffers. While the trends between the two methods were similar, there were differences in the numerical values of equivalent pH (pHeq) observed between the two methods. The potential causes contributing to the differences are discussed.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307976","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
Population pharmacokinetics and dosing simulations of meropenem in septic critically ill patients with complicated intra-abdominal infection or pneumonia. 美罗培南在患有复杂腹腔内感染或肺炎的化脓性重症患者中的群体药代动力学和剂量模拟。
IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-09-21 DOI: 10.1016/j.xphs.2024.09.011
Jingjing Huang, Tong Wu, Ruoming Tan, Yunqi Dai, Yuzhen Qiu, Haiwen Lu, Xiaoli Cao, Jialin Liu, Hongping Qu, Xiaoli Wang

Objectives: Meropenem pharmacokinetics (PK) may be altered in septic critically ill patients with complicated intra-abdominal infections (cIAI) and pneumonia. We aimed to evaluate the covariates affecting meropenem PK and the performance of different dosing regimens to optimize the PK/pharmacodynamic target.

Methods: Population PK analysis was performed using non-linear mixed-effects modeling. The final model was validated and used to simulate meropenem exposure to assess the probability of attaining the 100%ƒT>MIC target.

Results: Forty-six and 14 patients were respectively enrolled for PK analysis and external validation. A one-compartment linear model adequately described the data of 226 concentrations. The typical clearance (CL) and volume of distribution (Vd) were 9.69 L/h and 27.4 L, respectively. Septic shock from cIAI (cIASS) and actual body weight were significant covariates for meropenem Vd in addition to the influential covariates of creatinine clearance (CLCR-CG) and augmented renal clearance for CL. External validation showed the robustness and accuracy of this model. Simulation results proposed continuous infusion (CI) dosing regimens of meropenem against pathogens with MICs ≥ 2 mg/L in patients with cIASS and CLCR-CG ≥ 60 mL/min.

Conclusions: For the patients with cIASS and CLCR-CG ≥ 60 mL/min, CI meropenem is proposed for treatment of less sensitive pathogens with MICs ≥ 2 mg/L.

目的:患有复杂腹腔内感染(cIAI)和肺炎的败血症重症患者的美罗培南药代动力学(PK)可能会发生改变。我们旨在评估影响美罗培南药代动力学的协变量以及不同给药方案的性能,以优化药代动力学/药效学目标:采用非线性混合效应模型进行了人群 PK 分析。方法:采用非线性混合效应模型进行人群 PK 分析,验证最终模型并用于模拟美罗培南暴露,以评估达到 100%ƒT>MIC 目标的概率:分别有46名和14名患者参加了PK分析和外部验证。单室线性模型充分描述了226个浓度的数据。典型清除率(CL)和分布容积(Vd)分别为 9.69 升/小时和 27.4 升。除了影响CL的肌酐清除率(CLCR-CG)和增强肾脏清除率这两个协变量外,来自cIAI的脓毒性休克(cIASS)和实际体重也是影响美罗培南Vd的重要协变量。外部验证表明了该模型的稳健性和准确性。仿真结果表明,针对MICs≥2 mg/L的病原体,美罗培南可用于cIASS和CLCR-CG≥60 mL/min的患者:对于CIASS和CLCR-CG≥60 mL/min的患者,建议使用CI美罗培南治疗MIC≥2 mg/L的不太敏感的病原体。
{"title":"Population pharmacokinetics and dosing simulations of meropenem in septic critically ill patients with complicated intra-abdominal infection or pneumonia.","authors":"Jingjing Huang, Tong Wu, Ruoming Tan, Yunqi Dai, Yuzhen Qiu, Haiwen Lu, Xiaoli Cao, Jialin Liu, Hongping Qu, Xiaoli Wang","doi":"10.1016/j.xphs.2024.09.011","DOIUrl":"https://doi.org/10.1016/j.xphs.2024.09.011","url":null,"abstract":"<p><strong>Objectives: </strong>Meropenem pharmacokinetics (PK) may be altered in septic critically ill patients with complicated intra-abdominal infections (cIAI) and pneumonia. We aimed to evaluate the covariates affecting meropenem PK and the performance of different dosing regimens to optimize the PK/pharmacodynamic target.</p><p><strong>Methods: </strong>Population PK analysis was performed using non-linear mixed-effects modeling. The final model was validated and used to simulate meropenem exposure to assess the probability of attaining the 100%ƒT<sub>>MIC</sub> target.</p><p><strong>Results: </strong>Forty-six and 14 patients were respectively enrolled for PK analysis and external validation. A one-compartment linear model adequately described the data of 226 concentrations. The typical clearance (CL) and volume of distribution (Vd) were 9.69 L/h and 27.4 L, respectively. Septic shock from cIAI (cIASS) and actual body weight were significant covariates for meropenem Vd in addition to the influential covariates of creatinine clearance (CL<sub>CR</sub>-CG) and augmented renal clearance for CL. External validation showed the robustness and accuracy of this model. Simulation results proposed continuous infusion (CI) dosing regimens of meropenem against pathogens with MICs ≥ 2 mg/L in patients with cIASS and CL<sub>CR</sub>-CG ≥ 60 mL/min.</p><p><strong>Conclusions: </strong>For the patients with cIASS and CL<sub>CR</sub>-CG ≥ 60 mL/min, CI meropenem is proposed for treatment of less sensitive pathogens with MICs ≥ 2 mg/L.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307978","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
Engineering of Layer-by-layer Acetate-coated Paclitaxel Loaded Poly(lactide-co-glycolide) Acid Nanoparticles for Prostate Cancer Therapy- in vitro. 用于前列腺癌治疗的逐层醋酸纤维包覆紫杉醇聚乳酸-共聚甘醇酸纳米粒子的体外工程学研究
IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-09-21 DOI: 10.1016/j.xphs.2024.09.014
Albert Nguessan Ngo, Kierston K Chatman, Dezirae Douglas, Keb M Mosley-Kellum, Ke Wu, Jaydutt Vadgama

It is hypothesized that layer-by-layer acetate-coated Paclitaxel-loaded PLGA nanoparticles (F2) can be engineered to potentiate the effectiveness of Paclitaxel (PTX) on LNCaP, a human prostate cancer cell line. The core of the layer-by-layer NPs is formed by nanoprecipitation, and the shell of the NPs is engineered using the sodium acetate's unique coating mechanism and surface-active properties. The resulting nanoformulation physicochemical properties are characterized by Fourier Transform Infra-Red (FTIR), Differential Scanning Calorimetry (DSC) Transmission Electron Microscopy (TEM), NanoSight NS300, spectrophotometry, Korsmeyer-Peppas model, respectively. The NP's cytotoxicity on LNCaP is assessed by MTS assay. The DSC and the FTIR confirm SA's coating of the NPs. The particle's mean diameters (PMD) are 89.4±2.3- to 114.4±7.6 nm. The TEM shows a unique multilayer and spherical nanoparticle. The encapsulation efficiency of commonly PTX-loaded PLGA NPs (F1) and F2 are 84.37±2.71% and 86.74±2.22, respectively. The drug transport mechanism of F1 and F2 is anomalous transport and case II, respectively. F2 follows a zero-order release mechanism. The cell viability is 45.08±2.18% and 60.17±4.72% when LNCaP is treated with 10 µg/mL of F2 and F1, respectively, after 48 hours of exposure. F2 and F1 cell growth inhibition are dose-dependent. This unique process of engineering the layer-by-layer NPs will provide new horizons for developing future innovative nanoparticles for targeted prostate cancer therapy.

该研究假设,逐层醋酸钠包覆的紫杉醇负载PLGA纳米粒子(F2)可增强紫杉醇(PTX)对人类前列腺癌细胞系LNCaP的疗效。逐层 NPs 的核心是通过纳米沉淀形成的,而 NPs 的外壳则是利用醋酸钠独特的涂层机制和表面活性特性设计的。傅立叶变换红外光谱法(FTIR)、差示扫描量热法(DSC)、透射电子显微镜(TEM)、NanoSight NS300、分光光度法、Korsmeyer-Peppas 模型分别对所制备的纳米制剂的理化性质进行了表征。NP 对 LNCaP 的细胞毒性通过 MTS 试验进行评估。DSC 和傅立叶变换红外光谱证实了 NPs 上的 SA 涂层。颗粒的平均直径(PMD)为 89.4±2.3- 至 114.4±7.6 nm。TEM 显示了独特的多层球形纳米粒子。常见的PTX负载PLGA NPs(F1)和F2的包封效率分别为84.37±2.71%和86.74±2.22。F1和F2的药物转运机制分别为反常转运和情况II。F2 遵循零阶释放机制。用 10 µg/mL 的 F2 和 F1 处理 LNCaP 细胞 48 小时后,细胞存活率分别为 45.08±2.18% 和 60.17±4.72%。F2 和 F1 对细胞生长的抑制具有剂量依赖性。这种独特的逐层 NPs 工程工艺将为开发未来用于前列腺癌靶向治疗的创新纳米粒子提供新的前景。
{"title":"Engineering of Layer-by-layer Acetate-coated Paclitaxel Loaded Poly(lactide-co-glycolide) Acid Nanoparticles for Prostate Cancer Therapy- in vitro.","authors":"Albert Nguessan Ngo, Kierston K Chatman, Dezirae Douglas, Keb M Mosley-Kellum, Ke Wu, Jaydutt Vadgama","doi":"10.1016/j.xphs.2024.09.014","DOIUrl":"10.1016/j.xphs.2024.09.014","url":null,"abstract":"<p><p>It is hypothesized that layer-by-layer acetate-coated Paclitaxel-loaded PLGA nanoparticles (F2) can be engineered to potentiate the effectiveness of Paclitaxel (PTX) on LNCaP, a human prostate cancer cell line. The core of the layer-by-layer NPs is formed by nanoprecipitation, and the shell of the NPs is engineered using the sodium acetate's unique coating mechanism and surface-active properties. The resulting nanoformulation physicochemical properties are characterized by Fourier Transform Infra-Red (FTIR), Differential Scanning Calorimetry (DSC) Transmission Electron Microscopy (TEM), NanoSight NS300, spectrophotometry, Korsmeyer-Peppas model, respectively. The NP's cytotoxicity on LNCaP is assessed by MTS assay. The DSC and the FTIR confirm SA's coating of the NPs. The particle's mean diameters (PMD) are 89.4±2.3- to 114.4±7.6 nm. The TEM shows a unique multilayer and spherical nanoparticle. The encapsulation efficiency of commonly PTX-loaded PLGA NPs (F1) and F2 are 84.37±2.71% and 86.74±2.22, respectively. The drug transport mechanism of F1 and F2 is anomalous transport and case II, respectively. F2 follows a zero-order release mechanism. The cell viability is 45.08±2.18% and 60.17±4.72% when LNCaP is treated with 10 µg/mL of F2 and F1, respectively, after 48 hours of exposure. F2 and F1 cell growth inhibition are dose-dependent. This unique process of engineering the layer-by-layer NPs will provide new horizons for developing future innovative nanoparticles for targeted prostate cancer therapy.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307977","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
Quality risk management and data integrity in R&D laboratories supporting CMC lifecycle of biological products. 支持生物产品 CMC 生命周期的研发实验室的质量风险管理和数据完整性。
IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-09-21 DOI: 10.1016/j.xphs.2024.09.013
Brent S Kendrick, John P Gabrielson, Deanna Hunt, Merry Christie, Steven Bowen, Christina Vessely, Richard S Rogers, Chad Cleveland, Karl Maluf, Shawn Roach, Nadine Ritter

The development of pharmaceutical products is the critical bridge that moves a potential new medicine from academic discovery to applied treatment of patients. It translates an idea for a new drug to bench-level research on how it can be manufactured, formulated, characterized and controlled for use in non-clinical and early clinical trials. From pre-clinical R&D discovery work through the commercial launch, substantial R&D CMC data is generated to develop and optimize cGMP manufacturing and testing operations, while also supporting product comparability, elucidating product / impurity structures, assessing critical quality attributes, developing the drug delivery mode, and developing the product formulation for long-term stability. Significant R&D CMC work continues post-approval to support continuous improvement and market expansion of the commercial product. These activities are crucial elements of Product Lifecycle Management, and taken together, they comprise Pharmaceutical Quality or Chemistry, Manufacturing and Controls (CMC). The objective of this paper is to mitigate the regulatory ambiguity of R&D quality systems with practical, risk-based examples and recommendations when conducting supportive CMC studies for biological products. Making sound strategic CMC decisions under any circumstances assumes data from R&D studies are reliable, traceable, and complete. While there are specific regulatory guidelines on phase-appropriate cGMP activities, none exist for quality practices in R&D CMC laboratories conducting non-cGMP studies. Hindsight is not the time to discover that R&D studies lack key elements that would otherwise have allowed the data to be directly presented to regulators, if needed. There is a strong prospective business interest in protecting considerable investments made for CMC R&D studies. Therefore, establishment of a robust and stage-appropriate R&D laboratory quality system is essential for companies seeking to capitalize on prior knowledge, protect investments, and be prepared for accelerated approval pathways.

医药产品的开发是将潜在新药从学术发现转化为应用治疗病人的关键桥梁。它将新药的想法转化为如何生产、配制、表征和控制新药的台式研究,以便用于非临床和早期临床试验。从临床前研发发现工作到商业投放市场,都会产生大量的研发 CMC 数据,用于开发和优化 cGMP 生产和测试操作,同时还支持产品可比性、阐明产品/杂质结构、评估关键质量属性、开发给药模式以及开发长期稳定的产品配方。大量的研发 CMC 工作将在批准后继续进行,以支持商业产品的持续改进和市场拓展。这些活动是产品生命周期管理的关键要素,它们共同构成了药品质量或化学、制造和控制 (CMC)。本文旨在通过实用的、基于风险的示例和建议,在对生物产品进行支持性 CMC 研究时,减轻研发质量体系在监管方面的模糊性。要在任何情况下做出合理的 CMC 战略决策,研发研究的数据必须可靠、可追溯且完整。虽然有关于阶段性适当 cGMP 活动的具体监管指南,但没有任何指南适用于进行非 cGMP 研究的研发 CMC 实验室的质量实践。如果发现研发研究缺乏关键要素,而这些要素本可以在需要时直接向监管机构提交数据,那么现在就不能事后诸葛亮了。保护对 CMC 研发研究的大量投资,是未来企业的重大利益所在。因此,建立健全的、与阶段相适应的研发实验室质量体系,对于希望利用先前知识、保护投资并为加速审批途径做好准备的公司来说至关重要。
{"title":"Quality risk management and data integrity in R&D laboratories supporting CMC lifecycle of biological products.","authors":"Brent S Kendrick, John P Gabrielson, Deanna Hunt, Merry Christie, Steven Bowen, Christina Vessely, Richard S Rogers, Chad Cleveland, Karl Maluf, Shawn Roach, Nadine Ritter","doi":"10.1016/j.xphs.2024.09.013","DOIUrl":"10.1016/j.xphs.2024.09.013","url":null,"abstract":"<p><p>The development of pharmaceutical products is the critical bridge that moves a potential new medicine from academic discovery to applied treatment of patients. It translates an idea for a new drug to bench-level research on how it can be manufactured, formulated, characterized and controlled for use in non-clinical and early clinical trials. From pre-clinical R&D discovery work through the commercial launch, substantial R&D CMC data is generated to develop and optimize cGMP manufacturing and testing operations, while also supporting product comparability, elucidating product / impurity structures, assessing critical quality attributes, developing the drug delivery mode, and developing the product formulation for long-term stability. Significant R&D CMC work continues post-approval to support continuous improvement and market expansion of the commercial product. These activities are crucial elements of Product Lifecycle Management, and taken together, they comprise Pharmaceutical Quality or Chemistry, Manufacturing and Controls (CMC). The objective of this paper is to mitigate the regulatory ambiguity of R&D quality systems with practical, risk-based examples and recommendations when conducting supportive CMC studies for biological products. Making sound strategic CMC decisions under any circumstances assumes data from R&D studies are reliable, traceable, and complete. While there are specific regulatory guidelines on phase-appropriate cGMP activities, none exist for quality practices in R&D CMC laboratories conducting non-cGMP studies. Hindsight is not the time to discover that R&D studies lack key elements that would otherwise have allowed the data to be directly presented to regulators, if needed. There is a strong prospective business interest in protecting considerable investments made for CMC R&D studies. Therefore, establishment of a robust and stage-appropriate R&D laboratory quality system is essential for companies seeking to capitalize on prior knowledge, protect investments, and be prepared for accelerated approval pathways.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307979","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
Visualisation and quantification of subcutaneous injections of different volumes, viscosities and injection rates: An ex-vivo micro-CT study. 不同体积、粘度和注射速度的皮下注射的可视化和量化:体外显微 CT 研究。
IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-09-19 DOI: 10.1016/j.xphs.2024.08.019
Joel Gresham, Gerard Bruin, Marie Picci, Karoline Bechtold-Peters, Thomas Dimke, Evan Davies, Kasia Błażejczyk, Wouter Willekens, Heleen Fehervary, Greetje Vande Velde

The effects of subcutaneous (SC) injection parameters such as drug formulation volume, viscosity and injection rate on therapeutic performance and tolerability have not been established for any drug product. In this study four groups of SC injections were performed on fresh ex vivo minipig abdominal tissue samples, varying volume (0.5-1 mL), viscosity (1-11 cP) and rate (0.02-0.1 mL/s). Micro-CT provided high resolution (50 micron) imaging of the SC tissues before and after injection, enabling a detailed 3D visualisation and analysis of how both injection parameters and tissue microstructure influence spatial distribution of injectables. We found that volume was the only significant factor for spatial distribution of injectate within our design space, and there were no significant factors for tissue backpressure. Variability within test groups was typically greater than differences between group means. Accordingly, whilst the higher viscosity formulations consistently exhibited reduced spatial distribution, the sample size was not large enough to establish confidence in this result. Comparing our findings to clinical evidence, we conclude that injection site and depth are more likely to influence PK and bioavailability than volume, viscosity and rate within our experimental space.

皮下注射(SC)参数(如药物配方体积、粘度和注射速度)对治疗效果和耐受性的影响尚未在任何药物产品中得到证实。本研究对新鲜的活体小鼠腹部组织样本进行了四组皮下注射,注射量(0.5-1 mL)、粘度(1-11 cP)和注射速度(0.02-0.1 mL/s)各不相同。显微计算机断层扫描提供了注射前后 SC 组织的高分辨率(50 微米)成像,实现了详细的三维可视化,并分析了注射参数和组织微观结构如何影响注射剂的空间分布。我们发现,在我们的设计空间内,体积是影响注射剂空间分布的唯一重要因素,而组织背压则没有重要因素。测试组内的变异通常大于组间平均值的差异。因此,虽然粘度较高的配方始终表现出较低的空间分布,但由于样本量不够大,无法确定这一结果的可信度。将我们的研究结果与临床证据进行比较后,我们得出结论:在我们的实验空间内,注射部位和深度比容量、粘度和速率更有可能影响 PK 和生物利用度。
{"title":"Visualisation and quantification of subcutaneous injections of different volumes, viscosities and injection rates: An ex-vivo micro-CT study.","authors":"Joel Gresham, Gerard Bruin, Marie Picci, Karoline Bechtold-Peters, Thomas Dimke, Evan Davies, Kasia Błażejczyk, Wouter Willekens, Heleen Fehervary, Greetje Vande Velde","doi":"10.1016/j.xphs.2024.08.019","DOIUrl":"10.1016/j.xphs.2024.08.019","url":null,"abstract":"<p><p>The effects of subcutaneous (SC) injection parameters such as drug formulation volume, viscosity and injection rate on therapeutic performance and tolerability have not been established for any drug product. In this study four groups of SC injections were performed on fresh ex vivo minipig abdominal tissue samples, varying volume (0.5-1 mL), viscosity (1-11 cP) and rate (0.02-0.1 mL/s). Micro-CT provided high resolution (50 micron) imaging of the SC tissues before and after injection, enabling a detailed 3D visualisation and analysis of how both injection parameters and tissue microstructure influence spatial distribution of injectables. We found that volume was the only significant factor for spatial distribution of injectate within our design space, and there were no significant factors for tissue backpressure. Variability within test groups was typically greater than differences between group means. Accordingly, whilst the higher viscosity formulations consistently exhibited reduced spatial distribution, the sample size was not large enough to establish confidence in this result. Comparing our findings to clinical evidence, we conclude that injection site and depth are more likely to influence PK and bioavailability than volume, viscosity and rate within our experimental space.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289721","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
Understanding Excipient-Induced Crystallization of Spray-Dried Amorphous Solid Dispersion. 了解喷雾干燥无定形固体分散体的赋形剂诱导结晶。
IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-09-19 DOI: 10.1016/j.xphs.2024.08.024
Dongyue Yu, Meng Li, Stephen W Hoag, Haichen Nie

This study investigates the compatibility of excipients with the model system SDI-X and their role in the induced crystallization of the amorphous compound-X in tablet formulations. We aimed to establish a straightforward and practical screening approach for evaluating excipient-induced crystallization of SDI in tablet matrices. Three methodologies-binary powder mixture, binary compact, and bilayer tablets-were employed to qualitatively and quantitatively evaluate the recrystallization of SDI-X with various excipients under accelerated storage conditions. The results demonstrated that binary compacts, providing direct physical contact between SDI-X and excipients, are superior in reflecting realistic drug-excipient contact within pharmaceutical tablets, enabling a more accurate assessment of excipient-induced crystallization for SDI-X. In contrast, the broadly used conventional binary blends can significantly underestimate this risk due to insufficient proximity. In addition, the bilayer tablets further confirmed that crystallization initiates at the contact surface between SDI-X and the excipients. The study highlighted that not only hygroscopicity but also the type of excipient and its physical contact with SDI-X significantly influence the recrystallization extent and rate of SDI-X. Interestingly, less hygroscopic diluents such as mannitol and lactose induced much higher levels of crystallization of SDIs, contrary to expectations based on moisture content alone. This suggests that the excipient type and contact surface are more critical in inducing recrystallization than just the level of moisture. The findings emphasize the need for careful excipient selection, study design, and sample preparation to enable appropriate assessments of SDI-excipient compatibility.

本研究调查了辅料与模型体系 SDI-X 的兼容性及其在片剂中诱导无定形化合物-X 结晶的作用。我们旨在建立一种简单实用的筛选方法,用于评估片剂基质中辅料诱导的 SDI 结晶。我们采用了三种方法--二元粉末混合物、二元压制物和双层片剂--来定性和定量评估 SDI-X 与各种辅料在加速储存条件下的再结晶情况。结果表明,二元压制物能使 SDI-X 与辅料直接发生物理接触,在反映药片内药物与辅料的真实接触方面更胜一筹,从而能更准确地评估辅料诱导的 SDI-X 结晶。相比之下,广泛使用的传统二元共混物会因不够接近而大大低估这种风险。此外,双层片剂进一步证实,结晶始于 SDI-X 与辅料的接触面。该研究强调,不仅吸湿性,辅料的类型及其与 SDI-X 的物理接触也会显著影响 SDI-X 的再结晶程度和速度。有趣的是,吸湿性较低的稀释剂(如甘露醇和乳糖)诱导的 SDI 结晶水平要高得多,这与仅根据水分含量得出的预期相反。这表明,在诱导再结晶方面,辅料类型和接触面比水分含量更为关键。这些发现强调了谨慎选择辅料、研究设计和样品制备的必要性,以便对 SDI 与辅料的兼容性进行适当的评估。
{"title":"Understanding Excipient-Induced Crystallization of Spray-Dried Amorphous Solid Dispersion.","authors":"Dongyue Yu, Meng Li, Stephen W Hoag, Haichen Nie","doi":"10.1016/j.xphs.2024.08.024","DOIUrl":"10.1016/j.xphs.2024.08.024","url":null,"abstract":"<p><p>This study investigates the compatibility of excipients with the model system SDI-X and their role in the induced crystallization of the amorphous compound-X in tablet formulations. We aimed to establish a straightforward and practical screening approach for evaluating excipient-induced crystallization of SDI in tablet matrices. Three methodologies-binary powder mixture, binary compact, and bilayer tablets-were employed to qualitatively and quantitatively evaluate the recrystallization of SDI-X with various excipients under accelerated storage conditions. The results demonstrated that binary compacts, providing direct physical contact between SDI-X and excipients, are superior in reflecting realistic drug-excipient contact within pharmaceutical tablets, enabling a more accurate assessment of excipient-induced crystallization for SDI-X. In contrast, the broadly used conventional binary blends can significantly underestimate this risk due to insufficient proximity. In addition, the bilayer tablets further confirmed that crystallization initiates at the contact surface between SDI-X and the excipients. The study highlighted that not only hygroscopicity but also the type of excipient and its physical contact with SDI-X significantly influence the recrystallization extent and rate of SDI-X. Interestingly, less hygroscopic diluents such as mannitol and lactose induced much higher levels of crystallization of SDIs, contrary to expectations based on moisture content alone. This suggests that the excipient type and contact surface are more critical in inducing recrystallization than just the level of moisture. The findings emphasize the need for careful excipient selection, study design, and sample preparation to enable appropriate assessments of SDI-excipient compatibility.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289719","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
Use of differential scanning calorimetry as a rapid, effective in-process check method for impurity quantitation of an early clinical batch of Giredestrant (GDC-9545). 使用差示示踪表量热法作为早期临床批次吉瑞司群 (GDC-9545) 杂质定量的一种快速、有效的过程中检查方法。
IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-09-19 DOI: 10.1016/j.xphs.2024.09.003
Paroma Chakravarty, Karthik Nagapudi

Giredestrant (GDC-9545) is a selective estrogen receptor degrader (SERD) that was developed for treatment of ER+/HER2- metastatic breast cancer. An anhydrous crystalline tartrate salt was identified as the solid form suitable for clinical development. An early clinical batch of the active pharmaceutical ingredient (API)/drug substance failed to pass the GMP purity specifications owing to the presence of a substantial amount of high molecular weight impurities (oligomers), as determined by size exclusion chromatography. Several trial rework batches were manufactured using various re-slurry and recrystallization conditions to purge impurities in the drug substance to adhere to purity specifications. Based on the melting point depression of the API in presence of oligomers in these rework batches, a differential scanning calorimetry method was developed to quantify impurity content as a function of melting point onset of the API. This thermal analysis method was used as a surrogate for chromatography as a rapid, effective in-process check method for impurity quantitation to enable the timely release of the final reworked clinical batch. Post release, the % w/w oligomer value determined by calorimetry was in excellent agreement to that obtained by size exclusion chromatography.

Giredestrant (GDC-9545) 是一种选择性雌激素受体降解剂 (SERD),用于治疗 ER+/HER2- 转移性乳腺癌。无水结晶酒石酸盐被确定为适合临床开发的固体形式。经尺寸排阻色谱法测定,由于存在大量高分子量杂质(低聚物),早期临床批次的活性药物成分(API)/药物物质未能通过 GMP 纯度规范。为了清除药物中的杂质,使其符合纯度规范,我们使用各种重浆和重结晶条件试制了几批返工产品。根据这些返修批次中存在低聚物时原料药熔点降低的情况,开发了一种差示扫描量热法,用于量化作为原料药熔点起始函数的杂质含量。这种热分析方法被用作色谱法的替代方法,是一种快速、有效的杂质定量过程中检查方法,以便及时释放最终返工的临床批次。释放后,通过量热法确定的低聚物重量百分比值与通过尺寸排阻色谱法确定的值非常吻合。
{"title":"Use of differential scanning calorimetry as a rapid, effective in-process check method for impurity quantitation of an early clinical batch of Giredestrant (GDC-9545).","authors":"Paroma Chakravarty, Karthik Nagapudi","doi":"10.1016/j.xphs.2024.09.003","DOIUrl":"10.1016/j.xphs.2024.09.003","url":null,"abstract":"<p><p>Giredestrant (GDC-9545) is a selective estrogen receptor degrader (SERD) that was developed for treatment of ER+/HER2- metastatic breast cancer. An anhydrous crystalline tartrate salt was identified as the solid form suitable for clinical development. An early clinical batch of the active pharmaceutical ingredient (API)/drug substance failed to pass the GMP purity specifications owing to the presence of a substantial amount of high molecular weight impurities (oligomers), as determined by size exclusion chromatography. Several trial rework batches were manufactured using various re-slurry and recrystallization conditions to purge impurities in the drug substance to adhere to purity specifications. Based on the melting point depression of the API in presence of oligomers in these rework batches, a differential scanning calorimetry method was developed to quantify impurity content as a function of melting point onset of the API. This thermal analysis method was used as a surrogate for chromatography as a rapid, effective in-process check method for impurity quantitation to enable the timely release of the final reworked clinical batch. Post release, the % w/w oligomer value determined by calorimetry was in excellent agreement to that obtained by size exclusion chromatography.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289720","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
Leadership and mentorship of Professor Lynne S. Taylor: A personal account from former mentees. Lynne S. Taylor 教授的领导力和导师精神:前学员的亲身经历。
IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-09-17 DOI: 10.1016/j.xphs.2024.09.009
Amjad Alhalaweh, Anura S Indulkar, Laura I Mosquera-Giraldo, Hitesh S Purohit, Shweta A Raina, Niraj S Trasi, Håkan Wikström

This article highlights the profound impact of Professor Lynne S. Taylor, Retter Distinguished Professor of Pharmacy at Purdue University, on her mentees in terms of scientific and professional experience. The former students summarize some of her important contributions, including her emphasis on critical thinking, collaboration, and work-life balance, which have shaped her students into dedicated scientists advancing the pharmaceutical sciences. This acknowledgment recognizes her valuable impact on both her students and the broader scientific community.

本文重点介绍了普渡大学雷特特聘药学教授琳恩-泰勒(Lynne S. Taylor)在科学和专业经验方面对她的学生产生的深远影响。前学生们总结了她的一些重要贡献,包括她对批判性思维、合作和工作与生活平衡的重视,这些贡献将她的学生们塑造成了致力于推动制药科学发展的科学家。这是对她对学生和更广泛的科学界所产生的宝贵影响的认可。
{"title":"Leadership and mentorship of Professor Lynne S. Taylor: A personal account from former mentees.","authors":"Amjad Alhalaweh, Anura S Indulkar, Laura I Mosquera-Giraldo, Hitesh S Purohit, Shweta A Raina, Niraj S Trasi, Håkan Wikström","doi":"10.1016/j.xphs.2024.09.009","DOIUrl":"10.1016/j.xphs.2024.09.009","url":null,"abstract":"<p><p>This article highlights the profound impact of Professor Lynne S. Taylor, Retter Distinguished Professor of Pharmacy at Purdue University, on her mentees in terms of scientific and professional experience. The former students summarize some of her important contributions, including her emphasis on critical thinking, collaboration, and work-life balance, which have shaped her students into dedicated scientists advancing the pharmaceutical sciences. This acknowledgment recognizes her valuable impact on both her students and the broader scientific community.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289717","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
Application of a UV-vis spectrometer to investigate the effect of dissolution media on the diffusivity of small molecules and proteins. 应用紫外可见光谱仪研究溶解介质对小分子和蛋白质扩散性的影响。
IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-09-14 DOI: 10.1016/j.xphs.2024.09.008
Hao Lou, Gang Hu, Xi Luan, Jill M Steinbach-Rankins, Michael J Hageman

To date, the commonly used methods for diffusion coefficient measurements have some hurdles that prevent them from being widely applied in pharmaceutical laboratories. This study aimed to modify a method developed by di Cagno et al. based on the use of a UV-Vis spectrometer and apply the method to investigate the effect of dissolution media on the diffusivity of small molecules and proteins. A total of five small molecules and two proteins in different aqueous media and polymer solutions were investigated in this study. By attaching a 3D-printed cover with an open slit to a standard UV-Vis cuvette, the incident UV light could only pass through the open slit to measure the local drug concentration. During the diffusion experiment, drug molecules diffused from the cuvette bottom to the slit. According to the concentration measured as a function of time, diffusion coefficient was calculated based on Fick's law of diffusion using the analytical and numerical approaches. As a result, diffusion coefficients could be accurately measured with high reproducibility. The results also suggested that different media could affect the diffusion coefficients of small molecules by < 10% and proteins by < 15%. Since the UV-Vis spectrometer is a routine instrument, this method can potentially be employed by many pharmaceutical laboratories for diffusion coefficient measurements.

迄今为止,常用的扩散系数测量方法都存在一些障碍,无法广泛应用于制药实验室。本研究旨在修改 di Cagno 等人基于紫外可见光谱仪开发的方法,并将其应用于研究溶解介质对小分子和蛋白质扩散系数的影响。本研究共对不同水介质和聚合物溶液中的五种小分子和两种蛋白质进行了研究。通过在标准紫外可见比色皿上安装一个带有开口缝隙的 3D 打印盖,入射紫外光只能通过开口缝隙来测量局部药物浓度。在扩散实验中,药物分子从比色皿底部向狭缝扩散。根据测量到的浓度与时间的函数关系,利用分析和数值方法,根据菲克扩散定律计算出扩散系数。结果表明,扩散系数可以精确测量,并且具有很高的重现性。结果还表明,不同介质对小分子扩散系数的影响小于 10%,对蛋白质的影响小于 15%。由于紫外可见光谱仪是一种常规仪器,这种方法有可能被许多制药实验室用于扩散系数的测量。
{"title":"Application of a UV-vis spectrometer to investigate the effect of dissolution media on the diffusivity of small molecules and proteins.","authors":"Hao Lou, Gang Hu, Xi Luan, Jill M Steinbach-Rankins, Michael J Hageman","doi":"10.1016/j.xphs.2024.09.008","DOIUrl":"https://doi.org/10.1016/j.xphs.2024.09.008","url":null,"abstract":"<p><p>To date, the commonly used methods for diffusion coefficient measurements have some hurdles that prevent them from being widely applied in pharmaceutical laboratories. This study aimed to modify a method developed by di Cagno et al. based on the use of a UV-Vis spectrometer and apply the method to investigate the effect of dissolution media on the diffusivity of small molecules and proteins. A total of five small molecules and two proteins in different aqueous media and polymer solutions were investigated in this study. By attaching a 3D-printed cover with an open slit to a standard UV-Vis cuvette, the incident UV light could only pass through the open slit to measure the local drug concentration. During the diffusion experiment, drug molecules diffused from the cuvette bottom to the slit. According to the concentration measured as a function of time, diffusion coefficient was calculated based on Fick's law of diffusion using the analytical and numerical approaches. As a result, diffusion coefficients could be accurately measured with high reproducibility. The results also suggested that different media could affect the diffusion coefficients of small molecules by < 10% and proteins by < 15%. Since the UV-Vis spectrometer is a routine instrument, this method can potentially be employed by many pharmaceutical laboratories for diffusion coefficient measurements.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289712","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
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.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1