Filtration of highly viscous pharmaceutical solutions exhibits a non-linear relationship between pump speed and flow rate. To systematically investigate this phenomenon, experiments were conducted across a wide range of solution viscosities (1.0-25.7 cP) and pump speeds (10-120 rpm). In 1.0 and 2.5 cP solutions, flow rate increases linearly with pump speed. However, for solutions with viscosity ≥ 5 cP, the relationship exhibits a linear region followed by a nonlinear decline beyond a critical inflection point. Notably, this inflection point shifts to lower pump speeds as viscosity increases. Four different models were fitted and compared, a segmented kinetic model was developed to describe the relationship between flow rate, pump speed, and viscosity, capturing both linear and nonlinear regimes. By identifying a consistent inflection point at approximately 19 psi and applying a power-law function to characterize viscosity-dependent pump speed, Darcy's law and theoretical flow limits were integrated to enable direct calculation of key process parameters. This model achieved an excellent fit (R²: 0.998), reduced prediction error (MAPE: 3.2%, MAE: 0.229, RMSE: 0.303), and revealed consistent kinetic behavior. These findings provide a predictive method for optimizing filtration performance, improving technology transfer, and enhancing scale-up reliability in biopharmaceutical manufacturing.
{"title":"Modeling Filtration Flow Rate in Peristaltic Pump Systems for High-Viscosity Bovine Serum Albumin: A Multivariate Nonlinear Approach.","authors":"Jianwei Chang, Yu Zhang, Fang Zhang, Yu Wang, Wei Qin, Tingting Wang, Qizhou Chen, Jeremy Guo","doi":"10.1016/j.xphs.2025.104113","DOIUrl":"https://doi.org/10.1016/j.xphs.2025.104113","url":null,"abstract":"<p><p>Filtration of highly viscous pharmaceutical solutions exhibits a non-linear relationship between pump speed and flow rate. To systematically investigate this phenomenon, experiments were conducted across a wide range of solution viscosities (1.0-25.7 cP) and pump speeds (10-120 rpm). In 1.0 and 2.5 cP solutions, flow rate increases linearly with pump speed. However, for solutions with viscosity ≥ 5 cP, the relationship exhibits a linear region followed by a nonlinear decline beyond a critical inflection point. Notably, this inflection point shifts to lower pump speeds as viscosity increases. Four different models were fitted and compared, a segmented kinetic model was developed to describe the relationship between flow rate, pump speed, and viscosity, capturing both linear and nonlinear regimes. By identifying a consistent inflection point at approximately 19 psi and applying a power-law function to characterize viscosity-dependent pump speed, Darcy's law and theoretical flow limits were integrated to enable direct calculation of key process parameters. This model achieved an excellent fit (R²: 0.998), reduced prediction error (MAPE: 3.2%, MAE: 0.229, RMSE: 0.303), and revealed consistent kinetic behavior. These findings provide a predictive method for optimizing filtration performance, improving technology transfer, and enhancing scale-up reliability in biopharmaceutical manufacturing.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104113"},"PeriodicalIF":3.8,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145695989","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}
Pub Date : 2025-12-03DOI: 10.1016/j.xphs.2025.104115
Xian Wu , Xiangxiang Hu , Yiqin Li , Hong-Bo Pang
Extracellular vesicles (EVs) play a vital role in mediating intercellular communication and regulatory processes. Using a three-dimensional (3D) intercellular exchange assay, we previously demonstrated that EVs facilitate the intercellular transfer of nanoparticles (NPs) among cells in vitro and are essential for the efficient delivery of NPs in vivo. This assay was further employed to identify small molecules capable of regulating the intercellular exchange process. However, the original assay relied on fluorescence labeling and flow cytometry for detection, which posed limitations for adaptation to high-throughput screening (HTS) platforms. In this study, we developed an enhanced intercellular exchange assay based on horseradish peroxidase (HRP) labeling. Specifically, cell-penetrating peptide-conjugated silver nanoparticles (CPP-AgNPs) were labeled with HRP, allowing signal amplification through the enzymatic reaction between HRP and its substrate. This modification significantly improved the signal-to-noise ratio (S/N) to approximately 6:1. Additionally, we optimized the gel composition within the assay system to ensure compatibility with HTS workflows. Using this HRP-based assay, we validated that LDN-214117, a previously identified agonist of intercellular exchange, significantly promoted the transfer of CPP-AgNPs between various cell pairs. Collectively, our work presents a novel, rapid, and versatile platform for identifying modulators of intercellular exchange in a high-throughput format.
{"title":"Development of HRP-based 3D intercellular exchange assay for high throughput screening","authors":"Xian Wu , Xiangxiang Hu , Yiqin Li , Hong-Bo Pang","doi":"10.1016/j.xphs.2025.104115","DOIUrl":"10.1016/j.xphs.2025.104115","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) play a vital role in mediating intercellular communication and regulatory processes. Using a three-dimensional (3D) intercellular exchange assay, we previously demonstrated that EVs facilitate the intercellular transfer of nanoparticles (NPs) among cells <em>in vitro</em> and are essential for the efficient delivery of NPs <em>in vivo</em>. This assay was further employed to identify small molecules capable of regulating the intercellular exchange process. However, the original assay relied on fluorescence labeling and flow cytometry for detection, which posed limitations for adaptation to high-throughput screening (HTS) platforms. In this study, we developed an enhanced intercellular exchange assay based on horseradish peroxidase (HRP) labeling. Specifically, cell-penetrating peptide-conjugated silver nanoparticles (CPP-AgNPs) were labeled with HRP, allowing signal amplification through the enzymatic reaction between HRP and its substrate. This modification significantly improved the signal-to-noise ratio (S/N) to approximately 6:1. Additionally, we optimized the gel composition within the assay system to ensure compatibility with HTS workflows. Using this HRP-based assay, we validated that LDN-214117, a previously identified agonist of intercellular exchange, significantly promoted the transfer of CPP-AgNPs between various cell pairs. Collectively, our work presents a novel, rapid, and versatile platform for identifying modulators of intercellular exchange in a high-throughput format.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 2","pages":"Article 104115"},"PeriodicalIF":3.8,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687535","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}
Pub Date : 2025-12-01DOI: 10.1016/j.xphs.2025.103762
Maame Esi Baidoo, Jonghoon Kang
{"title":"Thermodynamic analysis of synergistic effect of cyclodextrins and electrolytes on the solubility of aromatic amino acids","authors":"Maame Esi Baidoo, Jonghoon Kang","doi":"10.1016/j.xphs.2025.103762","DOIUrl":"10.1016/j.xphs.2025.103762","url":null,"abstract":"","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 12","pages":"Article 103762"},"PeriodicalIF":3.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670184","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}
Pub Date : 2025-12-01DOI: 10.1016/j.xphs.2025.103821
Hwee Jing Ong, Fernando Alvarez-Nunez, Teresa Carvajal, Samuel H. Yalkowsky
{"title":"A cluster of articles in memory of Rodolfo Pinal, Ph.D.","authors":"Hwee Jing Ong, Fernando Alvarez-Nunez, Teresa Carvajal, Samuel H. Yalkowsky","doi":"10.1016/j.xphs.2025.103821","DOIUrl":"10.1016/j.xphs.2025.103821","url":null,"abstract":"","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 12","pages":"Article 103821"},"PeriodicalIF":3.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998296","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}
Pub Date : 2025-12-01DOI: 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.
{"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}
Pub Date : 2025-12-01DOI: 10.1016/j.xphs.2025.103808
Kinam Park
{"title":"Professor Rodolfo Pinal: A man of the Tao","authors":"Kinam Park","doi":"10.1016/j.xphs.2025.103808","DOIUrl":"10.1016/j.xphs.2025.103808","url":null,"abstract":"","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 12","pages":"Article 103808"},"PeriodicalIF":3.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972784","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}
Pub Date : 2025-12-01DOI: 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.
{"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}
Pub Date : 2025-12-01DOI: 10.1016/j.xphs.2025.103926
Bradley D. Anderson , Daniel J.A. Crommelin , James N. Herron
{"title":"In memory of Professor William I. Higuchi (1931–2024)","authors":"Bradley D. Anderson , Daniel J.A. Crommelin , James N. Herron","doi":"10.1016/j.xphs.2025.103926","DOIUrl":"10.1016/j.xphs.2025.103926","url":null,"abstract":"","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 12","pages":"Article 103926"},"PeriodicalIF":3.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144731905","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}
Pub Date : 2025-12-01DOI: 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.
{"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}
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