Compatibility of parenteral nutrition admixture (PNA) and intravenous medications (IVMs) is a major consideration for clinicians and clinical pharmacists, especially when concurrent administration of PNA with IVMs is unavoidable. This is relatively common in children and neonates, where limited vascular access can be challenging. The purpose of this paper is to create a risk assessment tool that will assist clinical judgment in evaluating the potential incompatibility risk between PNA media and the IVMs when they are administered together through the same intravenous line. The tool will help to provide a more structured approach for healthcare professionals involved in the provision and administration of PNA to assess the risk of incompatibility of IVMs with PNA media.
{"title":"Risk assessment tool for compatibility of concurrent administration of intravenous medications with parenteral nutrition admixture","authors":"Mahmoud Farhan , Joanne Bennett , Anne Cram , Naomi McCallion , Fiona O’Brien","doi":"10.1016/j.ejpb.2024.114614","DOIUrl":"10.1016/j.ejpb.2024.114614","url":null,"abstract":"<div><div>Compatibility of parenteral nutrition admixture (PNA) and intravenous medications (IVMs) is a major consideration for clinicians and clinical pharmacists, especially when concurrent administration of PNA with IVMs is unavoidable. This is relatively common in children and neonates, where limited vascular access can be challenging. The purpose of this paper is to create a risk assessment tool that will assist clinical judgment in evaluating the potential incompatibility risk between PNA media and the IVMs when they are administered together through the same intravenous line. The tool will help to provide a more structured approach for healthcare professionals involved in the provision and administration of PNA to assess the risk of incompatibility of IVMs with PNA media.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"207 ","pages":"Article 114614"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-31DOI: 10.1016/j.ejpb.2025.114653
Yueqiang Zhao
The solubility of drugs in biological fluids is associated with pharmacokinetic properties (absorption, biotransformation and excretion), efficacy and toxicity. It is a fascinating and challenging task to uncover the intrinsic reason underlying the dissolution behavior of pharmaceuticals. The classical thermodynamic method estimates the drug solubility in liquid solvent via Solid-Liquid Equilibrium (SLE) equation plus activity coefficient models (UNIFAC, COSMO-RS, COSMO-SAC, etc), where the molar dissolution energy (partial molar excess Gibbs energy) of solute molecules in solution is calculated through activity coefficient models. The new method predicts the solute solubility via the transfer free energy (from solid phase to liquid phase) of solute molecules in terms of fusion properties and solute–solvent (liquid–liquid) interfacial tension, where the molar dissolution energy of solute molecules is determined by solute–solvent interfacial tension, and the solute–solvent (liquid–liquid) interfacial tension is obtained from the cohesive energy calculation results of COSMO-UCE (Conductor-Like Screening Model for Universal Cohesive Energy estimation) based merely on the molecular structure. The application of this model in solubility prediction of solid drugs in pure liquid solvents has been verified extensively with successful results. This model yields similar solute solubility representation performance as that of SLE + UNIFAC, and obtains much better solubility prediction results than SLE + COSMO-SAC.
{"title":"New solubility model for solid drugs in pure solvents based on solute-solvent interfacial tension","authors":"Yueqiang Zhao","doi":"10.1016/j.ejpb.2025.114653","DOIUrl":"10.1016/j.ejpb.2025.114653","url":null,"abstract":"<div><div>The solubility of drugs in biological fluids is associated with pharmacokinetic properties (absorption, biotransformation and excretion), efficacy and toxicity. It is a fascinating and challenging task to uncover the intrinsic reason underlying the dissolution behavior of pharmaceuticals. The classical thermodynamic method estimates the drug solubility in liquid solvent via Solid-Liquid Equilibrium (SLE) equation plus activity coefficient models (UNIFAC, COSMO-RS, COSMO-SAC, etc), where the molar dissolution energy (partial molar excess Gibbs energy) of solute molecules in solution is calculated through activity coefficient models. The new method predicts the solute solubility via the transfer free energy (from solid phase to liquid phase) of solute molecules in terms of fusion properties and solute–solvent (liquid–liquid) interfacial tension, where the molar dissolution energy of solute molecules is determined by solute–solvent interfacial tension, and the solute–solvent (liquid–liquid) interfacial tension is obtained from the cohesive energy calculation results of COSMO-UCE (Conductor-Like Screening Model for Universal Cohesive Energy estimation) based merely on the molecular structure. The application of this model in solubility prediction of solid drugs in pure liquid solvents has been verified extensively with successful results. This model yields similar solute solubility representation performance as that of SLE + UNIFAC, and obtains much better solubility prediction results than SLE + COSMO-SAC.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"208 ","pages":"Article 114653"},"PeriodicalIF":4.4,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The development of a direct compression excipient with extended-release property is crucial for improving tablet manufacturing and drug delivery. This research focuses on developing a novel co-processed excipient composed of rice starch (RS), methylcellulose (MC), and colloidal silicon dioxide (CSD) using a wet granulation technique. The ratios of RS: MC (1.66:1–1:3) and CSD concentrations (1.0 – 8.26 %) on the properties of co-processed material were evaluated. The RS co-processed with MC and CS (RMSs) formed agglomerate particles (199 – 294 μm of average particle size) with irregular shapes and rough surfaces due to the wet granulation technique. FT-IR spectroscopy confirmed that there was no change in the chemical structure during co-processing, while the amorphous characteristic of MC considerably decreased the crystallinity of the RMSs. The increase in the particle size and the bulk density of the RMSs improved material flowability (17 – 18° for angle of repose) and facilitated particle rearrangement during die filling. RS plasticity promoted material compressibility, while the brittleness of CSD contributed to the increased tablet tensile strength. The elastic recovery of RMSs relied on the ratio of RS, which facilitated permanent bonding, whereas incorporating CSD reduced the lubricant sensitivity of material. The co-processing with MC significantly improved material swellability and effectively maintained the polymer matrix for a long period in media with pH 1.2, 4.5, and 7.5. The in vitro release study confirmed the ability of RMSs to prolong drug release from the matrix tablets, where the cumulative drug release of RMS-2 tablets met the specification and conformed with Higuchi model. Among the RMSs, RMS-2 (RS co-processed with 48.7 % MC and 2.68 % CSD) exhibited the optimal ratio of co-processing, as it demonstrated more favorable compression behavior and extended-release property than other RMSs. These findings indicated that RMSs could potentially be used as a direct compression excipient with extended-release properties.
{"title":"A novel directly compressible co-processed excipient, based-on rice starch for extended-release of tablets","authors":"Karnkamol Trisopon , Nisit Kittipongpatana , Pimjai Doungsaard , Neungreuthai Chomchoei , Ornanong Suwannapakul Kittipongpatana","doi":"10.1016/j.ejpb.2024.114623","DOIUrl":"10.1016/j.ejpb.2024.114623","url":null,"abstract":"<div><div>The development of a direct compression excipient with extended-release property is crucial for improving tablet manufacturing and drug delivery. This research focuses on developing a novel co-processed excipient composed of rice starch (RS), methylcellulose (MC), and colloidal silicon dioxide (CSD) using a wet granulation technique. The ratios of RS: MC (1.66:1–1:3) and CSD concentrations (1.0 – 8.26 %) on the properties of co-processed material were evaluated. The RS co-processed with MC and CS (RMSs) formed agglomerate particles (199 – 294 μm of average particle size) with irregular shapes and rough surfaces due to the wet granulation technique. FT-IR spectroscopy confirmed that there was no change in the chemical structure during co-processing, while the amorphous characteristic of MC considerably decreased the crystallinity of the RMSs. The increase in the particle size and the bulk density of the RMSs improved material flowability (17 – 18° for angle of repose) and facilitated particle rearrangement during die filling. RS plasticity promoted material compressibility, while the brittleness of CSD contributed to the increased tablet tensile strength. The elastic recovery of RMSs relied on the ratio of RS, which facilitated permanent bonding, whereas incorporating CSD reduced the lubricant sensitivity of material. The co-processing with MC significantly improved material swellability and effectively maintained the polymer matrix for a long period in media with pH 1.2, 4.5, and 7.5. The <em>in vitro</em> release study confirmed the ability of RMSs to prolong drug release from the matrix tablets, where the cumulative drug release of RMS-2 tablets met the specification and conformed with Higuchi model. Among the RMSs, RMS-2 (RS co-processed with 48.7 % MC and 2.68 % CSD) exhibited the optimal ratio of co-processing, as it demonstrated more favorable compression behavior and extended-release property than other RMSs. These findings indicated that RMSs could potentially be used as a direct compression excipient with extended-release properties.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"208 ","pages":"Article 114623"},"PeriodicalIF":4.4,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-26DOI: 10.1016/j.ejpb.2025.114652
Agnieszka Wiesner , Paweł Zagrodzki , Alicja Gawalska , Monika Marcinkowska , Agnieszka Cios , Paweł Paśko
Background
Given the challenges of pediatric antibacterial therapy, it is crucial to formulate antibiotics with a lower potential for interaction with dietary interventions and tailor them for optimal administration in children. Chemometric methods allow us to analyze multiple interrelated variables simultaneously and uncover correlations.
Aim
We applied a chemometric approach to examine how food, beverages, antacids, and mineral supplements affect antibiotic bioavailability in adults and children, aiming to explore relationships between antibiotic structure, physicochemical properties, and post-meal changes in pharmacokinetic (PK) parameters.
Methods
We selected 95 antibacterial drugs for analysis, including beta-lactams (32), quinolones (25), macrolides (13), tetracyclines (16), and others (9). The input dataset comprised information from published clinical trials, chemical records, and calculations. We constructed hierarchical partial least squares (PLS) models with changes in PK parameters (ΔAUC, ΔCmax, ΔTmax, and Δ t ½) as response parameters and nine groups of molecular descriptors (M1-M9) as predictor parameters. We performed analyses separately in children and adults for different dietary interventions.
Results
In the final 10 PLS models, significant components explained 61–90% and 10.3–54.4% of the variance in the predictor and response parameter sets, respectively. We obtained 59 significant positive and negative correlations between antibiotic structure or physicochemical properties (molecular descriptors) and action in the human body in the presence of food, antacids, or mineral supplements (changes in PK parameters), of which 41 concern pediatric patients.
Conclusions
Chemometric methods can be helpful and valuable in investigating the interactions between antibiotics and dietary interventions. Using chemometrics may pave the way for formulating antibiotics for children with a lower potential to interact with food.
{"title":"Navigating through chemometrics: Unveiling antibiotic-food interactions for improved pediatric formulations ahead","authors":"Agnieszka Wiesner , Paweł Zagrodzki , Alicja Gawalska , Monika Marcinkowska , Agnieszka Cios , Paweł Paśko","doi":"10.1016/j.ejpb.2025.114652","DOIUrl":"10.1016/j.ejpb.2025.114652","url":null,"abstract":"<div><h3>Background</h3><div>Given the challenges of pediatric antibacterial therapy, it is crucial to formulate antibiotics with a lower potential for interaction with dietary interventions and tailor them for optimal administration in children. Chemometric methods allow us to analyze multiple interrelated variables simultaneously and uncover correlations.</div></div><div><h3>Aim</h3><div>We applied a chemometric approach to examine how food, beverages, antacids, and mineral supplements affect antibiotic bioavailability in adults and children, aiming to explore relationships between antibiotic structure, physicochemical properties, and post-meal changes in pharmacokinetic (PK) parameters.</div></div><div><h3>Methods</h3><div>We selected 95 antibacterial drugs for analysis, including beta-lactams (32), quinolones (25), macrolides (13), tetracyclines (16), and others (9). The input dataset comprised information from published clinical trials, chemical records, and calculations. We constructed hierarchical partial least squares (PLS) models with changes in PK parameters (ΔAUC, ΔC<sub>max</sub>, ΔT<sub>max</sub>, and Δ t ½) as response parameters and nine groups of molecular descriptors (M1-M9) as predictor parameters. We performed analyses separately in children and adults for different dietary interventions.</div></div><div><h3>Results</h3><div>In the final 10 PLS models, significant components explained 61–90% and 10.3–54.4% of the variance in the predictor and response parameter sets, respectively. We obtained 59 significant positive and negative correlations between antibiotic structure or physicochemical properties (molecular descriptors) and action in the human body in the presence of food, antacids, or mineral supplements (changes in PK parameters), of which 41 concern pediatric patients.</div></div><div><h3>Conclusions</h3><div>Chemometric methods can be helpful and valuable in investigating the interactions between antibiotics and dietary interventions. Using chemometrics may pave the way for formulating antibiotics for children with a lower potential to interact with food.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"208 ","pages":"Article 114652"},"PeriodicalIF":4.4,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-25DOI: 10.1016/j.ejpb.2025.114651
Nils Christian Böck , Julius Sundermann , Mirko Koziolek , Benjamin-Luca Keller , Karsten Mäder
Nanocrystalline formulations typically contain stabilizing additives to minimize the risk of particle growth or agglomeration. This risk is particularly relevant when the nanosuspension is converted into a solid drug product as the original state of the nanosuspension should be restored upon redispersion of the drug product in vivo. In this work, the behavior of different nonionic and anionic surfactants in solid nanocrystalline formulations and their effects on redispersibility under biorelevant conditions were investigated. For this purpose, nanocrystalline formulations of basic (itraconazole, ritonavir), acidic (naproxen), and neutral (fenofibrate) API containing nonionic polymers acting as steric stabilizers combined either with anionic (sodium dodecyl sulfate, deoxycholate sodium, docusate sodium) or non-ionic surfactants (polysorbate 80, vitamin E-TPGS) were manufactured by nano-milling. These formulations were turned into a solid drug product by lyophilization and their redispersibility was tested by dispersing them in biorelevant media with different pH values and by characterizing their particle size distribution (PSD) and surface charge. In the absence of an anionic surfactant, it was difficult to achieve particle sizes below 500 nm. However, formulations stabilized anionically were at risk of agglomeration in gastric media. For basic API, the agglomeration was reversible for formulations containing sodium deoxycholate after increasing the pH from acidic to neutral levels, but it was found to be irreversible for those containing sodium dodecyl sulfate and docusate sodium. In summary, the type of anionic stabilizer and its interplay with the physicochemical properties of the API (basic, acidic, or neutral) should be considered in the development of solid nanocrystal formulations.
{"title":"Impact of stabilizers on particle size and dispersion behavior in biorelevant media in solid nanocrystal formulations","authors":"Nils Christian Böck , Julius Sundermann , Mirko Koziolek , Benjamin-Luca Keller , Karsten Mäder","doi":"10.1016/j.ejpb.2025.114651","DOIUrl":"10.1016/j.ejpb.2025.114651","url":null,"abstract":"<div><div>Nanocrystalline formulations typically contain stabilizing additives to minimize the risk of particle growth or agglomeration. This risk is particularly relevant when the nanosuspension is converted into a solid drug product as the original state of the nanosuspension should be restored upon redispersion of the drug product <em>in vivo</em>. In this work, the behavior of different nonionic and anionic surfactants in solid nanocrystalline formulations and their effects on redispersibility under biorelevant conditions were investigated. For this purpose, nanocrystalline formulations of basic (itraconazole, ritonavir), acidic (naproxen), and neutral (fenofibrate) API containing nonionic polymers acting as steric stabilizers combined either with anionic (sodium dodecyl sulfate, deoxycholate sodium, docusate sodium) or non-ionic surfactants (polysorbate 80, vitamin E-TPGS) were manufactured by nano-milling. These formulations were turned into a solid drug product by lyophilization and their redispersibility was tested by dispersing them in biorelevant media with different pH values and by characterizing their particle size distribution (PSD) and surface charge. In the absence of an anionic surfactant, it was difficult to achieve particle sizes below 500 nm. However, formulations stabilized anionically were at risk of agglomeration in gastric media. For basic API, the agglomeration was reversible for formulations containing sodium deoxycholate after increasing the pH from acidic to neutral levels, but it was found to be irreversible for those containing sodium dodecyl sulfate and docusate sodium. In summary, the type of anionic stabilizer and its interplay with the physicochemical properties of the API (basic, acidic, or neutral) should be considered in the development of solid nanocrystal formulations.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"208 ","pages":"Article 114651"},"PeriodicalIF":4.4,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-25DOI: 10.1016/j.ejpb.2025.114650
Lanlan Song , Huihui Ye , Zhanghang Lv , Yichen Liu , Ziyi Lu , Jun Chen , Haofeng Pan , Luqiong Cai , Yuxin Chen , Shiqing Huang , Xingjie Zan , Xiaoying Huang , Chang Yu
Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) represents a spectrum of potentially fatal conditions that currently lack effective drug treatment. Recent researches suggest that Fibroblast Growth Factor 21 (FGF21) may protect against ALI/ARDS. However, the clinical use of FGF21 is limited by its rapid degradation, restricted targeting capabilities, and numerous adverse effects. Addressing this challenge, the study employs a pH-responsive nanoparticle delivery system known as Hexahistidine-metal Assembly (HmA) for administering FGF21. The entrapment efficiency (EE%) and loading capacity (LCwt%) of HmA exceed 90 % and 35 %, respectively, while the HmA@FGF21 nanoparticles exhibit an average size of 130 nm, a PDI value of approximately 0.28, and a zeta potential of 24 mV. In animal experiments, HmA@FGF21 administered in lipopolysaccharide (LPS)-induced lung injury significantly exceed those of standalone FGF21, including mitigating the pathological manifestations and reducing the wet/dry ratio, total protein concentration, and overall cell count in BALF of ALI, whether administered via the airway or intravenously. This therapeutic approach therefore shows promise for precise delivery of FGF21 to the lungs to treat ALI, and may offer a novel, and efficient method for delivery of potential pharmacological agents to address other lung diseases.
{"title":"Hexahistidine-metal assembly encapsulated fibroblast growth factor 21 for lipopolysaccharide-induced acute lung injury","authors":"Lanlan Song , Huihui Ye , Zhanghang Lv , Yichen Liu , Ziyi Lu , Jun Chen , Haofeng Pan , Luqiong Cai , Yuxin Chen , Shiqing Huang , Xingjie Zan , Xiaoying Huang , Chang Yu","doi":"10.1016/j.ejpb.2025.114650","DOIUrl":"10.1016/j.ejpb.2025.114650","url":null,"abstract":"<div><div>Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) represents a spectrum of potentially fatal conditions that currently lack effective drug treatment. Recent researches suggest that Fibroblast Growth Factor 21 (FGF21) may protect against ALI/ARDS. However, the clinical use of FGF21 is limited by its rapid degradation, restricted targeting capabilities, and numerous adverse effects. Addressing this challenge, the study employs a pH-responsive nanoparticle delivery system known as Hexahistidine-metal Assembly (HmA) for administering FGF21. The entrapment efficiency (EE%) and loading capacity (LCwt%) of HmA exceed 90 % and 35 %, respectively, while the HmA@FGF21 nanoparticles exhibit an average size of 130 nm, a PDI value of approximately 0.28, and a zeta potential of 24 mV. In animal experiments, HmA@FGF21 administered in lipopolysaccharide (LPS)-induced lung injury significantly exceed those of standalone FGF21, including mitigating the pathological manifestations and reducing the wet/dry ratio, total protein concentration, and overall cell count in BALF of ALI, whether administered via the airway or intravenously. This therapeutic approach therefore shows promise for precise delivery of FGF21 to the lungs to treat ALI, and may offer a novel, and efficient method for delivery of potential pharmacological agents to address other lung diseases.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"208 ","pages":"Article 114650"},"PeriodicalIF":4.4,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-22DOI: 10.1016/j.ejpb.2025.114635
Shubhashis Datta , Juraj Kronek , Zuzana Nadova , Ludmila Timulakova , Alzbeta Minarcikova , Pavol Miskovsky
Due to the straightforward single-step synthesis, amphiphilic gradient copoly(2-oxazoline)s are becoming more popular alternative to their block analogue for the development of next-generation drug delivery systems. Here, we investigated the influence of polymer architecture on the physiochemical and biological assessment of nanoformulations formed by the self-assembly of gradient copoly(2-oxazoline)s. Two different architectures were synthesized: hydrophilic-grad-hydrophobic (mono-gradient) and hydrophobic-grad-hydrophilic-grad-hydrophobic (di-gradient) which contained a hydrophilic monomer, 2-ethyl-2-oxazoline (EtOx) and a hydrophobic monomer, 2-phenyl-2-oxazoline (PhOx). Di-gradient copolymers self-assembled in the presence of a hydrophobic model drug, curcumin and formed monodispersed or slightly polydispersed nanoparticle solution. On the other hand, mono-gradient copolymers formed polydispersed nanoparticle solutions. Di-gradient copolymer was slightly more efficient to solubilize curcumin. Mono-gradient copolymer nanoparticle showed faster monomer chain exchange kinetics and comparatively less stability in the presence of serum albumin. At longer incubation times, faster drug release was observed from the mono-gradient copolymer nanoformulations. Cytotoxicity of free curcumin and curcumin loaded nanoparticles in cancer cell of U87 MG (human glioblastoma cell) was dose and time-dependent, whereby the significant cell death occurred after 48 h. Curcumin-loaded mono-gradient copolymer nanoparticles inhibited U87MG cancel cell growth to a large extent compared to the di-gradient copolymer nanoparticles.
{"title":"Effect of polymer architecture on the properties and in vitro cytotoxicity of drug formulation: A case study with mono- and di-gradient amphiphilic poly(2-Oxazoline)s","authors":"Shubhashis Datta , Juraj Kronek , Zuzana Nadova , Ludmila Timulakova , Alzbeta Minarcikova , Pavol Miskovsky","doi":"10.1016/j.ejpb.2025.114635","DOIUrl":"10.1016/j.ejpb.2025.114635","url":null,"abstract":"<div><div>Due to the straightforward single-step synthesis, amphiphilic gradient copoly(2-oxazoline)s are becoming more popular alternative to their block analogue for the development of next-generation drug delivery systems. Here, we investigated the influence of polymer architecture on the physiochemical and biological assessment of nanoformulations formed by the self-assembly of gradient copoly(2-oxazoline)s. Two different architectures were synthesized: hydrophilic-grad-hydrophobic (mono-gradient) and hydrophobic-grad-hydrophilic-grad-hydrophobic (di-gradient) which contained a hydrophilic monomer, 2-ethyl-2-oxazoline (EtOx) and a hydrophobic monomer, 2-phenyl-2-oxazoline (PhOx). Di-gradient copolymers self-assembled in the presence of a hydrophobic model drug, curcumin and formed monodispersed or slightly polydispersed nanoparticle solution. On the other hand, mono-gradient copolymers formed polydispersed nanoparticle solutions. Di-gradient copolymer was slightly more efficient to solubilize curcumin. Mono-gradient copolymer nanoparticle showed faster monomer chain exchange kinetics and comparatively less stability in the presence of serum albumin. At longer incubation times, faster drug release was observed from the mono-gradient copolymer nanoformulations. Cytotoxicity of free curcumin and curcumin loaded nanoparticles in cancer cell of U87 MG (human glioblastoma cell) was dose and time-dependent, whereby the significant cell death occurred after 48 h. Curcumin-loaded mono-gradient copolymer nanoparticles inhibited U87MG cancel cell growth to a large extent compared to the di-gradient copolymer nanoparticles.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"208 ","pages":"Article 114635"},"PeriodicalIF":4.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143037654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-22DOI: 10.1016/j.ejpb.2025.114636
Haja Muhamad , Abdul Basit Bashir , James Charlton-Harrison , Rand Abdulhussain , Nihad Mawla , Krishan Patel , James Williamson , Liam Blunt , Karl Walton , Barbara Conway , Kofi Asare-Addo
Recent developments in pharmacogenetics have emphasised the importance of customised medication, driving interest in technologies like FDM 3D-printing for tailored drug delivery. FDM 3D-printing is a promising technique for the on-demand manufacturing of customised oral dosage forms, providing flexibility in terms of shape and size, dose and drug release profiles. This study investigates the fabrication and characterisation of 3D-printed oral dosage forms using PEO as the primary polymer and PEG 6 K as a plasticiser. Firstly, the printability of the PEO filaments with different propranolol hydrochloride concentrations was explored using the hot-melt extrusion technology. The influence of the propranolol hydrochloride concentrations on the mechanical properties of the filaments was examined was then examined after which surface characteristics, including roughness and wettability, were evaluated. Dissolution imaging was used to visualise the effects of drug content on the swelling and dissolution characteristics of the PEO-based 3D-printed tablets. Results showed a reduction in the flexural stress of the filaments with increasing drug load. It was also observed that increasing the drug load led to higher surface roughness and lower contact angles of the 3D-printed PEO tablets, implying increased surface hydrophilicity. The swelling behaviour of the tablets increased with higher drug concentrations, resulting in a larger gel layer formation. When comparing the drug release percentages, the release rate was higher in the 10 mg propranolol tablets, suggesting that a lower drug content led to a faster release. The greater gel layer of the 40 mg PPN tablets hindered the drug release by acting as a diffusion barrier, while the 10 mg PPN tablets, with less swelling and gel formation, experienced a faster drug release. These findings show the importance of drug content in modifying the surface properties, swelling behaviour, and drug release profiles of 3D-printed PEO tablets. The study also demonstrates the novel use of dissolution imaging for 3D-printed dosage forms, providing valuable quantitative and qualitative insights into swelling dynamics and channel formation to optimise 3D-printed tablets for drug delivery systems.
{"title":"Hot-melt extruded-FDM 3D-printed polyethylene oxide tablets: Dissolution imaging analysis of swelling and drug release","authors":"Haja Muhamad , Abdul Basit Bashir , James Charlton-Harrison , Rand Abdulhussain , Nihad Mawla , Krishan Patel , James Williamson , Liam Blunt , Karl Walton , Barbara Conway , Kofi Asare-Addo","doi":"10.1016/j.ejpb.2025.114636","DOIUrl":"10.1016/j.ejpb.2025.114636","url":null,"abstract":"<div><div>Recent developments in pharmacogenetics have emphasised the importance of customised medication, driving interest in technologies like FDM 3D-printing for tailored drug delivery. FDM 3D-printing is a promising technique for the on-demand manufacturing of customised oral dosage forms, providing flexibility in terms of shape and size, dose and drug release profiles. This study investigates the fabrication and characterisation of 3D-printed oral dosage forms using PEO as the primary polymer and PEG 6 K as a plasticiser. Firstly, the printability of the PEO filaments with different propranolol hydrochloride concentrations was explored using the hot-melt extrusion technology. The influence of the propranolol hydrochloride concentrations on the mechanical properties of the filaments was examined was then examined after which surface characteristics, including roughness and wettability, were evaluated. Dissolution imaging was used to visualise the effects of drug content on the swelling and dissolution characteristics of the PEO-based 3D-printed tablets. Results showed a reduction in the flexural stress of the filaments with increasing drug load. It was also observed that increasing the drug load led to higher surface roughness and lower contact angles of the 3D-printed PEO tablets, implying increased surface hydrophilicity. The swelling behaviour of the tablets increased with higher drug concentrations, resulting in a larger gel layer formation. When comparing the drug release percentages, the release rate was higher in the 10 mg propranolol tablets, suggesting that a lower drug content led to a faster release. The greater gel layer of the 40 mg PPN tablets hindered the drug release by acting as a diffusion barrier, while the 10 mg PPN tablets, with less swelling and gel formation, experienced a faster drug release. These findings show the importance of drug content in modifying the surface properties, swelling behaviour, and drug release profiles of 3D-printed PEO tablets. The study also demonstrates the novel use of dissolution imaging for 3D-printed dosage forms, providing valuable quantitative and qualitative insights into swelling dynamics and channel formation to optimise 3D-printed tablets for drug delivery systems.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"208 ","pages":"Article 114636"},"PeriodicalIF":4.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143037667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-19DOI: 10.1016/j.ejpb.2025.114632
S. İrem Güler , Cem Levent Altan , E. Esma Demircioglu , Nihan Verimli , Beyza Abisoglu , Cigdem Bayraktaroglu , Mustafa Caglar Beker , S. Sibel Erdem
Late diagnosis is one of the major obstacles for the treatment of breast cancer which can be overcome with a system offering sensitive imaging and selective therapeutic effect. In this study, we developed a “dark-bright” multifunctional drug delivery system bringing real-time imaging and non-invasive therapy together. Theranostic ability of the system was delivered by Verteporfin (VP), serving as a fluorescence probe and a photosensitizer. To create a “dark state” system via self-quenching ability of VP, it was immobilized onto the superparamagnetic iron oxide nanoparticle (SPION) surface. Upon cellular uptake of the “dark state” system, release of VP led to fluorescence regain, switching the system to “bright state” after which photodynamic therapy (PDT) was initiated to lead to cell death. Theranostic feature of the system was evaluated in MCF-7 and MDA-MB-231 cell lines. Following internalization, fluorescence signal was increased up to ∼56-fold in MCF-7 cells. The IC50 value decreased ∼20-fold and ∼117-fold in MCF-7 and MDA-MB-231 cell lines, respectively. Moreover, the system significantly inhibited migration in the highly aggressive MDA-MB-231 cell line and induced apoptosis by caspase-3 activation. The developed “dark-bright” system is a promising multifunctional drug delivery vehicle with extraordinary theranostic features for the detection and destruction of micro tumors.
{"title":"Glow in the dark tumor: Enhanced near-IR visualization and destruction of cancer with a self-quenched theranostic","authors":"S. İrem Güler , Cem Levent Altan , E. Esma Demircioglu , Nihan Verimli , Beyza Abisoglu , Cigdem Bayraktaroglu , Mustafa Caglar Beker , S. Sibel Erdem","doi":"10.1016/j.ejpb.2025.114632","DOIUrl":"10.1016/j.ejpb.2025.114632","url":null,"abstract":"<div><div>Late diagnosis is one of the major obstacles for the treatment of breast cancer which can be overcome with a system offering sensitive imaging and selective therapeutic effect. In this study, we developed a “dark-bright” multifunctional drug delivery system bringing real-time imaging and non-invasive therapy together. Theranostic ability of the system was delivered by Verteporfin (VP), serving as a fluorescence probe and a photosensitizer. To create a “dark state” system via self-quenching ability of VP, it was immobilized onto the superparamagnetic iron oxide nanoparticle (SPION) surface. Upon cellular uptake of the “dark state” system, release of VP led to fluorescence regain, switching the system to “bright state” after which photodynamic therapy (PDT) was initiated to lead to cell death. Theranostic feature of the system was evaluated in MCF-7 and MDA-MB-231 cell lines. Following internalization, fluorescence signal was increased up to ∼56-fold in MCF-7 cells. The IC<sub>50</sub> value decreased ∼20-fold and ∼117-fold in MCF-7 and MDA-MB-231 cell lines, respectively. Moreover, the system significantly inhibited migration in the highly aggressive MDA-MB-231 cell line and induced apoptosis by caspase-3 activation. The developed “dark-bright” system is a promising multifunctional drug delivery vehicle with extraordinary theranostic features for the detection and destruction of micro tumors.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"208 ","pages":"Article 114632"},"PeriodicalIF":4.4,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pharmaceutical excipients, commonly known as inactive ingredients, encompass any substance aside from the active ingredient that fulfills a distinct and vital role in a formulation. Their purpose is to enhance specific characteristics, whether associated with the performance of the formulation or aspects related to patient comfort, safety, and acceptability. Because of the limited toxicity studies provided, and the several allergic and toxic side effects that have been reported throughout the years, it is not trivial for the regulatory agencies to approve inactive ingredients for human use. In general, excipients are approved within good manufacturing practices (GMPs) when they undergo analysis of the formulation as a whole, not the standalone substance. However, there is a lack of updated information regarding this subject, given that only the American Food and Drug Administration (FDA) provides a complete list describing the inactive ingredients that are currently approved in drug products for human use. Here, we aimed to provide an overview of key excipients approved by the FDA for ophthalmic use in humans, focusing on their functional roles in ophthalmic formulations, particularly eye drops, and the regulatory requirements involved in these ingredients approval.
{"title":"Excipients in drug delivery systems: A comprehensive review of approved inactive ingredients for human ophthalmic formulations","authors":"Raquel Gregorio Arribada , Daniela Rodrigues-Braz , Armando Silva-Cunha , Francine Behar-Cohen","doi":"10.1016/j.ejpb.2025.114637","DOIUrl":"10.1016/j.ejpb.2025.114637","url":null,"abstract":"<div><div>Pharmaceutical excipients, commonly known as inactive ingredients, encompass any substance aside from the active ingredient that fulfills a distinct and vital role in a formulation. Their purpose is to enhance specific characteristics, whether associated with the performance of the formulation or aspects related to patient comfort, safety, and acceptability. Because of the limited toxicity studies provided, and the several allergic and toxic side effects that have been reported throughout the years, it is not trivial for the regulatory agencies to approve inactive ingredients for human use. In general, excipients are approved within good manufacturing practices (GMPs) when they undergo analysis of the formulation as a whole, not the standalone substance. However, there is a lack of updated information regarding this subject, given that only the American Food and Drug Administration (FDA) provides a complete list describing the inactive ingredients that are currently approved in drug products for human use. Here, we aimed to provide an overview of key excipients approved by the FDA for ophthalmic use in humans, focusing on their functional roles in ophthalmic formulations, particularly eye drops, and the regulatory requirements involved in these ingredients approval.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"208 ","pages":"Article 114637"},"PeriodicalIF":4.4,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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