European Journal of Pharmaceutical Sciences最新文献

{"title":"Optimising electronic documentation of medication in Hungary: Itemised, complete, historical, and standardised event recording","authors":"Edina Hornung ,&nbsp;Zelma Faisal ,&nbsp;László Técsi ,&nbsp;Andrea Lovász ,&nbsp;Tamás Dóczi ,&nbsp;Lajos Botz","doi":"10.1016/j.ejps.2025.107079","DOIUrl":"10.1016/j.ejps.2025.107079","url":null,"abstract":"<div><div>Hospital care is a highly complex process, requiring comprehensive documentation of all aspects of the patient journey in electronic health records. A critical component of this care is the accurate tracking of patient medications. International standards are not consistently incorporated into the electronic medication systems currently in use worldwide, and their interoperability remains an unresolved issue. We recognised the need to develop a set of standardised data elements that ensure consistent and accurate documentation. Although the medication systems studied exhibit various strengths and weaknesses and can satisfactorily document certain aspects of the medication process, none achieve the necessary level of optimal documentation. Our paper presents a new perspective on medication recording by identifying the electronic data requirements for all events in an itemized, complete, historical, and standardized manner. To address this gap, we collected, defined, and introduced the essential data elements required for the comprehensive documentation of medication sub-processes for the first time in our study. The Fast Health Interoperability Resources (FHIR) data exchange standard was employed for designing these data requirements. Our research identified and categorised 138 data elements essential for describing the complete medication process, including medication description, requests, dispensation, and administration. These data elements were divided into fundamental and supplementary categories. We developed a survey form to assess medication systems. In a pilot study, we tested the quality of 5 medication systems, currently in operation in Hungary. Our analysis assessed the accuracy of the electronic recording of medication and the correspondence of the recorded data elements with international standards. None of the systems demonstrated the ability to document medication accurately or capture all fundamental data elements. The best-performing system managed to record 63 % of all fundamental data elements, while the worst-performing system managed only to document 30 %. The names and the values of data elements in these systems did not comply with international standards either. The primary clinical pharmaceutical usefulness of this study was to enhance the digital documentation of medication in hospitals to meet comprehensive data recording requirements, ensure greater compliance, and improve their suitability for enriching clinical health data files, enabling real-world studies, pharmacovigilance analyses, and the identification of drug repositioning opportunities.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"209 ","pages":"Article 107079"},"PeriodicalIF":4.3,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771851","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}

{"title":"Discovery of STING antagonists targeting cGAS-STING pathway to alleviate IMQ-induced psoriasis-like dermatitis","authors":"Zhixiong Zhang ,&nbsp;Xian Wei ,&nbsp;Qiang Huang ,&nbsp;Zhonghua Shi ,&nbsp;Xiaofeng Chen ,&nbsp;Jialin Wu ,&nbsp;Xin Wang ,&nbsp;Jiaqi Li ,&nbsp;Lantu Gou ,&nbsp;Jinliang Yang","doi":"10.1016/j.ejps.2025.107091","DOIUrl":"10.1016/j.ejps.2025.107091","url":null,"abstract":"<div><div>The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway is pivotal in the immune defense against infections and cancer. However, aberrant activation of this pathway can trigger autoimmune and inflammatory diseases by inducing excessive production of type I interferon (IFN) and pro-inflammatory cytokines. Inhibition of the aberrant activation of the cGAS-STING signaling pathway by targeting STING represents a novel therapeutic strategy for these autoimmune and inflammatory disorders. In this study, we discovered three novel STING antagonists based on surface plasmon resonance (SPR), differential scanning fluorimetry (DSF), and ISRE (interferon stimulated response element)-luciferase assays. The efficacy and pharmacological mechanisms of the three STING antagonists for treating imiquimod (IMQ)-induced psoriasis-like dermatitis by western blotting (WB), flow fluorescence, and immunostaining. The three STING antagonists exhibited pan-inhibitory activities on the activation of both the human and mouse cGAS-STING signaling pathway. Intravenous and topical administration of the three antagonists alleviated the inflammation and skin lesions associated with IMQ-induced psoriasis-like dermatitis via suppression of the inflammatory cascade mediated by the IMQ-TLR-7-NF-κB/cGAS-STING-NF-κB/IL-1β-IL-1R-NF-κB/TNFα-TNF-R-NF-κB signaling axis. In conclusion, we identified three novel STING antagonists with pan-inhibitory activities against human and mouse STING, providing lead compounds for the future development of both STING antagonists and immune agents for therapeutically manipulating STING-driven diseases, such as psoriasis. Our findings offer another new therapeutic strategy for managing STING-driven autoimmune and inflammatory diseases, while also reemphasizing the critical role of the cGAS-STING signaling pathway in such conditions.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"210 ","pages":"Article 107091"},"PeriodicalIF":4.3,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771738","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}

{"title":"Response to the commentary on “are all measures of liver Kpuu a function of FH, as determined following oral dosing, or have we made a critical error in defining hepatic drug clearance?”","authors":"Leslie Z. Benet,&nbsp;Jasleen K. Sodhi","doi":"10.1016/j.ejps.2025.107088","DOIUrl":"10.1016/j.ejps.2025.107088","url":null,"abstract":"<div><div>Recently, Sugano commented on our above-titled publication stating that he was a reviewer for the paper. In the Acknowledgements, Sugano indicated that we “kindly suggested publishing the reviewer report as an article”. What we had actually written was: “prior to accepting the [unidentified] reviewer's approach, however, we believe he/she would have to publish a paper justifying the methodology and proposing how <em>in vivo</em> clinical data could be analyzed with such methodology”. We further explained the fallacy of the accepted mechanistic models of hepatic elimination in a subsequent manuscript titled “Pharmacokinetic theory must consider published experimental data”, published online a month after the Sugano commentary became available –not in time for the author to review the full explanation before his commentary was published. Our above-titled publication makes no assumptions or discussions regarding how <em>Kp_uu</em> should be measured, the major topic of the Sugano paper. Here we detail why the commentary methodology is not relevant to our demonstration that the present mechanistic models of hepatic elimination all lead to the unlikely conclusion that <em>Kp_uu</em> cannot exceed unity and is related to <em>F_H</em>. We also detail why the Extended Clearance Model should not be used for <em>in vitro</em>-<em>in vivo</em> extrapolation.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"209 ","pages":"Article 107088"},"PeriodicalIF":4.3,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771852","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}

{"title":"Engineered-affibody conjugates contribute to the specific targeting and cellular retention of polyplexes in Erbb3 overexpressed lung cancer cells","authors":"Siyu Chen ,&nbsp;Anny Nguyen ,&nbsp;Joschka T. Müller ,&nbsp;Müge Molbay ,&nbsp;Aditi Mehta ,&nbsp;Sahana Sheshachala ,&nbsp;Kemal Baskaya ,&nbsp;Nathan Adams ,&nbsp;Simone Pinto Carneiro ,&nbsp;Olivia M. Merkel","doi":"10.1016/j.ejps.2025.107090","DOIUrl":"10.1016/j.ejps.2025.107090","url":null,"abstract":"<div><div>Ligand-modified nanoparticles have shown the ability to specifically bind to tumor cells, improving retention in tumors after initial accumulation driven by the enhanced permeability and retention effect. These particles are typically engineered to bind to receptors overexpressed in cancer cells compared to healthy cells, such as the HER3 (Erbb3) receptor in lung cancer. In this study, we confirmed the overexpression of Erbb3 in various <em>KRAS</em> mutant lung cancer cell lines. An engineered affibody, well-established in previous research, was selected to target Erbb3 as a proof of concept. The affibody was integrated into the particle system via two distinct strategies. In the pre-functionalization approach, the affibody was conjugated to PEI or C14-PEI using SPDP as a linker. A spectral shift technique was then used to assess the affinity of the affibody and affibody conjugates toward Erbb3, allowing us to estimate the half-maximal effective concentration (EC<em>₅₀</em>). Following synthesis and characterization, various polyplex formulations were prepared, including mRNA complexes with PEI-affibody, C14-PEI/PEI-affibody, and C14-PEI/C14-PEI-affibody. In the post-functionalization approach, polyplex formulations composed of different blends of C14-PEI and functionalized Azido-PEI were initially prepared and subsequently modified with DBCO-functionalized affibody via click chemistry. These formulations were prepared at various nitrogen to phosphate (N/P) ratios and characterized in terms of particle size, polydispersity index (PDI), and zeta potential. We also evaluated cellular uptake and eGFP mRNA expression to understand how the different formulations and conjugates influenced ligand-modified polyplex properties and delivery behavior. Our results demonstrated that affibody conjugates can specifically target Erbb3 and promote polyplex accumulation in <em>KRAS</em>-mutated lung cancer cells. We further analyzed the impact of conjugation methods and affibody density on polyplex design and performance. In conclusion, this study highlights the advantages of using specific targeting ligands. By optimizing formulation components, conjugation methods, and ligand density, various targeting ligands can be attached to polyplexes, enhancing cell-specific targeting, internalization, and retention. These findings provide valuable insights and a foundation for future targeted therapies and polyplex design.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"209 ","pages":"Article 107090"},"PeriodicalIF":4.3,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating accumulation of budesonide and tacrolimus in an ex vivo porcine oesophageal model: Translational potential for local application of drugs to treat eosinophilic oesophagitis","authors":"Farhan Taherali ,&nbsp;Marissa Taub ,&nbsp;Felipe Varum ,&nbsp;Roberto Bravo ,&nbsp;Abdul W Basit","doi":"10.1016/j.ejps.2025.107086","DOIUrl":"10.1016/j.ejps.2025.107086","url":null,"abstract":"<div><div>Eosinophilic oesophagitis (EoE) is a chronic inflammatory disease afflicting the oesophagus and causing lifelong morbidity. Over the last few decades, EoE has significantly increased in prevalence with oral corticosteroids, such as budesonide, being the current mainstay of therapy. Tacrolimus is an immunomodulatory drug with anti-inflammation properties that is not on the conventional therapeutic regimen for EoE but offers a promising alternative non-steroidal treatment for patients who do not respond to diet elimination, proton pump inhibitors (PPIs), or corticosteroids. This study aims to investigate and compare the accumulation between locally delivered budesonide and tacrolimus, using an ex vivo porcine oesophageal model of EoE, over a range of contact times up to 30 min. Budesonide and tacrolimus were solubilised in a cosolvent and surfactant formulation to maintain solvation capacity in artificial saliva. Injured and non-injured (control) porcine oesophageal mucosa were used as surrogates to represent EoE and healthy oesophageal mucosa in humans, respectively, due to the highly similar physiological architecture of the oesophagus. EoE-mimicking oesophageal damage was chemically induced by pancreatic enzymes and bile salts known to dilate intercellular spaces typically observed in EoE pathophysiology where tight junction damage was represented by an irreversible drop in transepithelial electrical resistance (TEER). Whole tissue and basolateral accumulation of budesonide and tacrolimus were quantified after 30 min using liquid chromatography tandem mass spectrometry (LC-MS/MS). Tacrolimus yielded a significant increase (<em>p</em> &lt; 0.05) in injured tissue accumulation (approximately two-fold) in comparison to non-injured tissue, while budesonide yielded no significant difference (<em>p</em> &gt; 0.05) in tissue accumulation between the two. Considering the significant accumulation of tacrolimus in this ex vivo porcine model of EoE, using injury-induced porcine oesophageal mucosa, this study suggests the use of tacrolimus as a targeted local therapy for the treatment of EoE.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"209 ","pages":"Article 107086"},"PeriodicalIF":4.3,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quality assessment of cholic acid as an active pharmaceutical ingredient: Analytical method and results","authors":"Y. Polak ,&nbsp;C.E.M. Hollak ,&nbsp;E.L. Swart ,&nbsp;E.M. Kemper","doi":"10.1016/j.ejps.2025.107083","DOIUrl":"10.1016/j.ejps.2025.107083","url":null,"abstract":"<div><div>Commercial cholic acid (CA) treatment is currently unavailable to Dutch patients with a bile acid synthesis defect. CA treatment has been hypothesized to correct the biochemical abnormalities associated with these disorders and potentially slowing down disease progression. To address this need, the hospital pharmacy of Amsterdam University Medical Center developed CA capsules for use in a clinical trial in The Netherlands. Challenges arose during the quality control of CA active pharmaceutical ingredient (API) as no specific substance monograph is available in the European Pharmacopoeia or other effective pharmacopoeias. In this article, we share an analytical method validated for testing the purity of CA and present the results of its quality control, offering practical guidance for ensuring adequate quality control of CA.</div><div>Pharmaceutical quality tests were performed on four batches of CA following the guidance given in the European Pharmacopoeia general monograph on substances for pharmaceutical use. The results confirm the suitability of our analytical method for CA quality control and demonstrate that the CA meets the high-quality standards required for pharmaceutical use.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"209 ","pages":"Article 107083"},"PeriodicalIF":4.3,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and preclinical evaluation of a gallium-68 labeled novel diagnostic tracer for visualizing ALK expression in tumor","authors":"Zhen-Peng Yu ,&nbsp;Ke-Xin Sun ,&nbsp;Dan Zhang ,&nbsp;Zhi-Qiang Yu ,&nbsp;Deng-Yun Chen ,&nbsp;Hong Zhu ,&nbsp;Hongwei Si ,&nbsp;Peng-Fei Dai","doi":"10.1016/j.ejps.2025.107087","DOIUrl":"10.1016/j.ejps.2025.107087","url":null,"abstract":"<div><div>Anaplastic lymphoma kinase (ALK) is prominently expressed in numerous malignant tumors, which lead to aberrant tumor proliferation, invasion and metastasis. Ceritinib (LDK378), as second-generation targeted drugs, has been used to treat advanced ALK-positive non-small cell lung cancer (NSCLC). Herein, we sought to develop a novel ALK-positron emission tomography/magnetic resonance (PET/MR) tracer ⁶⁸Ga-DOTA-CTB (⁶⁸Ga labeled ceritinib) based on ceritinib scaffold to monitor the ALK expression levels during targeted therapy with ceritinib. The ⁶⁸Ga-DOTA-CTB radiotracer, obtained via a simple labeling procedure, exhibits favorable radiochemical purity, stability, and pharmacokinetic properties. Subsequently, cellular uptake experiments have demonstrated that ⁶⁸Ga-DOTA-CTB could be accumulated in H2228 cells. Imaging and biodistribution experiments have revealed significant uptake of the radiotracer in the tumors of the experimental group, while tumors in the blocking group, which were saturated with an excess of precursor, exhibited a markedly reduced level of radioactivity. These empirical findings suggest that ⁶⁸Ga-DOTA-CTB holds substantial potential as a novel PET/MR imaging tracer for ALK-positive tumors.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"209 ","pages":"Article 107087"},"PeriodicalIF":4.3,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breaking barriers: The novel in vitro microdialysis system enables reproducing in vivo extraction efficiencies of linezolid","authors":"Felix Leon Müller ,&nbsp;Davide Bindellini ,&nbsp;Gerd Mikus ,&nbsp;Robin Michelet ,&nbsp;Charlotte Kloft","doi":"10.1016/j.ejps.2025.107085","DOIUrl":"10.1016/j.ejps.2025.107085","url":null,"abstract":"<div><div>Reported extraction efficiencies (EE) of the minimally invasive microdialysis (µD) technique for linezolid (LIN) varied in subcutaneous adipose tissue of obese 42.8 % (95 %CI:35.9 %-50.2 %) and non-obese patients 61.0 % (95 %CI:54.4 %-67.1 %). EE must be determined <em>in vivo</em>, as <em>in vitro</em> µD systems (EE=94.1 % for LIN) so far fail to reflect <em>in vivo</em> processes and conditions. This study aimed to develop an <em>in vitro</em> µD system capable of reproducing <em>in vivo</em> EE of LIN for different populations by mimicking tissue characteristics and processes limiting EE. Based on the static <em>in vitro</em> µD system two novel systems were developed: (i) mimicking catheter surrounding as artificially tissue structure (aTS) by creating a porous matrix using milling beads, and (ii) adding a surrounding flow as artificial tissue perfusion (aTP) through the aTS. While experiments using the aTS µD system resulted in a low EE of 33.2 % (95 %CI=31.8 %-34.7 %), adding aTP increased EE in a function of aTP, to a maximum of 97.2 % (95 %CI=91.1 %-104 %). The aTP µD system successfully reproduced the median reported <em>in vivo</em> EE range for LIN, matching EE for obese and non-obese at an aTP of 0.013 and 0.061 mL/min, respectively. By reproducing <em>in vivo</em> EEs for LIN, the novel aTP µD system (aTPMS) provides a platform for optimising µD settings in clinical trials, with future studies needed to explore its application to other substances.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"209 ","pages":"Article 107085"},"PeriodicalIF":4.3,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751831","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}

{"title":"Racemic drugs are not necessarily less efficacious and less safe than their single-enantiomer components","authors":"Israel Agranat ,&nbsp;Ilaria D'Acquarica","doi":"10.1016/j.ejps.2025.107082","DOIUrl":"10.1016/j.ejps.2025.107082","url":null,"abstract":"<div><div>Practitioners of drug discovery and development of chiral drugs are confronted with the dilemma whether to develop a racemate or a single enantiomer. In 2024, articles were published stating that single enantiomers are clinically more potent than racemic mixtures and that the use of single enantiomers instead of racemates improves the effectiveness and/or safety of treatment. The <em>Commentary</em> provides a rebuttal of these allegations. A historical survey of the motivation for developing single-enantiomer drugs is given. Cases of preference of racemate/diastereomeric-mixture drugs over single-enantiomer drugs are described, along with the following cases of teaching away from chiral switches of racemate/diastereomeric-mixture drugs to single-enantiomer drugs: rapid interconversion <em>in vivo</em> of paired enantiomers, fast <em>in vivo</em> conversion of a diastereomeric-mixture drug to its active form, enantiomerization <em>in vivo</em> of an (<em>R</em>)-enantiomer to its paired (<em>S</em>)-enantiomer. Advantages of racemic drugs versus single-enantiomer drugs and <em>vice versa</em> are listed. Racemate/diastereomeric-mixture drugs are not necessarily less efficacious and less safe than their single-enantiomer components. They will continue to serve as potential candidates for chiral switches. The <em>Commentary</em> concludes with highlighting the proposition that development of chiral drugs should proceed forward with the racemate until and unless some relevant differentiated property is identified.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"209 ","pages":"Article 107082"},"PeriodicalIF":4.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742728","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}

{"title":"Co-milling of glass forming ability class III drugs: Comparing the impact of low and high glass transition temperatures","authors":"Nicolas Pätzmann ,&nbsp;Josef Beránek ,&nbsp;Brendan T. Griffin ,&nbsp;Martin Kuentz ,&nbsp;Patrick J. O'Dwyer","doi":"10.1016/j.ejps.2025.107081","DOIUrl":"10.1016/j.ejps.2025.107081","url":null,"abstract":"<div><div>With an increasing focus on sustainable technologies in the pharmaceutical industry, milling provides a solvent-free approach to improve drug dissolution. Milling of drugs with an excipient offers additional opportunities to achieve supersaturation kinetics. Therefore, this work aims to present insights of co-milling fenofibrate and apremilast, two good glass formers with low and high glass transition temperatures (T_gs) respectively. Drugs were co-milled with croscarmellose sodium for various process durations followed by thermal analysis, investigation of crystallinity, surface area and dissolution. The dissolution enhancement of the low-T_g glass former fenofibrate highly correlated with the process-induced increase in surface area of co-milled systems (R² = 0.96). In contrast, the high-T_g glass former apremilast lost its crystalline order gradually after ≥ 10 min of co-milling, and favourable supersaturation kinetics during biorelevant dissolution testing were observed. Interestingly, the melting point of co-milled apremilast decreased and linearly correlated with the highest measured drug concentration (c_max) during <em>in vitro</em> dissolution (onset temperature R² = 0.98; peak temperature R² = 0.96). The melting point depression remained stable after 90 days for apremilast, whereas fenofibrate co-milled for 20 min or more showed an increase in melting point upon storage. This study demonstrated that co-milling with croscarmellose sodium is ideally suited to good glass formers with a high T_g. The melting point depression is thereby proposed as an easily accessible critical quality attribute to estimate likely dissolution performance of drugs in dry co-milled formulations.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"209 ","pages":"Article 107081"},"PeriodicalIF":4.3,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}