European Journal of Pharmaceutical Sciences最新文献

{"title":"VA1213, a selective COX-2 inhibitor, exhibits antitumor activity by suppressing EGFR, AKT, and ERK1/2 phosphorylation","authors":"Valerio Ciccone ,&nbsp;Claudia Cecchin ,&nbsp;Maria Frosini ,&nbsp;Mario Saletti ,&nbsp;Samuele Maramai ,&nbsp;Germano Giuliani ,&nbsp;Marco Paolino ,&nbsp;Andrea Cappelli ,&nbsp;Maurizio Anzini ,&nbsp;Sandra Donnini ,&nbsp;Lucia Morbidelli","doi":"10.1016/j.ejps.2025.107422","DOIUrl":"10.1016/j.ejps.2025.107422","url":null,"abstract":"<div><div>Cyclooxygenase-2 (COX-2) is overexpressed in various cancers and has emerged as a promising target in oncological pharmacotherapy.</div><div>This study investigates the in vitro antitumor properties and mechanism of action of novel vicinal diaryl-substituted heterocyclic COX-2 inhibitors, with a focus on <strong>VA1213</strong>, in comparison to celecoxib, a widely marketed COX-2 inhibitor known for its off-target effects. We assessed cytotoxicity, apoptosis induction, cell-cycle distribution, antimetastatic activity, and alterations in key signaling pathways in HT-29 colorectal carcinoma and MDA-MB-231 breast carcinoma cell lines. Among the novel compounds, <strong>VA1213</strong> exhibited the most potent growth-inhibitory activity, demonstrating time-dependent cytotoxicity with a lower IC₅₀ after 48–72 h of treatment compared to <strong>VA692</strong> and <strong>VA694</strong>, and consistent with that observed for celecoxib.</div><div>Unlike celecoxib, which produced rapid cytotoxic effects, <strong>VA1213</strong> required prolonged exposure, suggesting a distinct mechanism of action. <strong>VA1213</strong> induced G₀/G₁ phase cell cycle arrest and apoptosis via caspase-3 activation. Furthermore, it impaired EGFR downstream signaling by reducing ERK1/2 and AKT phosphorylation, without directly inhibiting EGFR itself. At sub-cytotoxic concentrations, <strong>VA1213</strong> was more effective than celecoxib in inhibiting cell migration and demonstrated a comparable reduction in clonogenic potential. These findings highlight <strong>VA1213</strong> as a COX-2 inhibitor with noteworthy in vitro antitumor efficacy, comparable to that of celecoxib. Its ability to interfere with multiple cancer-associated signaling pathways and reduce tumor cell aggressiveness underscores its potential as a promising therapeutic candidate. Further in vivo studies are warranted to confirm its efficacy and assess potential off-target effects.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"219 ","pages":"Article 107422"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145818640","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":"Scoping review to identify data needs and environmental hotspots for future LCA Studies: Insights into pharmaceutical excipients and processes","authors":"Anja Autzen Virtanen ,&nbsp;Satu Lakio ,&nbsp;Atif Madi ,&nbsp;Mia Sivén","doi":"10.1016/j.ejps.2026.107453","DOIUrl":"10.1016/j.ejps.2026.107453","url":null,"abstract":"<div><div>In recent years, the environmental assessment and optimization of pharmaceutical dosage forms have received increasing attention. Consequently, interest in Life Cycle Assessments (LCA) has grown, and LCA is rapidly becoming the standard method of environmental evaluations across many industries, including the pharmaceutical sector. LCA is, however, a high entry barrier method requiring expertise, software- and database access, and process specific experimentally obtained performance data (e.g. electricity consumption). In the context of pharmaceuticals, significant challenges arise due to the limited availability of input data. Because of these limitations, we wanted to investigate the feasibility of using a scoping review as an alternative to LCA for evaluating the environmental implications of pharmaceuticals. In this literature review, a total of 8788 articles were screened, of which 117 were relevant. The search was anchored in a formulation previously developed. In this formulation, 3.0 mm minitablets were manufactured by direct compression from a spray-dried amorphous solid dispersion of indomethacin in polyvinylpyrrolidone (PVP) or hydroxypropyl methylcellulose acetate succinate (HPMCAS) with the additional use of milled lactose monohydrate (LACT), microcrystalline cellulose (MCC) and magnesium stearate (MgSt) as tablet excipients. Through the systematic literature review, relevant environmental information was found for most of the processes and excipients investigated. Research currently undertaken at the intersection of environmental review and pharmaceutical manufacturing shows an upward trend. Most notably, recent research indicates that excipients generally regarded as safe (GRAS) may not necessarily be without environmental concern. Furthermore, excipients may be manufactured through multiple different routes which muddles the environmental comparison of different options. Still, this literature review identified a marked absence of sustainability-themed research specific to pharmaceutical manufacturing. With the issues uncovered, more research is sorely needed to provide guidance in formulation choices.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"219 ","pages":"Article 107453"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146085218","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":"3D printed intrauterine device development containing dual anticancer drugs for the treatment of uterine cancer","authors":"Cem Varan ,&nbsp;Davut Aksüt ,&nbsp;Murat Şen ,&nbsp;Erem Bilensoy","doi":"10.1016/j.ejps.2026.107456","DOIUrl":"10.1016/j.ejps.2026.107456","url":null,"abstract":"<div><div>Uterine cancer is a major global health problem and treatment frequently includes invasive surgery that severely compromises fertility. Current systemic chemotherapeutic drugs, such as paclitaxel (PCX) and carboplatin (CBP), lack an established standard protocol and their efficacy is limited. This study focuses on the development of a personalized, local drug delivery system for the treatment of uterine cancer.</div><div>The intrauterine devices (IUDs) were prepared using polycaprolactone (PCL) filaments containing PCX and CBP complexed to cyclodextrin (CD) to enhance the stability and solubility of the drugs during the printing process. The fused filament fabrication (FFF) type 3D printing technique, owing to its precise computer-aided layer deposition, successfully provided a platform for geometric and dosage personalization, achieving high dimensional accuracy. Physicochemical characterization studies showed that CD inclusion complexes maintained drug stability during the printing process, confirmed by the absence of free crystalline drug. Furthermore, drug:CD complexes significantly enhanced the mechanical properties of PCL, thereby increasing strength and toughness, which are critical for intrauterine stability. <em>In vitro</em> release studies demonstrated a sustained, controlled release profile, exceeding 80% over 9 months for PCX and 4 months for CBP. Cytotoxicity studies showed that drug-free IUDs were non-cytotoxic and non-genotoxic to healthy L929 mouse fibroblast cells. Furthermore, <em>in vivo</em> studies demonstrated that IUDs did not cause dermal irritation. The drug-containing IUDs were found to be at least as effective as the drug solution on HEC-1B endometrial cancer cells. Lastly, <em>ex vivo</em> studies confirmed favorable bioadhesion of IUDs and high drug retention within uterine tissue. All these findings validate the FFF-type 3D printing as a promising and flexible approach for preparing personalized, biocompatible, and effective local drug delivery systems for the treatment of uterine cancer.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"219 ","pages":"Article 107456"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146099930","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":"Retraction notice to \"Vaginal suppositories of cumin seeds essential oil for treatment of vaginal candidiasis: Formulation, in vitro, in vivo, and clinical evaluation\" [European Journal of Pharmaceutical Sciences 157 (2021)105602].","authors":"Noura H Abd Ellah, Asmaa S Shaltout, Shreen M M Abd El Aziz, Ahmed M Abbas, Hasnaa G Abd El Moneem, Entisar M Youness, Amal F Arief, Marwa F Ali, Basma N Abd El-Hamid","doi":"10.1016/j.ejps.2026.107505","DOIUrl":"10.1016/j.ejps.2026.107505","url":null,"abstract":"","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":" ","pages":"107505"},"PeriodicalIF":4.7,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572966","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":"Viva la pharmacie - Spotlight on pharmaceutical manufacturing science.","authors":"Jukka Rantanen, Jarkko Ketolainen","doi":"10.1016/j.ejps.2026.107508","DOIUrl":"10.1016/j.ejps.2026.107508","url":null,"abstract":"","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":" ","pages":"107508"},"PeriodicalIF":4.7,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147510638","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":"Smart Lipid-Based Nanocarrier System for the Topical Delivery of Ocular Therapeutics Bio-Interfacing, Physicochemical Diversity, and Routing Barriers.","authors":"Manisha Singh, Snigdha Singh, Punya Sharma, Rbanshi Bhandari, Nandini Sharma, Rashi Rajput, Vivek Gupta, Sachin Kumar Singh, Kamal Dua, Nitin Chitranshi, Sujata Basu","doi":"10.1016/j.ejps.2026.107506","DOIUrl":"https://doi.org/10.1016/j.ejps.2026.107506","url":null,"abstract":"<p><p>Delivering the drug to the eye using topical delivery poses significant challenges, owing to precorneal obstacles, rapid clearance mechanisms, and adverse bioavailability. The recent development of smart lipid-based nanocarriers, including solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), liposomes, nanoemulsions, and micelles, has demonstrated the capability to address these limitations by increasing mucoadhesion, slowing release, and facilitating penetration of drugs through the epithelial lining. The review examines the categorisation, design concepts, and bio-interfacing strategies of the lipid-based delivery system used in the ocular application. This review focuses on the physicochemical diversity and the capability of traversing the ocular barriers. Several formulations exhibit promising translational applicability, including chitosan-coated SLNs of ofloxacin, which increased transcorneal permeation as compared to commercial drops, and NLCs containing diosmin, which exhibited anti-inflammatory activity and cytocompatibility in in vitro tests against retinal cells. In vivo, ripasudil in liposomes protected fibrosis in the subretinal layer, and NLCs of ciprofloxacin and natamycin enhanced antimicrobial activity with a dual drug combination. Stimuli-responsive systems, such as temperature-sensitive and pH-sensitive hydrogels, offer prolonged ocular residence time and site-specific delivery in the eye. Preclinical studies also support the potential application of SLNs of bimatoprost in the long-term reduction of intraocular pressure and PEGylated NLC in protein delivery in posterior segment diseases. The review has also discussed formulation scalability, toxicity, and regulatory barrier problems, and it also explores future integration with personalised medicine and non-invasive delivery platforms.</p>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":" ","pages":"107506"},"PeriodicalIF":4.7,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147491071","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":"Targeting the DKK1/CSF1 signaling axis to reprogram M2 macrophages and reverse chemoresistance in head and neck squamous cell carcinoma","authors":"Chin-Sheng Huang ,&nbsp;Chih-Ming Huang ,&nbsp;Hang Huong Ling ,&nbsp;Mao-Suan Huang ,&nbsp;Ming-Shou Hsieh ,&nbsp;Jia-Hong Chen","doi":"10.1016/j.ejps.2026.107435","DOIUrl":"10.1016/j.ejps.2026.107435","url":null,"abstract":"<div><h3>Background</h3><div>Understanding the mechanisms underlying drug resistance in head and neck squamous cell carcinoma (HNSCC) is critical for the development of effective therapeutic strategies. M2-type tumor-associated macrophages (M2-TAMs), activated by colony-stimulating factor 1 (CSF1), play a pivotal role in promoting chemoresistance and metastasis through immunosuppressive signaling and tumor–immune crosstalk. However, the precise mechanisms of CSF1-driven tumor support and macrophage activation remain incompletely understood.</div></div><div><h3>Methods</h3><div>We employed humanized patient-derived xenograft (PDX) models of drug-resistant HNSCC to examine the functional roles of CSF1 and its downstream effectors. Drug-tolerant persister (DTP) cells derived from these models were subjected to transcriptomic profiling. In vitro, both direct and indirect co-culture systems were used to assess the impact of CSF1 modulation on tumor cell viability and M2 macrophage activity. The therapeutic potential of the CSF1R inhibitor pexidartinib (PLX3397), alone and in combination with cisplatin, was evaluated in vivo.</div></div><div><h3>Results</h3><div>Our findings revealed that CSF1 silencing in M2 macrophages reduced the viability of cisplatin-resistant SCC9-P and HSC3-P cells in an indirect co-culture system, indicating a paracrine survival signal. In contrast, CSF1 overexpression enhanced tumor cell proliferation. In direct co-culture, CSF1 silencing inhibited M2 macrophage activation, whereas CSF1 overexpression promoted M2 proliferation and immunosuppressive activity. In vivo, pexidartinib effectively disrupted CSF1-mediated resistance and reduced the expression of key tumor-promoting factors, including DKK1, IL10, CXCL12, and AKT1. Clinically, high DKK1 and CSF1 expression correlated with cisplatin resistance and poor prognosis.</div></div><div><h3>Conclusion</h3><div>This study underscores the dual role of CSF1 in regulating both tumor survival and M2 macrophage activation in HNSCC. Targeting the DKK1/CSF1 axis may represent a promising strategy to overcome chemoresistance by disrupting tumor–macrophage crosstalk and reprogramming the immunosuppressive microenvironment.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"218 ","pages":"Article 107435"},"PeriodicalIF":4.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145965775","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":"Assembled fixed-dose combination tablet for hypertension: A modular design inspired by LEGO® architecture","authors":"Tanikan Sangnim ,&nbsp;Kittipat Suwanpitak ,&nbsp;Pornsak Sriamornsak ,&nbsp;Kampanart Huanbutta","doi":"10.1016/j.ejps.2026.107430","DOIUrl":"10.1016/j.ejps.2026.107430","url":null,"abstract":"<div><div>Polypharmacy in chronic diseases like hypertension often compromises patient adherence and therapeutic success due to complex regimens. While conventional fixed-dose combination (FDC) tablets improve adherence, they lack the dose flexibility needed for personalized treatment. This study addresses this gap by developing and characterizing a novel, LEGO®-inspired assemblable FDC tablet system for customizable antihypertensive therapy. Using 3D-printed molds, individual, stackable modules containing either Amlodipine, Valsartan, or Hydrochlorothiazide (HCTZ) were created. The study evaluated two polymer matrices, revealing a critical dependence on the active pharmaceutical ingredient (API). Gelatin-based matrices were effective for Amlodipine and Valsartan, achieving rapid drug with USP dissolution standards; however, this matrix was incompatible release (&gt;90% within 30 min) compliant with HCTZ. Conversely, an HPMC-based matrix successfully formulated HCTZ with a controlled-release profile but was unsuitable for the other two drugs. This work validates the proof-of-concept for a modular FDC system as a promising platform for personalized polypharmacy. However, it also highlights that achieving desired drug release profiles requires careful, API-specific polymer selection, presenting a key formulation challenge for this innovative approach.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"218 ","pages":"Article 107430"},"PeriodicalIF":4.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941418","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":"BM-164 (an H₂S-donor) modulates microRNA expression associated with reperfusion-induced ventricular fibrillation in rat hearts","authors":"E. Szabó ,&nbsp;J. Király ,&nbsp;A.B. Mondal ,&nbsp;I. Bereczki ,&nbsp;Z. Szabó ,&nbsp;Á. Tósaki","doi":"10.1016/j.ejps.2026.107433","DOIUrl":"10.1016/j.ejps.2026.107433","url":null,"abstract":"<div><div>Ventricular arrhythmias are a leading cause of sudden cardiac death in myocardial infarction and heart failure. Reperfusion following ischemia can trigger severe arrhythmias, including ventricular fibrillation (VF), and microRNAs (miRNAs) which are increasingly recognized as critical regulators of these processes.</div><div>This study aimed to identify miRNAs associated with ischemia/reperfusion (I/R)-induced ventricular fibrillation by comparing expression profiles between fibrillated (VF) and non-fibrillated (No VF) rat hearts. Nanostring-based screening (<em>n</em> = 12; 4 in each group: No I/R control, I/R no VF, and I/R VF) identified several ischemia-associated miRNAs, including rno-miR-30d, rno-miR-99a, rno-miR-130a, rno-miR-133a, rno-miR-181a, and rno-miR-191a. These candidates were subsequently validated in a larger cohort using TaqMan qRT-PCR (qPCR), including BM-164- and ascorbic acid (AA)-pretreated I/R groups administered 10 min before I/R (<em>n</em> = 6 per group). The selection of these miRNAs was guided by prior literature demonstrating their established roles in ischemia-related pathways and cardioprotection, providing a biologically grounded rationale for their inclusion.</div><div>qPCR analysis, compared with Nanostring data on a Rat miRNA panel v1.5 (425 miRNAs), revealed significant alterations in a subset of these miRNAs in I/R hearts, particularly in VF-affected samples. BM-164, an H_₂S-donor, and to a lesser extent AA, were associated with partial restoration or upregulation of these miRNAs. These findings suggest that the examined miRNAs, particularly miR-99a, miR-191a, miR-30d, and miR-181a, are likely involved in the development of reperfusion-induced ventricular arrhythmias. BM-164 pretreatment was associated with changes of these miRNAs, which have been previously implicated in autophagy and apoptosis pathways; further studies are warranted to determine whether these alterations directly mediate cardioprotection or anti-arrhythmic effects.</div><div>Given the limited sample size, these findings should be considered preliminary. Larger cohorts and additional in vivo studies are required to clarify whether these miRNA alterations causally contribute to arrhythmogenesis or represent protective responses.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"218 ","pages":"Article 107433"},"PeriodicalIF":4.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145942953","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":"Impact of cocrystal dissolution-supersaturation-precipitation (DSP) behaviour on drug permeation across the PermeaPad® biomimetic barrier","authors":"Lucy May Newman ,&nbsp;Matteo Guidetti ,&nbsp;Annette Bauer-Brandl ,&nbsp;Naír Rodríguez-Hornedo ,&nbsp;Tatiane Cogo Machado","doi":"10.1016/j.ejps.2025.107426","DOIUrl":"10.1016/j.ejps.2025.107426","url":null,"abstract":"<div><div>The purpose of this study was to evaluate how the dissolution-supersaturation-precipitation (DSP) behaviour of cocrystals translates into drug permeation<strong>,</strong> employing the biomimetic PermeaPad® barrier in a side-by-side cell set-up. Building on our previous work, which demonstrated that reducing an unnecessarily high cocrystal solubility advantage (SA = S_cocrystal/S_drug) through the generation of non-stoichiometric solution conditions can significantly extend the drug supersaturation, we now investigate this approach in the presence of an absorptive environment. Our findings with the 1:1 ketoconazole (KTZ) -<em>p</em>-aminobenzoic acid (PABA) cocrystal indicate the existence of an optimal SA value (7), where KTZ-PABA dissolution performance resulted in 8-fold AUC increase, translating to a 7-fold increase in cumulative KTZ permeation after 6 h. This enhancement was achieved by dissolving cocrystal (based on the drug therapeutic dose) with an additional coformer solid phase, rationally designed using a graphical approach grounded in the cocrystal thermodynamic (K_sp, S_cocrystal, S_drug) and kinetic parameters (σ_crit). The strategy presented in this work can be readily applied during the pre-formulation stage of cocrystal development, enabling targeted selection of coformer concentrations for formulation development. Overall cocrystals offer unique flexibility as a formulation strategy for poorly water-soluble drugs, allowing for tailored DSP behaviour and drug transport over biological barriers based on mechanistic understanding<strong>,</strong> as demonstrated in this study.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"218 ","pages":"Article 107426"},"PeriodicalIF":4.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145896350","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}