International Journal of Pharmaceutics: X最新文献

{"title":"Synergistic photodynamic and chemodynamic therapy using hypoxia-adaptive Ce6@Co nanoparticles for enhanced tumor suppression","authors":"Yeji Chang,&nbsp;Yong Geun Lim,&nbsp;Kyeongsoon Park","doi":"10.1016/j.ijpx.2025.100348","DOIUrl":"10.1016/j.ijpx.2025.100348","url":null,"abstract":"<div><div>Conventional photodynamic therapy (PDT) is less effective in solid tumors owing to Type-II PDT mechanism's reliance on oxygen (O₂), which is scarce in hypoxic environments. Most hydrophobic photosensitizers have poor water solubility, complicating their formulation and delivery. To address these challenges, Ce6@Co nanoparticles (a hypoxia-adaptive nanoplatform) were developed via coordinating Co²⁺ ions with chlorin e6 (Ce6), exhibiting uniform size (∼230 nm), enhanced dispersibility, and colloidal stability. These nanoparticles generate dual-mode reactive oxygen species (ROS): Type-II ¹O₂ via PDT under 670 nm irradiation and oxygen-independent hydroxyl radical (⋅OH) via Co²⁺-mediated Fenton-like reactions. In vitro, Ce6@Co nanoparticles demonstrated superior cellular uptake and robust ROS amplification, and reduced squamous cell carcinoma (SCC7) cell viability to 34.4 % under normoxia and 20.48 % under hypoxia via synergistic photodynamic and chemodynamic (PDT-CDT) effects, causing considerable apoptosis. In vivo, intratumoral administration of Ce6@Co nanoparticles via laser irradiation completely suppressed tumors in SCC7 tumor-bearing mice. This effect was attributed to favorable intratumoral distribution, enhanced retention, and synergistic PDT-CDT. No systemic toxicity was observed, as indicated by stable body weight, normal serum biomarkers, and unchanged organ histology. The Co²⁺-coordinated photosensitizer system uses hypoxia-elevated H₂O₂ to sustain CDT, effectively overcoming conventional PDT's oxygen dependence and offering a safe and effective dual-modal therapeutic strategy for hypoxic solid tumors.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100348"},"PeriodicalIF":5.2,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338856","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}

{"title":"Development of an inhalable dry powder formulation for inhibition of SARS-CoV-2","authors":"Justin Stella ,&nbsp;Anja Germann ,&nbsp;Oliver Janka ,&nbsp;Sylvia Wagner ,&nbsp;Marc Schneider","doi":"10.1016/j.ijpx.2025.100346","DOIUrl":"10.1016/j.ijpx.2025.100346","url":null,"abstract":"<div><div>Coronaviruses, including SARS-CoV-2, can cause significant lung damage and may result in multiple organ failure. The severity of COVID-19 is determined by the virus's entry into lung tissue and subsequent replication. This entry is facilitated by the angiotensin-converting enzyme 2 (ACE2) in combination with the serine protease TMPRSS2, which is a critical step. To reduce viral replication, it is necessary to prevent the uptake of the virus directly at the main route of transmission, which is the deposition of the virus as an aerosol in the respiratory tract. To reduce viral uptake into lung cells, an inhalable dry powder formulation was developed. The formulation contains camostat, a clinically proven serine protease inhibitor that inhibits the cellular uptake mechanisms on the lung surface. Camostat was spray-dried together with the mucolytic agent <em>N</em>-acetylcysteine to produce co-amorphous microparticles with sufficient solubility after deposition. Microparticles with properties suited for deposition in the deep part of the respiratory tract can be produced by using appropriate spray-drying parameters. The use of L-leucine enabled suitable aerodynamic properties and storage stability due to reduced interaction with environmental water. The geometric particle diameter, determined using laser light diffraction, decreased with L-leucine content which was found forming a partially crystalline L-leucine shell. The disintegration behavior of the microparticle formulation simulated under lung-like conditions indicated fast disintegration. A pseudo-viral <em>in vitro</em> assay demonstrated low acute toxicity in combination with a high activity. Cell viability and proliferation were not affected by camostat concentrations up to 11.1 μg/mL. The IC₅₀ values of the two dry powder formulations tested on a HEK293T/ACE2-TMPRSS2 cell line were 0.008 μg/mL and 0.019 μg/mL, respectively, which is at least 100 times lower than the cytotoxic concentration. This dry powder formulation serves as a prototype microparticle matrix for incorporating nanoscale drug carriers in the future.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100346"},"PeriodicalIF":5.2,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314002","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}

{"title":"Oral delivery of Kaempferia parviflora's methoxyflavones via nanostructured lipid carriers: Its effect on obesity and dyslipidemia treatment”","authors":"Natchanon Rimsueb ,&nbsp;Peera Tabboon ,&nbsp;Phichaporn Bunwatcharaphansakun ,&nbsp;Uracha Ruktanonchai ,&nbsp;Katawut Namdee ,&nbsp;Udom Asawapirom ,&nbsp;Bungorn Sripanidkulchai ,&nbsp;Sarunya Tuntiyasawasdikul ,&nbsp;Somsuda Somintara ,&nbsp;Tawut Rudtanatip ,&nbsp;Mattaka Khongkow","doi":"10.1016/j.ijpx.2025.100345","DOIUrl":"10.1016/j.ijpx.2025.100345","url":null,"abstract":"<div><div><em>Kaempferia parviflora</em> extract (BG), commonly known as Black Ginger, is a plant native to Thailand and other Southeast Asian countries. Its methoxyflavones are active compounds widely used in dietary supplements. However, their oral administration faces challenges due to poor stability, low gastrointestinal bioavailability, and limited absorption. This study developed a nanostructured lipid carrier (NLC) encapsulating BG to enhance GI stability, bioavailability, and efficacy <em>via</em> oral administration. The BG-NLC exhibited a homogeneously spherical morphology with an average size of 99.15 ± 0.09 nm, a zeta potential of −25.37 ± 0.99 mV, and a PDI of 0.19 ± 0.01. The particles demonstrated high stability during storage at 4 °C, 25 °C, and 40 °C for three months, following Asian health supplement stability guidelines. Furthermore, BG-NLC showed excellent physicochemical stability in simulated gastric (SGF) and intestinal fluids (SIF), significantly enhancing intestinal absorption and permeability by approximately 10–30 % compared to BG. <em>In vitro</em> studies revealed that BG-NLC significantly reduced lipid accumulation and triglyceride production in differentiated adipocytes, surpassing the performance of BG. <em>In vivo</em> studies in a high fat-diet induced obesity mouse model further demonstrated improved BG bioavailability, resulting in reductions in body weight, body mass index (BMI), and liver and adipose tissue weights. In summary, BG-NLC exhibits high stability in simulated GI conditions, improved intestinal absorption, and notable anti-adipogenic effects, alongside potential benefits for blood sugar regulation. These findings highlight the potential of BG-NLC as a novel and effective formulation for health supplements and pharmaceutical products targeting metabolic-related diseases.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100345"},"PeriodicalIF":5.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144271992","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}

{"title":"The effect of black tea and water temperature on the disintegration of gelatine and HPMC capsules, tested with the paddle device, GastroDuo and in vivo pharmacokinetics: Much ado about little","authors":"Dorota Sarwinska ,&nbsp;Mathilde Leyh ,&nbsp;Constantin Foja ,&nbsp;Theodora Tzakri ,&nbsp;Philipp Schick ,&nbsp;Felix Morof ,&nbsp;Julius Krause ,&nbsp;James Mann ,&nbsp;Richard Barker ,&nbsp;Mladen Vassilev Tzvetkov ,&nbsp;Werner Weitschies ,&nbsp;Michael Grimm","doi":"10.1016/j.ijpx.2025.100342","DOIUrl":"10.1016/j.ijpx.2025.100342","url":null,"abstract":"<div><div>Fluid co-administered with oral medication directly affects its behaviour. Often, people use fluids other than water when taking their medications. Capsules (mainly gelatine- and HPMC-based) are widely used solid oral dosage forms. The presented study aimed to investigate the behaviour of gelatine and HPMC capsules in several fluids <em>in vitro</em> and <em>in vivo</em>. The second aim was to assess the influence of administered fluids on the gastric emptying. The third aim was to assess the usability and predictive power of different <em>in vitro</em> methods for drug analysis and compare them with <em>in vivo</em> data. For <em>in vitro</em> studies, two systems with different complexities were used: the compendial USP 2 apparatus and the GastroDuo biorelevant model. In both systems, 25 mL of SGF and 240 mL of tested fluid were used. To obtain the <em>in vivo</em> data, a clinical study with 12 young and healthy volunteers was performed. In this study, the salivary tracer technique, which utilises caffeine kinetics as a marker of a dosage form behaviour in the GIT, was used. <em>In vitro</em>, the temperature strongly affected the opening times of gelatine capsules (rapid opening in warm media and slower in cold). <em>In vivo</em>, the opening time of gelatine capsules in warm black tea was slightly delayed in comparison to warm water. The differences in opening times between warm and cold water and warm black tea and cold water were significant. In USP 2 Apparatus, HPMC capsules were more sensitive to the tested media than in the biorelevant GastroDuo model. There were no significant differences in the opening times of HPMC capsules <em>in vivo</em>. Gastric emptying of warm water, cold water or warm black tea was not affected, suggesting that the altered <em>in vivo</em> absorption kinetics was caused by the <em>in vivo</em> behaviour of the capsules, depending on their properties and not by changes in the gastric emptying of the co-administered fluids. The presented study allows a better understanding of gelatine and HPMC capsules behaviour <em>in vitro</em> and <em>in vivo</em> administered with different fluids. Moreover, it demonstrated the relevance of <em>in vivo</em> data as well as the limitations of <em>in vitro</em> tools.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100342"},"PeriodicalIF":5.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144178312","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}

{"title":"Neutrophil-Mimetic oleanolic acid-loaded Liposomes targeted to alleviate oxidative stress for renal ischemia-reperfusion injury treatment","authors":"Qiaojing Chen ,&nbsp;Daping Xiao ,&nbsp;Yi Wang ,&nbsp;Zheng Zhang ,&nbsp;Xinlu Lin ,&nbsp;Qing Ji ,&nbsp;Yingmin Han ,&nbsp;Lingan Yu ,&nbsp;Jinglin Xu","doi":"10.1016/j.ijpx.2025.100344","DOIUrl":"10.1016/j.ijpx.2025.100344","url":null,"abstract":"<div><div>Acute kidney injury (AKI) is a prevalent clinical condition characterized by a sudden decline or loss of renal function, exacerbated by the lack of effective diagnostic and therapeutic tools. Renal ischemia-reperfusion injury serves as the primary cause of AKI, initiating a complex signaling cascade that mediates renal cell necrosis, apoptosis, and inflammation. Oxidative stress plays a crucial role in the pathogenesis and progression of ischemia-reperfusion injury, thus prompting the exploration of antioxidants as potential therapeutic interventions. Oleanolic acid, derived from natural plant extracts, exhibits significant antioxidant and anti-inflammatory properties; however, its clinical application has been hindered by inherent limitations such as poor water solubility and low bioavailability. To address this issue, we developed an innovative approach involving oleanolic acid-loaded liposomes fused with neutrophil membranes, resulting in hybrid liposomes (N-OAL). This strategy aims to enhance the accumulation and retention of N-OAL at inflammatory sites associated with AKI through biomimetic chemotaxis mediated by neutrophil membranes specifically targeting damaged renal tubular epithelial cells. The optimized N-OAL presented a spherical morphology with an average particle size of 125.6 ± 4.9 nm and a surface potential of −4.8 ± 0.3 mV. In addition, N-OAL exhibited favorable sustained release, outstanding stability, and satisfactory biocompatibility. <em>In vitro</em> studies demonstrated that N-OAL effectively attenuated H₂O₂-induced intracellular reactive oxygen species generation and inflammation while exhibiting superior antioxidant and anti-apoptotic properties. Furthermore, our <em>in vivo</em> results confirmed the remarkable protective effect of N-OAL on oxidative-damaged renal tissue caused by AKI induction. Overall, our study provides novel insights into targeted delivery strategies for oleanolic acid therapy in acute kidney injury.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100344"},"PeriodicalIF":5.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144221510","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}

{"title":"Development, characterization, and in vitro evaluation of poly(ethylene oxide)-block-poly(ε-caprolactone)-α-tocopheryl succinate micelles as a novel nanocarrier for rapamycin delivery","authors":"Ziyad Binkhathlan ,&nbsp;Abdullah K. Alshememry ,&nbsp;Ahmad M. Balkhair ,&nbsp;Raisuddin Ali ,&nbsp;Sulaiman S. Alhudaithi ,&nbsp;Saad Alobid ,&nbsp;Wajhul Qamar ,&nbsp;Alhassan H. Aodah ,&nbsp;Mohammad Reza Vakili ,&nbsp;Afsaneh Lavasanifar","doi":"10.1016/j.ijpx.2025.100341","DOIUrl":"10.1016/j.ijpx.2025.100341","url":null,"abstract":"<div><div>Rapamycin holds significant therapeutic potential for various diseases; however, its clinical application is limited by several formulation challenges, primarily its extremely low aqueous solubility (2.6 μg/mL). To address this, nanoparticle-based delivery systems have emerged as a promising strategy to enhance solubility and enable sustained drug release. Currently, Fyarro® (Aadi Bioscience, Inc.), an albumin-bound nanoparticle formulation, is the only FDA-approved injectable rapamycin product. In this study, we aimed to develop and evaluate novel poly(ethylene oxide)-<em>block</em>-poly(ε-caprolactone)-α-tocopheryl succinate (PEO-<em>b</em>-PCL-α-TS) micelles and assess their potential as a delivery system for rapamycin. PEO-<em>b</em>-PCL copolymers with varying PCL/PEO ratios were prepared <em>via</em> ring-opening polymerization and modified by α-TS conjugation, as confirmed by ¹H NMR, GPC, XRD, DSC analyses. The optimum rapamycin-loaded micelles (PEO₂₀₀₀-<em>b</em>-PCL₄₀₀₀-α-TS) exhibited nano-sized particles (&lt; 22 nm) with a narrow polydispersity index (&lt;0.29), high drug encapsulation efficiency (≥92 %), and enhanced solubility (&gt;1.3 mg/mL). Stability studies demonstrated that encapsulation protected rapamycin from degradation, maintaining over 90 % drug retention for three months at 4 °C, while <em>in vitro</em> release studies showed sustained release, with 50 % of rapamycin released from PEO₂₀₀₀-<em>b</em>-PCL₄₀₀₀-α-TS micelles over 72 h. <em>In vitro</em> cytotoxicity assays revealed anticancer activity against lung carcinoma epithelial cells (A549), and the human colon adenocarcinoma cell line (HCT116). Minimal toxicity (≥70 % viability) was observed in normal human fibroblast cells (HFF1). These results point to the potential of PEO-<em>b</em>-PCL-α-TS micelles as a promising nanocarrier system, offering improved rapamycin solubility, enhanced stability, sustained release, and effective anticancer activity.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100341"},"PeriodicalIF":5.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144178302","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}

{"title":"Corrigendum to “Impact of polymer chemistry on critical quality attributes of selective laser sintering 3D printed solid oral dosage forms” [International Journal of Pharmaceutics:X Volume 6 (2023) 100203]","authors":"Evgenii Tikhomirov ,&nbsp;Valerie Levine ,&nbsp;Michelle Åhlén ,&nbsp;Nicole Di Gallo ,&nbsp;Maria Strømme ,&nbsp;Thomas Kipping ,&nbsp;Julian Quodbach ,&nbsp;Jonas Lindh","doi":"10.1016/j.ijpx.2025.100319","DOIUrl":"10.1016/j.ijpx.2025.100319","url":null,"abstract":"","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100319"},"PeriodicalIF":5.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144298968","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}

{"title":"Co-assembled Glycyrrhiza nanoparticles embedded supramolecular protein hydrogels to enhance licochalcone A release for acute inflammation management","authors":"Zhuxian Wang ,&nbsp;Jun Liu ,&nbsp;Yufan Wu ,&nbsp;Yamei Li ,&nbsp;Hongxia Zhu ,&nbsp;Qiang Liu ,&nbsp;Bin Yang","doi":"10.1016/j.ijpx.2025.100343","DOIUrl":"10.1016/j.ijpx.2025.100343","url":null,"abstract":"<div><div>Licochalcone A (LA) garnered remarkable acclaim in acute inflammation therapy, however, poor release capability from the matrix and oral bioavailability restrict its oral delivery. To address this challenge, licorice-derived glycyrrhizic acid (GA) and LA were co-assembled into GA-LA (GLA) binary co-assembled <em>Glycyrrhiza</em> nanoparticles (BCGNs), which were subsequently incorporated into supramolecular hydrogel matrix. GLA BCGNs demonstrated a remarkable capacity to scavenge various reactive oxygen species (ROS) and facilitated the cascade process of O₂^•−-H₂O₂-O₂ in vitro. Subsequently, GLA was dispersed in nano form into ovalbumin (OVA) and rhamnose (Rha) solutions, which were next self-assembled into OVA-Rha-GLA hydrogels. Remarkably, the introduction of Rha induced disordered secondary conformation of OVA, which decreased its mechanical properties and inherent binding energy, thereby shaping the three-dimensional supramolecular spatial structures of OVA-Rha-GLA networks. The assembly mechanisms indicated that the hydrogen bonding predominantly drove the assembly of loose supramolecular networks surrounded by -OH, -CH₂ and C<img>O bonds on the Rha and OVA. Notably, the conformational transformation facilitated faster LA release, confirmed by computational simulation analysis, which was conducive to acute inflammation curation. Therefore, OVA-Rha-GLA exhibited excellent anti-inflammation and ROS-scavenging versatilities, displaying improved oral bioavailability compared to hydrogels lacking BCGNs or Rha in cellular and animal acute inflammation experiments. The results provided novel BCGNs-embedded supramolecular hydrogel systems to improve the drug release and anti-inflammatory bioactivities of LA, which demonstrated great promise in the management of acute inflammation.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100343"},"PeriodicalIF":5.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144189951","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}

{"title":"Glycyrrhizic acid and its carrier-free micellar formulation: Unraveling the potential for enhanced oral prevention of hearing loss","authors":"Huaan Li ,&nbsp;Bohan Lin ,&nbsp;Shuangwu Wang ,&nbsp;Ying Zhang ,&nbsp;Zeming Zhou ,&nbsp;Dingsheng Wen ,&nbsp;Zhifeng Zhang ,&nbsp;Xiaohua Feng ,&nbsp;Lu Wen ,&nbsp;Jun He ,&nbsp;Gang Chen","doi":"10.1016/j.ijpx.2025.100340","DOIUrl":"10.1016/j.ijpx.2025.100340","url":null,"abstract":"<div><div>Hearing loss, a global health concern, significantly impacts patients with delayed language development, impaired neurocognitive function, and severe social problems. The main cause is the cochlear hair cell damage induced by oxidative stress and inflammation from ototoxic drugs, noise exposure or diabetes. Glycyrrhizic acid (GA), derived from edible herb licorice, is widely utilized in traditional Chinese medicine and clinical treatments for liver diseases. However, its potential in preventing hearing loss remains largely unexplored. Herein, we propose GA as a novel otoprotective agent and demonstrate its capability to prevent hearing loss. Our results show that GA effectively reduces oxidative stress and inflammation induced by cisplatin, aminoglycosides, or even noise and diabetes, thereby protecting cochlear hair cells. In hearing loss models, two commonly used administration methods were compared, with tympanic injection providing better protective effects than oral administration of GA. To enhance oral bioavailability, GA is employed as both the medicine and excipient, and formulated into micelles with curcumin, another extensively used bioactive compound. Interestingly, formulation parameters such as feeding ratio and temperature have little impact on micelle size but significantly affect the drug loading efficiency. The carrier-free strategy can achieve a high drug loading capacity and significantly increase the drug concentration in blood, offering improved preventive efficacy. Notably, the micelles also exhibit protection on kidneys and liver, and do not compromise the antitumor activity of cisplatin. Therefore, GA holds promise as an otoprotective candidate, with potential clinical applications for oral prophylaxis of hearing loss using the micellar formulation.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100340"},"PeriodicalIF":5.2,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144170464","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}

{"title":"A pragmatic mixing model for the evaluation of powder flow properties of multicomponent pharmaceutical blends","authors":"Daniel Yanes ,&nbsp;Rachael Shinebaum ,&nbsp;Georgios Papakostas ,&nbsp;Gavin K. Reynolds ,&nbsp;Sadie M.E. Swainson","doi":"10.1016/j.ijpx.2025.100339","DOIUrl":"10.1016/j.ijpx.2025.100339","url":null,"abstract":"<div><div>Maintaining flowability of pharmaceutical blends is critical for operational efficiency in state-of-the-art continuous direct compression (CDC) manufacturing, with poor flow potentially resulting in API loss, increased experimental work and increased time to market. Consequently, flowability is a crucial consideration in the design of formulations and must be considered throughout the development process when changes are introduced. Traditionally, understanding flow properties has required testing large amounts of material, particularly when evaluating formulation options. This has led to research into developing predictive flow models to reduce experimental burden. Current models with good predictive capacity, such as using granular bond number, require non-routine measurements such as mechanical surface energy. Three mixture designs, each using three pharmaceutical materials, were developed to investigate flow properties and allow the evaluation of a number of mixing models for predicting flowability with minimal experimental input requirements. The resultant models ranged in complexity from simple first order mixture models to more complex third order models with binary and ternary interaction parameters. An analysis of the experimental cost versus prediction accuracy suggested that while the more complex models delivered the most accurate predictions, a first order mass weighted model using inverse FFC was capable of providing good predictions in return for a more manageable experimental burden, with an R² value of 0.68, root mean square error of 2.88 and a mean absolute percentage error of 0.21. This model has the potential to provide valuable insights during early formulation design and development where material is scarce and good flowability is crucial.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"9 ","pages":"Article 100339"},"PeriodicalIF":5.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144124987","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}