International Journal of Pharmaceutics最新文献

{"title":"Evaluation, correction and masking methods for unpleasant tastes of drugs: A comprehensive review.","authors":"Fan Zhang, Longfei Lin, Zhixin Wang, Hui Li","doi":"10.1016/j.ijpharm.2025.126008","DOIUrl":"10.1016/j.ijpharm.2025.126008","url":null,"abstract":"<p><p>The unpleasant tastes of drugs, including bitterness, pungency, astringency, and sourness, significantly impedes patient adherence, particularly among pediatric and geriatric populations. Accurate evaluation of these tastes is essential for optimizing formulations and improving drug quality during development. Developing effective taste correction and masking strategies has become a pivotal challenge in pharmaceutics, aiming to improve palatability by concealing unpleasant tastes or modulating sensory perception without compromising therapeutic efficacy. To address these challenges, a comprehensive understanding of current methodologies and innovative strategies is crucial for advancing patient-centric drug design. This review systematically summarizes evaluation methods, correction strategies, and masking techniques for drug-related unpleasant tastes, providing theoretical and technical insights for optimizing drug palatability. Initially, the physiological mechanisms underlying the four types of unpleasant drug tastes are described. Quantitative evaluation techniques, including sensory panels, chemical assays, biological assessments, electronic tongues and biosensors are systematically examined, with a particular emphasis on biosensors due to their remarkable sensitivity and biomimetic properties. Additionally, strategies to ameliorate palatability are elaborated. Taste correction involves the use of sweeteners, sour agents, and flavor enhancers, while taste masking employs physical barriers, chemical modifications, or biomaterial-based encapsulation to minimize drug-taste bud interactions. Subsequently, prospective avenues are suggested, highlighting the potential of interdisciplinary innovations such as artificial intelligence (AI)-driven predictive models and nanotechnology-based delivery systems. These advancements hold the promise of revolutionizing the precision and efficacy of taste evaluation and masking, ultimately propelling personalized drug development forward.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126008"},"PeriodicalIF":5.2,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764822","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":"Optimization of bipolar iontophoresis parameters for the skin penetration of a negatively charged hydrophilic cosmetic active.","authors":"Tiffanie Salas, Claire Bordes, Baptiste Bonnemaire, Lucie Clarey, Cynthia Barratier, Marie-Alexandrine Bolzinger","doi":"10.1016/j.ijpharm.2025.126013","DOIUrl":"10.1016/j.ijpharm.2025.126013","url":null,"abstract":"<p><p>Iontophoresis uses low electrical currents to enhance the transdermal delivery of ionic drugs through a combined effect of electromigration (EM) and electroosmosis (EO). This study investigated the cutaneous penetration of an anti-ageing agent, ascorbyl glucoside (AA2G), loaded in a simple buffered aqueous gel, using cathodal direct current iontophoresis. The iontophoresis device consisted of two electrodes applied side by side to the skin surface. For gels prepared at pH 2.6, AA2G was only slightly ionized, and despite the positive skin surface charge, the application of an electric current of 0.1 mA/cm² had no impact on AA2G skin penetration compared to passive diffusion. However, at pH 6, where AA2G is highly ionized and the skin explant is negatively charged, the similar contributions of electroosmosis and electromigration led to a significantly higher total amount of AA2G in the skin (Qtot ∼1.697 ± 0.178 µg/cm²) than with passive diffusion (Qtot ∼0.258 ± 0.105 µg/cm²). This corresponded to a 9.6-fold improvement in AA2G penetration into its target skin layers (dermis and epidermis). At higher current densities (above 0.2 mA/cm²), EM of AA2G increased further, but skin polarization and the increased transport of mobile cations (endogenous and from the buffered gel) resulted in greater electroosmotic flux, thus reducing AA2G overall cutaneous penetration. The results also showed that depositing the AA2G formulation under both electrodes, with no formulation in between, promoted AA2G skin penetration, whatever the current intensity. Cathodic iontophoresis is suitable for the transdermal delivery of AA2G, a small, hydrophilic and negatively charged molecule, despite the skin permselectivity to cations.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126013"},"PeriodicalIF":5.2,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764871","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":"Thermosensitive self-assemblies: A review on structural and application aspects centred at drug delivery.","authors":"Kamal Kant Kaushik, Sanjay Tiwari","doi":"10.1016/j.ijpharm.2025.126045","DOIUrl":"10.1016/j.ijpharm.2025.126045","url":null,"abstract":"<p><p>Self-assembled systems are formed by spontaneous arrangement of molecular units into nano-scaled structures with diverse morphologies. Spontaneity of formation makes these structures attractive in drug delivery and other biomedical applications. Thermosensitive self-assemblies consist of materials capable of exhibiting changes in their properties in response to changes in the temperature of microenvironment. Essentially, it happens owing to alteration in hydrogen bonding, electrostatic interactions, and molecular motions in the local region. In this review, we have discussed phase transition in polymers, peptides and lipid-based systems. The literature suggests that transition temperature of these components can be modulated through changes in block arrangement, block length and branching, the nature of hydrophobic/hydrophilic segments, concentration and incorporation of organic additives. Finally, we have reviewed the application of thermosensitive assemblies in drug delivery.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126045"},"PeriodicalIF":5.2,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784285","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":"Impact of spin-freezing parameters and excipient composition on product stability of a PEGylated peptide formulation.","authors":"Zarah Schaal, Pieter-Jan Van Bockstal, Joris Lammens, Julian H Lenger, Adrian P Funke, Stefan C Schneid, Thomas De Beer","doi":"10.1016/j.ijpharm.2025.126007","DOIUrl":"10.1016/j.ijpharm.2025.126007","url":null,"abstract":"<p><p>This study examines the impact of spin‑freezing parameters, as applied in continuous spin-freeze-drying processes, and formulation composition on the stability of a PEGylated peptide following freeze‑drying and storage. A trehalose‑based reference formulation was compared with two reformulated systems in which trehalose was replaced by either mannitol or a 75:25 sucrose-mannitol blend. Samples were processed under four distinct spin‑freezing conditions, varying in cooling and crystallization rates, followed by batch‑drying and storage at either 2-8 °C or 50 °C for up to 13 weeks. Product quality was evaluated by assessing peptide concentration, monomer content, and cake morphology. Across all formulations and storage conditions, variations in spin‑freezing parameters exhibited no consistent or statistically significant effect on peptide or monomer levels. In contrast, formulation composition emerged as the dominant stability determinant. Trehalose‑based samples maintained robust stability under both refrigerated storage and stress conditions, whereas mannitol‑based samples exhibited moderate degradation at elevated temperatures. The sucrose-mannitol formulation demonstrated pronounced instability at 50 °C, characterized by cake collapse, browning, and interference in peptide quantification, likely as a result of sucrose hydrolysis and the formation of aromatic degradation products. These findings highlight that, for the formulations investigated, the choice of excipient is critical for product stability and that systems susceptible to sugar degradation may require adapted analytical approaches, as well as optimized drying protocols and storage conditions.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126007"},"PeriodicalIF":5.2,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784282","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":"Eco-friendly development of sterile chitosan-based aerogels for wound dressing applications using integrated scCO₂ processing.","authors":"Cristiana S A Bento, José P Ruivo, Susana Alarico, Nuno Empadinhas, Emanuel Candeias, Sandra Cardoso, Hermínio C de Sousa, Ana M A Dias, Mara E M Braga","doi":"10.1016/j.ijpharm.2025.126021","DOIUrl":"10.1016/j.ijpharm.2025.126021","url":null,"abstract":"<p><p>The development of novel and eco-friendly wound dressings using biopolymers faces challenges related to their processing/sterilisation. Supercritical CO₂ (scCO₂) drying represents an efficient and sustainable solution, by enabling the production of sterilised materials with high surface area/porosity while preserving essential properties. This study introduces a novel integrated process for developing sterile chitosan (CS) aerogels crosslinked with tripolyphosphate (TPP) and polyvinyl alcohol (PVA). The process combines high-pressure solvent exchange, scCO₂ drying and sterilisation, with one additional step for active pharmaceutical ingredients (API) impregnation. Results show that the properties of the CS-based aerogels, such as surface area, porosity, swelling capacity, mechanical resistance to compression, and cytotoxicity can be tuned depending on TPP crosslinking degree. Adding PVA improves structural homogeneity and flexibility but reduces surface area and increases toxicity. The CS-TPP_2.5% aerogel emerged as the most promising, offering good mechanical properties (4.93 ± 0.75 N), high surface area (190.80 ± 9.80 m².g^-1), porosity (71.12 ± 1.41 %), and low cytotoxicity, making it suitable for wound dressings. The integrated process was successfully applied to a selected CS-based aerogel, producing a sterile aerogel loaded with naringin (model API) in a short timeframe. Overall, this work offers a green approach to produce sterile API loaded aerogels, suitable for biomedical applications.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126021"},"PeriodicalIF":5.2,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144789079","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":"One‑Step fabrication method of insulin‑loaded polycaprolactone nanofibres by blend electrospinning for diabetic wound care.","authors":"Shangjie Lian, Min Zhao, Dimitrios A Lamprou","doi":"10.1016/j.ijpharm.2025.126032","DOIUrl":"10.1016/j.ijpharm.2025.126032","url":null,"abstract":"<p><p>Effective management of diabetic wounds is a significant clinical challenge. Topical insulin shows therapeutic promise, but its delivery and stability require the use of advanced systems. This study aimed to develop and comprehensively characterise insulin-loaded Poly(ε-caprolactone) (PCL) nanofibres fabricated via a one-step blend electrospinning technique, as a potential platform for sustained insulin delivery in diabetic wound care. PCL nanofibres containing varying insulin concentrations were prepared using hexafluoroisopropanol (HFIP). The nanofibres were extensively characterised for their morphology, physicochemical properties (including thermal and chemical integrity), mechanical strength, surface wettability, insulin encapsulation efficiency (EE), and in vitro release kinetics. The stability of free insulin in solution was also assessed for comparison. Insulin incorporation significantly reduced nanofibre diameter (to ∼ 250 nm) and markedly enhanced tensile strength and Young's modulus without compromising elasticity, yielding mechanical properties within reported physiological ranges. An EE of approximately 78 % was achieved. In vitro studies demonstrated sustained insulin release over 14 days. Crucially, comparative analyses of release samples, contextualised by free insulin degradation studies, revealed that PCL nanofibre encapsulation conferred significant protection against insulin degradation compared to insulin in solution. The developed insulin-loaded PCL nanofibres, combining favourable physicochemical and mechanical properties with sustained release and enhanced protein stability, represent a promising approach for advanced diabetic wound dressings, potentially reducing dressing change frequency and improving therapeutic outcomes.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126032"},"PeriodicalIF":5.2,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804037","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":"Accelerated predictive stability (APS) strategies applied to screening pharmaceutical formulations: A comparison of spray dried and hot melt extruded nifedipine amorphous solid dispersions.","authors":"Peter O'Connell, Joshua H Yoon, Luke M Geever, Dinesh Kumar, Anne-Marie Healy, Dolores R Serrano","doi":"10.1016/j.ijpharm.2025.126012","DOIUrl":"10.1016/j.ijpharm.2025.126012","url":null,"abstract":"<p><p>This study addresses the challenges in designing stable amorphous solid dispersions (ASDs) for pharmaceutical applications, focusing on nifedipine ASDs. The research involved manufacturing four different nifedipine ASDs using scalable pharmaceutical techniques-hot melt extrusion (HME) and spray drying (SD). Two pharmaceutical grade polymers, Soluplus® and poly-vinylpyrrolidone vinyl acetate (PVPVA, Kollidon® VA64), were used as carriers. The study employed an Accelerated Predictive Stability (APS) approach to assess the stability of these formulations. This included High-Performance Liquid Chromatography (HPLC) for quantifying nifedipine degradation, Powder X-Ray Diffraction (PXRD), and Differential Scanning Calorimetry (DSC) for measuring crystallisation kinetics. Additionally, Near-Infrared (NIR) spectroscopy was utilised to develop Partial Least Squares (PLS) regression models, providing a cost-effective and non-destructive method to quantify physicochemical changes. The results revealed that all four ASDs significantly improved the dissolution rate of nifedipine compared to its crystalline form. However, notable differences in stability among the formulations were observed through APS. The SD powders demonstrated greater physical stability, evidenced by a single glass transition temperature, in contrast to the extrudates, which showed dual glass transition temperatures indicating phase separation. Conversely, the HME formulations exhibited superior chemical stability compared to their SD counterparts, with the latter showing increased moisture sensitivity. Additionally, the degradation kinetics of the SD formulations were more complex than those of the extruded materials. Under less extreme conditions, SD systems followed Avrami-type kinetics, whereas more extreme conditions led to a shift from Avrami to diffusion kinetics, likely due to the miscibility of degradation products with polymer chains. In conclusion, the SD-PVPVA64 ASD was identified as the most balanced formulation in terms of physical and chemical stability, making it a prime candidate for further development. The study underscores the effectiveness of the APS approach, combined with chemometrics, as a robust methodology for guiding decision-making in the development of pharmaceutical amorphous formulations.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126012"},"PeriodicalIF":5.2,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759972","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":"Decoding excipients in lipid-based self-emulsifying drug delivery systems: Insights into physicochemical properties and therapeutic outcomes.","authors":"Azael Francisco Silva-Neto, Alane Rafaela de Carvalho Amaral, Lucas José de Alencar Danda, Luíse Lopes Chaves, Lariza Darlene Santos Alves, Monica Felts de La Roca Soares, José Lamartine Soares-Sobrinho","doi":"10.1016/j.ijpharm.2025.126018","DOIUrl":"10.1016/j.ijpharm.2025.126018","url":null,"abstract":"<p><p>Enhancing the oral delivery of poorly water-soluble drugs remains a key challenge in pharmaceutical development. Lipid-based self-emulsifying drug delivery systems (SEDDS) offer a promising approach by improving drug solubilization, absorption, and bioavailability. Central to their performance is the physicochemical profile of excipients - such as lipids, surfactants, and cosurfactants - which govern critical aspects of formulation behavior. Parameters like hydrophilic-lipophilic balance (HLB), polarity, viscosity, and interfacial tension directly influence drug loading, self-emulsification capacity, droplet size, and colloidal stability. These properties also dictate intermolecular interactions at the oil-water interface, impacting thermodynamic stability and emulsification kinetics. Understanding these physicochemical interactions is indispensable for rational system design and successful translation to clinical outcomes. This review integrates and analyzes recent findings on how specific excipient characteristics modulate the structure, dynamics, and performance of SEDDS. Advances such as supersaturable SEDDS and mucoadhesive systems, along with solidification technologies (e.g., spray drying, adsorption, 3D printing), expand the applicability and stability of these formulations. By consolidating knowledge on excipient-function relationships, this review provides a strategic framework for the selection and combination of excipients tailored to drug properties and therapeutic goals. A deep understanding of these physicochemical parameters and their synergistic interactions is crucial for optimizing self-emulsifying formulations that are stable, efficient, and clinically effective.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126018"},"PeriodicalIF":5.2,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764820","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":"Redefining cancer treatment: the role of imatinib nanoparticles in precision medicine.","authors":"Mohd Saeed, Garima Gupta, Mohammed A S Abourehab, Prashant Kesharwani","doi":"10.1016/j.ijpharm.2025.126027","DOIUrl":"10.1016/j.ijpharm.2025.126027","url":null,"abstract":"<p><p>The world faces cancer as one of its primary mortality factors hence scientists must continuously research for enhanced treatment methods. The treatments for gastrointestinal stromal tumors and chronic myeloid leukemia improve because patients can receive tyrosine kinase inhibitor imatinib which finds both BCR-ABL fusion protein and other tyrosine kinases. Traditional administration of imatinib produces a range of negative effects due to systemic toxicity along with resistance development and absorption and solubility limitations. Medical compounds delivered through nanotechnology show promising qualities because they offer both improved targeting precision and better dissolving efficiency and longer drug residence time and reduced side effects. Medical applications of imatinib become stronger when the medication transforms into nanoparticles including liposomes and solid lipid nanoparticles (SLNs) and polymeric nanoparticles and dendrimers and micelles because these mixed nanoparticles decrease treatment side effects. The EPR effect allows the regulation of nanocarrier uptake alongside drug release to achieve improved medicine distribution within tumors. This paper examines contemporary advancements in cancer therapy that employs nanoparticles containing imatinib medication. The research presents diverse nanoparticulate formulations with production techniques together with a detailed explanation of their working mechanisms. The content discusses approaches to create imatinib nanoformulations for advanced cancer therapy through future investigations and how nanoparticles can tackle drug delivery problems.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126027"},"PeriodicalIF":5.2,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775350","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 computational fluid dynamics model for the simulation of flash-boiling flow inside pressurized metered dose inhalers.","authors":"Riccardo Rossi, Ciro Cottini, Andrea Benassi","doi":"10.1016/j.ijpharm.2025.126005","DOIUrl":"10.1016/j.ijpharm.2025.126005","url":null,"abstract":"<p><p>In this work we present, for the first time, a computational fluid dynamics tool for the simulation of the metered discharge in a pressurized metered dose inhaler. The model, based on open-source software, adopts the Volume-Of-Fluid method for the representation of the multiphase flow inside the device and a cavitation model to explicitly account for the onset of flash-boiling upon actuation. Experimental visualizations of the flow inside the device and measurements of the mixture density and liquid and vapor flow rates at the nozzle orifice are employed to validate the model and assess the sensitivity of numerical results to modeling parameters. The results obtained for a standard device geometry show that the model is able to quantitatively predict several aspects of the dynamics and thermodynamics of the metered discharge. We conclude by showing how, by allowing to reproduce and understand the fluid dynamics upstream of the atomizing nozzle, our computational tool enables systematic design and optimization of the actuator geometry.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126005"},"PeriodicalIF":5.2,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784269","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}