European Journal of Pharmaceutics and Biopharmaceutics最新文献

{"title":"Conductive graphene oxide-based hydrogel containing human-like collagen combined with electrical stimulation for wound treatment","authors":"Li Li ,&nbsp;Nan Jiang ,&nbsp;Kai Jia ,&nbsp;Fan Wang ,&nbsp;Jinyao Shang ,&nbsp;Yu Liu","doi":"10.1016/j.ejpb.2025.114806","DOIUrl":"10.1016/j.ejpb.2025.114806","url":null,"abstract":"<div><div>Skin is the largest organ of the human body, it bears the important function of protecting the body. Mechanical injuries destroy the integrity of the skin and make it more vulnerable to infection and injury. Conductive hydrogel is a new biomaterial with high conductivity, good biocompatibility, and high water content, and it has a wide potential for application in the biomedical field. In recent years, the combination of conductive hydrogel and electrical stimulation has attracted widespread attention, but there are few systematic studies in this field. In this paper, graphene oxide (GO) was used as the main conductive body, and reduced graphene oxide (rGO) was obtained by improving the Hummers method to improve the conductivity of hydrogel. Re-adsorbing Human-Like Collagen (HLC), a new composite hydrogel, was prepared by the one-pot method, and its wound repair was evaluated. The hydrogel was reduced in order to obtain a hydrogel with higher conductivity, and the conductivity of the hydrogel reached 1.79 × 10⁻⁴ S/m after 24 h of reduction. <em>In vitro</em> experiments showed that the hydrogel has good antibacterial properties, biocompatibility, hemostasis, and certain promotion of cell growth and migration. The results of the mouse full-thickness skin defect model showed that the wound healing speed of mice treated with conductive hydrogel combined with electrical stimulation was faster than that of mice treated with hydrogel alone. These finding indicate that the prepared conductive hydrogel drug delivery system can be used for promoting wound healing.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114806"},"PeriodicalIF":4.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607814","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":"Sprayable thermosensitive in-situ gels loaded with apoptotic body-integrated nanozymes for improved diabetic wound healing","authors":"Wen Li ,&nbsp;Zihan Zhang ,&nbsp;Biyu Zhou ,&nbsp;Yang Chen ,&nbsp;Weijia Shen ,&nbsp;Naiting Kuai ,&nbsp;Jin Li","doi":"10.1016/j.ejpb.2025.114807","DOIUrl":"10.1016/j.ejpb.2025.114807","url":null,"abstract":"<div><div>Serious vascular dysfunction and recurrent bacterial infection are critical obstacles in diabetic wound healing. Developing novel therapeutic strategies is crucial to address these challenges. Endothelial cell-derived apoptotic bodies (H-Abs), a novel type of extracellular vesicles with anti-inflammation and pro-angiogenesis properties, show great potential for diabetic wound treatment. Herein, a sprayable and thermosensitive in-situ forming composite gel based on poloxamer 407 (P407) was fabricated for the delivery of H-Abs camouflaged manganese dioxide nanozymes (BM), termed BM@H-Abs/TSCG-P407. In vitro and <em>in vivo</em> studies demonstrated that BM@H-Abs/TSCG-P407 undergoes a rapid sol-to-gel transformation in response to wound temperature during spraying treatment, thereby effectively covering irregularly shaped wounds. The incorporated H-Abs-camouflaged BM (BM@H-Abs) can effectively accelerate endothelial cell proliferation and migration, normalize oxygen supply, scavenge reactive oxygen species (ROS) accumulation, inhibit bacterial growth, and eventually enhance the healing of infected wounds in diabetic mice. These results indicate that BM@H-Abs/TSCG-P407 is a promising candidate for the treatment of diabetic wounds.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114807"},"PeriodicalIF":4.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144604619","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":"Stimuli-sensitive hyaluronic acid hydrogels for localized and controlled release of antibodies","authors":"Bita Mahdavi Firouzabadi ,&nbsp;Maria Rosa Gigliobianco ,&nbsp;Dimitrios Agas ,&nbsp;Maria Giovanna Sabbieti ,&nbsp;Claudio Alimenti ,&nbsp;Lakshmi Sathi Devi ,&nbsp;Cristina Casadidio ,&nbsp;Piera Di Martino ,&nbsp;Roberta Censi","doi":"10.1016/j.ejpb.2025.114804","DOIUrl":"10.1016/j.ejpb.2025.114804","url":null,"abstract":"<div><div>Stimuli-sensitive hydrogels are utilized in therapeutic applications for their ability to function as controlled drug delivery systems, particularly as delivery platforms for antibodies in cancer treatment. Their adaptive properties, including biocompatibility, high water retention, and tunable mechanical strength, make them well-suited for local and sustained drug release. In this study, redox-sensitive hydrogels based on thiolated hyaluronic acid (HA-SH) were synthetized as tunable platforms for controlled antibody delivery in cancer therapy. HA-SH hydrogels with different degrees of substitution (DS30, DS50 and DS70) exhibited distinct structural and mechanical properties, with HA-SH DS70 forming a denser network and demonstrating greater stability compared to HA-SH DS30 and DS50. Swelling and degradation studies confirmed redox responsiveness of the gels, with DS30 gel degrading faster than DS50 and DS70 gels in reductive environments. Rheological analysis further showed that higher cross-linking density in DS70 gels enhanced viscosity and mechanical strength compared to DS50 and DS30. Immunoglobulin G (IgG), used as a model drug for immunotherapeutic agents, was loaded into DS30 and DS70 hydrogels. The release followed zero-order kinetics at pH 7.4, highlighting the influence of the polysaccharide intrinsic anionic properties. DS30 hydrogels demonstrated sustained release (85 ± 6 % in 9 days), while DS70 exhibited faster release (71 ± 7 % in 5 days). The IgG release kinetics relied on a dual mechanism involving the combination of gel erosion (depending on DS and structural features), as well as IgG poly-charged nature and its ionic interactions with the hyaluronic acid polymeric network, as highlighted by rheological measurements and differential scanning calorimetry (DSC) analysis. Overall, the study highlights the potential of HA-SH hydrogels as customizable and localized immunotherapeutic delivery systems for controlled and precise cancer treatment.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114804"},"PeriodicalIF":4.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144579360","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":"Quantifying cross-linking strength in sodium starch glycolate and its impact on tablet disintegration and dissolution","authors":"Pauline H.M. Janssen ,&nbsp;Willem Rijpkema ,&nbsp;Kathleen Stout ,&nbsp;Marlijn Orbons ,&nbsp;Arpan Patel ,&nbsp;Bastiaan H.J. Dickhoff","doi":"10.1016/j.ejpb.2025.114803","DOIUrl":"10.1016/j.ejpb.2025.114803","url":null,"abstract":"<div><div>The development of a robust oral solid dosage form requires knowledge of all the sources of variation that could impact the dosage form’s performance and stability, in line with Quality-by-Design (QbD). This requires a deep understanding of the relationships between raw material properties, the process parameters and the final product quality. This paper presents<!--> <!-->a method to quantify the strength of cross-links (SXL) in SSG grades by comparing the sediment volume of precipitation after gelling before and after exposure to alkaline conditions. It is demonstrated that SSG grades with phosphorous cross-links are more resistant to hydrolysis than ester cross-links. The developed method can help formulators to assess the SXL of SSG before use in a formulation. The SXL was quantified for seven marketed SSG grades, showing a clear difference between SSG grades with phosphorous cross-links (SXL ≈ 1) and ester cross-links (SXL 0.4 – 0.7). The tablet disintegration and API dissolution of these SSG grades were evaluated for a wet granulation formulation with atenolol. Results show that all SSG grades with phosphorous cross-links realized 80 % atenolol dissolution within 25 min, whereas all grades with ester cross-links reached this threshold only after 45 min or more. This shows that the type of cross-link is a critical attribute that can result in dissolution success or failure. An excellent correlation was observed between the SXL and the time at which 80 % of the atenolol was dissolved. The findings of this study show that understanding the type of cross-link and the SXL of SSG can support formulators with the development of good, robust formulations, in line with a quality-by-design approach. The provided case study shows that formulators can make their formulations more robust to stress exposure before, during or after tablet manufacturing by using an SSG grade with phosphorous cross-links, thereby limiting the risk of product failure.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114803"},"PeriodicalIF":4.4,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144523547","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 “Liposomal formulations for waterproofing mucosal membranes” [Eur. J. Pharm. Biopharm. 213 (2025) 114757]","authors":"Luisa Coderch ,&nbsp;Lucia Ricci ,&nbsp;Meritxell Martí ,&nbsp;Saman Bagherpour ,&nbsp;Lluïsa Pérez-García ,&nbsp;Cristina Alonso","doi":"10.1016/j.ejpb.2025.114800","DOIUrl":"10.1016/j.ejpb.2025.114800","url":null,"abstract":"","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114800"},"PeriodicalIF":4.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511731","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 and stability evaluation of a pediatric spironolactone oral suspension: Formulation development and analytical validation","authors":"Roxanne Desquines ,&nbsp;Zoubeir Ramjaun ,&nbsp;Acil Jaafar ,&nbsp;Fabien Brouillet ,&nbsp;Sandrine Cavalie ,&nbsp;Thibaut Jamme ,&nbsp;Céline Verdier ,&nbsp;Laurent Cavalie ,&nbsp;Camille Chagneau ,&nbsp;Thomas Lanot ,&nbsp;David Metsu ,&nbsp;Camille Jurado","doi":"10.1016/j.ejpb.2025.114801","DOIUrl":"10.1016/j.ejpb.2025.114801","url":null,"abstract":"<div><div>The pediatric population often faces challenges in accessing appropriate medication formulations, particularly for circumstances like congenital heart disease requiring spironolactone therapy. This study aimed to optimize the pharmaceutical formulation of oral suspension spironolactone for pediatric use and assess its stability. A formulation with 0.2 % xanthan gum in InOrpha® was developed, showing improved stability and reduced sedimentation. Analytical method validation confirmed accuracy and precision for spironolactone quantification, while forced degradation studies ensured stability-indicating capability. Stability assessments demonstrated the oral suspension’s chemical, physical, and microbiological stability for up to 135 days pre-bottle opening and 37 days post-opening under varied storage conditions. This study provides crucial insights into enhancing spironolactone formulation for pediatric patients. Further research is needed to assess pharmacokinetic parameters such as bioavailability and pharmacodynamics to fully ascertain its efficacy in pediatric populations.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114801"},"PeriodicalIF":4.4,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527028","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":"3D-printed hydrogel patch for controlled topical release: Gelatin/tannic acid formulation meets additive manufacturing","authors":"Angélica Graça ,&nbsp;Valeria Tonioli ,&nbsp;Ana M. Martins ,&nbsp;Helena M. Ribeiro ,&nbsp;Joana Marto","doi":"10.1016/j.ejpb.2025.114802","DOIUrl":"10.1016/j.ejpb.2025.114802","url":null,"abstract":"<div><div>Prolonged use of protective masks can cause skin issues like rosacea and “maskne,” particularly among healthcare workers. Poorly fitting commercial dressings often worsen these problems. A novel solution involves 3D-printing personalized hydrogel patches with active ingredients, with customizable designs, concentrations, and controlled release rates.</div><div>This study explores customizable 3D-printed gelatin/ tannic acid hydrogel patches containing metronidazole for rosacea or salicylic acid for maskne treatment. Rheological properties, including gelation temperature, viscosity at gelation temperature, gelation time, and viscosity during printing, were analysed. Optimal printing conditions were determined using a Quality by Design approach with Design of Experiments framework. Three patch designs—occlusive, grid, and triangular infill—were 3D-printed. Mechanical properties were assessed via tensile strength tests, and <em>in vitro</em> studies evaluated the release profiles and permeation of the active ingredients.</div><div>The gelatin/tannic acid and gelatin/tannic acid-metronidazole hydrogels had similar gelation temperatures, while the salicylic acid hydrogel gelled at a lower temperature. All formulations had comparable viscosities at gelation, and gelation times (∼20 s). Optimal print conditions were 42 °C, 25 Psi, and 30 mm/s gelatin/tannic acid and metronidazole hydrogels, and 36 °C and 30 Psi for the salicylic acid formulation. Infill patterns affected mechanical properties and drug release, with grid patterns showing stronger structures and higher drug release rates compared to triangular patterns. <em>In vitro</em> permeation tests revealed salicylic acid penetrated the epidermal barrier and accumulated within the skin, despite low overall retention of both active ingredients.</div><div>These findings highlight the potential of personalized 3D-printed patches for treating mask-related skin conditions.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114802"},"PeriodicalIF":4.4,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144481288","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":"Quaternary ammonium-modified dextran: a unique biodegradable mucoadhesive polymer","authors":"Khush Bakhat Afzal ,&nbsp;Gergely Kali ,&nbsp;Muhammad Haris ,&nbsp;Marlene Ramona Schmidt ,&nbsp;Melanie Ebert ,&nbsp;Eduard Stefan ,&nbsp;Andreas Bernkop-Schnürch","doi":"10.1016/j.ejpb.2025.114788","DOIUrl":"10.1016/j.ejpb.2025.114788","url":null,"abstract":"<div><h3>Aim</h3><div>The present study aims to develop a cationic dextran polymer with improved mucoadhesive properties and high biocompatibility.</div></div><div><h3>Methodology</h3><div>Quaternary ammonium-modified dextran was synthesized of dextran via esterification with N-chlorobetainyl chloride. Structural characterizations like zeta potential measurements, ester quantification, NMR, FTIR, and enzymatic degradation studies were performed to confirm the covalent attachment of quaternary ammonium structure to dextran backbone. Biocompatibility of modified dextran was evaluated by <em>in vitro</em> cytotoxic analysis on HeLa and Caco-2 cells, and hemolysis assay. Furthermore, interaction of modified dextran with porcine mucus was evaluated by using plate rheometer. Mucoadhesive properties were investigated on porcine mucosa mimicking <em>in vivo</em> conditions.</div></div><div><h3>Results</h3><div>A shift in zeta potential from −25.4 ± 0.5 to + 15.6 ± 0.7 mV was obtained for quaternary ammonium-modified dextran with 640.4 ± 9.051 µmol/g ester content. NMR and FTIR analysis confirmed the covalent binding of quaternary ammonium moieties to the polymer backbone. Enzymatic degradation studies demonstrated the lipase-mediated cleavage of quaternary ammonium moieties from modified dextran. Cytotoxicity and hemolysis results proved that quaternary ammonium-modified dextran was not toxic up to the concentration of 0.5 %. Rheometric measurements of quaternary ammonium-modified dextran with mucus showed 2.1- and 3.6-fold higher dynamic viscosity than native polymer at 3 h and 6 h time intervals, respectively. Moreover, compared to native dextran, quaternary ammonium-modified dextran showed 3.4-fold higher mucoadhesive properties on the intestinal mucosa.</div></div><div><h3>Conclusion</h3><div>Because of its cationic character, quaternary ammonium-modified dextran exhibits promising potential as a biodegradable polymer with improved mucoadhesive properties and remarkable biocompatibility.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114788"},"PeriodicalIF":4.4,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144470641","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":"Multimodal in vitro characterization techniques for assessing the adhesion of transdermal patches: A proof-of-concept study","authors":"Sumedha Kapre ,&nbsp;Sushesh Srivatsa Palakurthi ,&nbsp;Mrudul Velhal ,&nbsp;Abhishek Kumar ,&nbsp;Maharshi Thalla ,&nbsp;Susan Immanuel ,&nbsp;Hong Liang ,&nbsp;Srinath Palakurthi","doi":"10.1016/j.ejpb.2025.114783","DOIUrl":"10.1016/j.ejpb.2025.114783","url":null,"abstract":"<div><div>Adhesion is a critical factor in determining the quality, efficacy, and safety of transdermal patches. The adhesive properties directly influence drug permeation and flux, especially for matrix system patches. For potent therapeutics, the strength of adhesion and any minor tampering during wear can significantly impact the patch’s <em>in vivo</em> performance. Adhesive properties can vary over time due to changes in polymer interactions, with storage-induced three-dimensional alterations potentially affecting both adhesive strength and drug characteristics. Despite these complexities, no standardized method currently exists for measuring adhesive strength in transdermal patches. Therefore, reliable and consistent testing methods are essential to ensure patch quality and therapeutic efficacy. This study presents a multimodal approach to assess the adhesion of transdermal patches, incorporating traditional probe-tack and <em>in vitro</em> permeation tests, along with innovative techniques such as interferometry for surface topography analysis and infrared thermography to evaluate structural and adhesive deficiencies. The feasibility of these methods was validated by tampering fresh and expired patches across multiple rounds (2R, 5R, 10R). Validation was confirmed by measuring patch thickness before and after tampering with digital calipers, quantifying removed drug, and analyzing patch roughness and topography via interferometry. Adhesive performance was further assessed using the probe-tack test, while nicotine permeation profiles (both intact and tampered) were evaluated using vertical Franz diffusion cells. Statistical analysis, including one-way ANOVA and Tukey’s post-hoc test, identified significant differences between the datasets. The study utilized two different brands of 14 mg nicotine patches as models. Results indicated that the reference patches exhibited superior adhesive performance and uniform distribution compared to the test patches. The data demonstrates the potential of thermal imaging and interferometry as complementary techniques to distinguish adhesive performance differences in Q2-equivalent transdermal patches produced by different manufacturers.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114783"},"PeriodicalIF":4.4,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474435","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 impact of ionic excipients on stabilization of enalapril tablets by the formation of alkaline salt “in situ”","authors":"Aleš Franc ,&nbsp;Bořek Žaludek ,&nbsp;Petr Sova ,&nbsp;Roman Goněc ,&nbsp;Jan Muselík","doi":"10.1016/j.ejpb.2025.114790","DOIUrl":"10.1016/j.ejpb.2025.114790","url":null,"abstract":"<div><div>The formation of salts is one of the possibilities of stabilizing medicinal substances. Salts can be prepared during the manufacture of the dosage form, saving time, reducing cost and environmental impact. Several studies have documented significant enalapril maleate (EM) instability. EM decomposes into diketopiperazine (DKP) and diacid (DA) impurities at elevated temperature and humidity. Notably, toxic DKP is preferentially formed at pH 2 – 3, and DA formation dominates at pH values above 5. This instability raises concerns about the therapeutic efficacy and safety of the drug. The proposed stabilization strategy involves the “in situ” conversion of EM into a stable sodium salt. This is achieved by incorporating suitable ionic excipients, specifically alkali metal salts and an ethanol-based hydrolysis inhibitor, into the granulation solution. This method effectively inhibits the deethylation to DA and provides uniform tablets with minimal DKP content to ensure long-term five-year stability. In general, these tablets show a lower content of degradation products compared to the stability results reported so far in various generics, and the amount of impurities meets the ICH Q3B (R2) requirements.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"214 ","pages":"Article 114790"},"PeriodicalIF":4.4,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144368724","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}