Journal of pharmaceutical sciences最新文献

{"title":"Sustained release of betamethasone from solid lipid nanoparticles loaded polymeric hydrogels with natural emollient: One step closer to effective topical therapy for atopic dermatitis","authors":"Tejas Mahesh Athavale ,&nbsp;Maddhusja Nalliah ,&nbsp;Sybil Obuobi ,&nbsp;Øystein Grimstad ,&nbsp;Nataša Škalko-Basnet","doi":"10.1016/j.xphs.2025.103876","DOIUrl":"10.1016/j.xphs.2025.103876","url":null,"abstract":"<div><div>Atopic dermatitis (AD), an inflammatory skin disease, has persisted as a global burden for decades. The existing therapy lacks multitargeted formulations, is ineffective, and bears adverse effects. Consequently, it offers limited relief from pruritus and inflammation, impacting both the patients’ quality of life as well as health care systems. We hypothesize that localized therapy comprising natural emollients offers better therapeutic outcome and superior acceptability. Herewith, we propose the novel hydrogel formulations for multipurpose treatment that utilizes lipid nanoparticles with model drug betamethasone dipropionate (BMS), that are incorporated in gel formulation comprising a natural emollient, coconut oil. BMS-solid lipid nanoparticles (BMS-SLNs), optimized for size and drug load, were embedded in three different hydrogels, all comprising coconut oil as an emollient. Chitosan, alginate, and carbomer were selected as hydrogel-forming material. The nanocarriers-in-hydrogel formulations were evaluated through BMS permeation in human skin as well as their physicochemical properties including viscosity, stability, texture, rheology and pH. Preliminary <em>in vitro</em> and <em>ex vivo</em> studies demonstrated that all hydrogel formulations prolonged BMS release up to 24 h. All formulations were found to be safe as confirmed by <em>in vitro</em> cytotoxicity assay. The novel nanocarrier-in-hydrogel formulations hold promise as an effective therapeutic strategy for AD management.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 8","pages":"Article 103876"},"PeriodicalIF":3.7,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293931","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":"Design and in vitro evaluation of thiolated alginates with N-acetyl-L-cysteine/L-cysteine substructures","authors":"Laura Mackaya-Navarro ,&nbsp;Patrick Knoll ,&nbsp;Víctor H. Campos-Requena ,&nbsp;Paulina I. Hidalgo ,&nbsp;Andreas Bernkop-Schnürch","doi":"10.1016/j.xphs.2025.103872","DOIUrl":"10.1016/j.xphs.2025.103872","url":null,"abstract":"<div><div>A new generation S-protected thiolated alginate was synthesized using a ligand based on l-cysteine ​​protected with <em>N</em>-acetyl-l-cysteine (NACys-Cys) ​​in order to obtain a thiomer with improved mucoadhesive properties. Two types of alginate with different molar mass were evaluated with two ligand concentrations. The successful protection with NACys-Cys was confirmed with FT-IR, NMR and free amino group quantification. Quantification of disulfide and thiol groups showed a maximum of 546.93 ± 58.27 µmol S–S/g polymer and 35.48 ± 1.79 µmol –SH/g polymer. Evaluation of swelling behavior showed a ∼5-fold increase in weight at 2 h in buffer pH 6.8. <em>Ex vivo</em> mucoadhesion tests were performed with porcine intestinal mucosa where the S-protected thiomers remained adhered for an average of 70.9 ± 7.0 h, which was ∼15-fold longer than unmodified alginate (<em>p</em> &lt; 0.0001). Cytotoxicity of S-protected thiomers was evaluated on human colorectal carcinoma cells (Caco-2) by resazurin assay. Both unmodified polymer and thiomers did not show a significant decrease in cell viability (<em>p</em> &gt; 0.05). The results indicate that this novel third-generation S-protected thiomer provides remarkable <em>ex vivo</em> mucoadhesive properties, adequate swelling capacity and no <em>in vitro</em> cytotoxicity. According to results it might be a promising material for medical and pharmaceutical applications.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 8","pages":"Article 103872"},"PeriodicalIF":3.7,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293917","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":"Current and emerging strategies for subcutaneous delivery of high-concentration and high-dose antibody therapeutics.","authors":"Steven Ren","doi":"10.1016/j.xphs.2025.103877","DOIUrl":"https://doi.org/10.1016/j.xphs.2025.103877","url":null,"abstract":"<p><p>Subcutaneous (SC) administration of monoclonal antibodies (mAbs) offers patient-centric benefits such as self-administration, fewer hospital visits, and cost savings. However, developing high-concentration formulations (HCFs, ≥ 100 mg/mL) for SC delivery presents challenges, particularly high viscosity, which affects manufacturability and injectability. This review examines the molecular basis of viscosity in highly concentrated antibody solutions, highlighting the roles of electrostatic and hydrophobic interactions. Key formulation factors, including pH, buffers, sugars, surfactants, and ionic strength are systematically analyzed for their impact on viscosity of antibody solutions. Computational and high-throughput screening tools, including machine learning and biophysical parameters, are explored for early-stage viscosity prediction and candidate selection. Viscosity reduction strategies, including approved and emerging viscosity-reducing agents (VRA) and their synergistic combinations, are comprehensively reviewed. Alternative SC delivery approaches for high-dose antibody therapeutics, such as maximized injection volume, prefilled syringes equipped with shorter ultra-thin wall (UTW) needles or tapered needles, multiple injections per dose, wearable devices, and co-formulation with hyaluronidase, are outlined. Additionally, novel technologies like non-aqueous powder suspensions and large-volume handheld autoinjectors (AI) are discussed, though further development is needed to address usability, bioavailability, and safety concerns. By integrating computational tools, high-throughput screening, diverse viscosity reduction strategies, and alternative delivery solutions, this review provides a structured framework for overcoming high-viscosity and high-dose challenges, facilitating the development of patient-friendly antibody therapeutics for SC administration.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"103877"},"PeriodicalIF":3.7,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293916","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":"Predictive Stability in Biopharmaceuticals and Vaccines: Perspectives and Recommendations Towards Accelerating Patient Access.","authors":"Daniel Skomski, Andrea Ji, Drago Kuzman, Didier Clenet, Aaron Hieb, Scott W Roberts, Joe Berry, Christopher Lentes, Jos Weusten, Kirsten MacArthur, Amy St Charles, Ben Ahlstrom, Sandra Auguste-Bowler, Leanne Chinn, Armin Boehrer, Shaoxin Feng, Chris Thompson, Bernard Francq, Christian Laue, Marie-Eve Bury, Adam Palmer Rauk, Thijs Cui, Matthew Scholfield, Michael Meleties, Yannick Kronimus, Kavitha Jakka, Matjaz Boncina, Pepijn Burgers, Elisabeth Krug, Edgardo Segarra, Jiewei Wu, Cavan Kalonia, Declan Lowney","doi":"10.1016/j.xphs.2025.103873","DOIUrl":"https://doi.org/10.1016/j.xphs.2025.103873","url":null,"abstract":"<p><p>The perspective review discusses predictive stability computational modeling and scientific risk-based approaches to prospectively assess long-term stability and shelf-life of biotherapeutics and vaccines. New regulatory approaches are considered in the context of evolving industry guidelines which are expected to lead to increased usage in clinical trials and market applications. Case studies for many critical quality attributes are broadly covered. Model methodologies, complexities, and mitigations, as well as emerging technologies, are also explained. Outputs of an industry-wide survey elucidate how biopharmaceutical companies are navigating this changing environment. Altogether, it is suggested that predictive stability holds promise for accelerating patient access to new medicines by overcoming stability-related bottlenecks while further enhancing scientific understanding and product robustness.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"103873"},"PeriodicalIF":3.7,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293930","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":"Particle size distribution resolution limit of AAV hs-SV-AUC relative to ls-SV-AUC, mass photometry, and charge-detection mass spectrometry","authors":"Bashkim Kokona ,&nbsp;Austin Vogt ,&nbsp;Neal Whitaker ,&nbsp;Aubree O’Neill ,&nbsp;Kevin D. Ausman ,&nbsp;Jin Wen ,&nbsp;Alfredo Lopez De Leon ,&nbsp;Kimberly A. Malecka ,&nbsp;Thomas A. Laue ,&nbsp;Steven A. Berkowitz ,&nbsp;Sambit R. Kar","doi":"10.1016/j.xphs.2025.103878","DOIUrl":"10.1016/j.xphs.2025.103878","url":null,"abstract":"<div><div>Precise and accurate particle size distributions (PSD) of adeno-associated virus (AAV) preparations are an important measure of sample quality. Particularly challenging is the quantitation of AAV particles carrying genetic payload variants, which are considered impurities that must be minimized. While a plethora of methods exist to evaluate the amount of empty and full AAV particles, quantitation of partially-filled capsids having genomes close to the size of full capsids, has proven more challenging. The recently developed high-speed sedimentation velocity protocol (hs-SV-AUC) provides precise and accurate PSDs quickly. Here we assess the limiting resolution of hs-SV-AUC using both simulated and experimental data for a 1:1 mixture of two purified AAV preparations differing in DNA payloads by 696 nucleotides (NT). As few as 12 absorbance scans are needed to achieve baseline resolution of the two AAV components, while also providing AAV composition information via dual-wavelength analysis. For comparison, PSDs were obtained for the same 1:1 AAV mix using low-speed SV-AUC (ls-SV-AUC), mass photometry (MP) and charge detection mass spectrometry (CD-MS). In terms of their ability to separate the two full AAV peaks, the order of resolution of these methods is as follows: hs-SV-AUC &gt; CD-MS &gt; MP ≈ ls-SV-AUC. The advantages and disadvantages of each method are discussed.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 8","pages":"Article 103878"},"PeriodicalIF":3.7,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293918","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":"Topological indices and data analysis techniques modeling to predict the physicochemical properties of tetracycline antibiotics","authors":"Fateme Movahedi ,&nbsp;Mahsa Zameni ,&nbsp;Mohammad Hadi Akhbari ,&nbsp;Mohammad Hassan Shahavi ,&nbsp;Saeid Rajabnezhad","doi":"10.1016/j.xphs.2025.103871","DOIUrl":"10.1016/j.xphs.2025.103871","url":null,"abstract":"<div><div>The tetracycline family of drugs is one of the most widely used groups of antibiotics in modern medicine. Topological indices act as a bridge between chemistry and mathematics. The Quantitative Structure-Property Relationship (QSPR) models utilize the molecular structure of compounds to predict the physicochemical properties. In this paper, a computational approach was performed using MATLAB coding and decoding to calculate the Sombor-type topological indices of this group of drugs. The linear regression approach has been used in the quantitative model of structure-property relationships to investigate the relationships between Sombor indices and physicochemical properties. This investigation aims to examine the efficacy of topological indices of the Sombor type in predicting the physicochemical properties of tetracycline numerically. The linear regression analysis concluded that the best predictor for H-bond donors, H-bond acceptors, rotatable bonds, and polar surface area is the modified reduced Sombor index, and the increased Sombor index is effective for polarizability and molecular weight. Furthermore, the best predictor of topological indices for refractivity is the Sombor index.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 8","pages":"Article 103871"},"PeriodicalIF":3.7,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285003","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":"Immunogenicity risk mitigation of therapeutic proteins with translational immunogenicity, analytical characterization, and regulatory insight.","authors":"Sadiqua Shadbar, Sathy Balu Iyer, Jared Auclair, Daniel Dadon","doi":"10.1016/j.xphs.2025.103870","DOIUrl":"https://doi.org/10.1016/j.xphs.2025.103870","url":null,"abstract":"<p><p>The immunogenicity of therapeutic proteins remains a key challenge, leading to early and late-stage clinical failures, posing a significant hurdle in the development of safe and efficacious biopharmaceuticals. This review highlights the main categories of factors influencing the immune response-mediated impacts of biotherapeutics: 1) patient-related factors, 2) product-related factors, and 3) administration-related factors. It provides a comprehensive overview of these immune response-mediated impacts, ranging from the development of anti-drug antibody (ADA) responses, injection site reactions (ISR), and injection site pain (ISP). Using immune response-mediated impacts as a focal point, the review discusses tools and strategies that can be used to evaluate the potential critical quality attributes (pCQAs) of therapeutic proteins as they have an impact on immunogenicity. These tools include various immunogenicity assessment assays spanning in silico, in vitro, ex vivo, in vivo animal models, and clinical tools. It also highlights a comprehensive repertoire of analytical characterization methods. Emphasis is placed on the importance of combined stage-appropriate use of these tools to minimize the risk of immunogenicity. Additionally, regulatory guidance, forums, and consortium landscapes are outlined to inform immunogenicity risk assessment strategy for therapeutic proteins. Ultimately, this integrated comprehensive immunogenicity testing strategy aims to advance the field of immunogenicity risk assessment to develop safe and efficacious protein therapeutics.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"103870"},"PeriodicalIF":3.7,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266454","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":"Liposomes containing sorbitan monolaurate incorporated in hydroxyethylcellulose hydrogels for topical delivery of 5-fluorouracil: rheological characterization, skin penetration and cytotoxicity study","authors":"Genuína Stephanie Guimarães Carvalho ,&nbsp;Alice Vitoria Frota Reis ,&nbsp;Luiziana Cavalcante Costa Fernandes Crisóstomo ,&nbsp;Aline Martins dos Santos ,&nbsp;Tamara Gonçalves Araújo ,&nbsp;Marlus Chorilli ,&nbsp;Raquel Petrilli ,&nbsp;Josimar O. Eloy","doi":"10.1016/j.xphs.2025.103868","DOIUrl":"10.1016/j.xphs.2025.103868","url":null,"abstract":"<div><div>In this work, liposomes composed of soy phosphatidylcholine (SPC) and cholesterol (CHOL), in addition to sorbitan monolaurate (span 20), a skin penetration enhancer, were incorporated into hydroxyethylcellulose (HEC) hydrogels to optimize the topical administration of 5-fluorouracil (5-FU) employed in treatment of skin cancer. The formulations were stable (pH, density, viscosity) in the period of 30 days. Furthermore, the pseudoplastic behavior with thixotropy of the developed hydrogels, in the presence or absence of liposomes, was confirmed, proving that liposome incorporation does not compromise their rheological characteristics, maintaining desirable aspects for topical application. Texture and bioadhesion studies also demonstrated the ability of hydrogels associated with liposomes to present good spreadability in parallel with increased contact time of the drug on the skin. Although it was not possible to quantify the active ingredient from the hydrogels, the in vitro release test allowed us to observe a prolonged release of 5-FU by the nanocarriers, which, associated with the polymeric matrix, suggests a system capable of protecting the drug from the physiological environment, while providing effective delivery. Liposomes containing span 20, incorporated into the HEC hydrogel, were capable of delivering 1194,8 ng/cm² of 5-FU into viable epidermis + dermis, observed in the in vitro skin penetration study, unlike samples containing liposomes without span, in which it was not possible to quantify the drug in the skin layers. Therefore, not only we were able to show the potential of span 20 to promote drug skin penetration, but we also proved that with the incorporation of liposomal dispersions in HEC hydrogels, fundamental for enabling their topical application, this property is maintained. Finally, in vitro cytotoxicity evaluated in the A431 cell line provided IC₅₀ values of 1.953 μM, corroborating that hydrogels containing span 20 liposomes containing 5-FU are indeed a promising strategy for potential treatment of skin cancer.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 8","pages":"Article 103868"},"PeriodicalIF":3.7,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266464","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":"Physiologically-based pharmacokinetic modeling of rosuvastatin in Chinese: Predicting the impact of SLCO1B1 and ABCG2 genetic variants and hepatic impairment on drug exposure","authors":"Longjie Li ,&nbsp;Xinyan Zhu ,&nbsp;Wenhang Xu ,&nbsp;Qingfeng He ,&nbsp;Like Xie ,&nbsp;Haishu Lin ,&nbsp;Mengfan Ye ,&nbsp;Paul Chi-Lui Ho ,&nbsp;Juan Xie ,&nbsp;Xiaoqiang Xiang","doi":"10.1016/j.xphs.2025.103866","DOIUrl":"10.1016/j.xphs.2025.103866","url":null,"abstract":"<div><h3>Background</h3><div>Although rosuvastatin is widely prescribed in China, its pharmacokinetic profile shows substantial interindividual variability, primarily due to polymorphisms in drug transporters (<em>SLCO1B1</em> and <em>ABCG2</em>) and variations in hepatic function. Existing physiologically based pharmacokinetic (PBPK) models, primarily developed for Caucasian populations, may lack predictive accuracy in Chinese patients, highlighting the need for population-specific models to support precision dosing.</div></div><div><h3>Method</h3><div>A PBPK model was developed using PK-Sim® software (Version 12.0) and validated using clinical pharmacokinetic data within the 5–20 mg dose range. Key transporter parameters were mechanistically optimized to reflect the functional impacts of <em>SLCO1B1</em> c.521T&gt;C and <em>ABCG2</em> c.421C&gt;A variants. The model was subsequently applied to simulate pharmacokinetic alterations associated with hepatic impairment.</div></div><div><h3>Results</h3><div>The model demonstrated robust predictive performance, with fold errors (FE) for primary pharmacokinetic parameters (T_max, C_max, and AUC_0–t) ranging from 0.54–1.83-fold relative to observed values. The impact of genetic polymorphisms was accurately characterized, with FE values ranging from 0.62- to 1.33-fold. In patients with Child-Pugh class C cirrhosis, systemic exposure (AUC_0–t) increased 3.13–3.16-fold compared with healthy subjects, indicating clinically significant hepatic accumulation.</div></div><div><h3>Conclusion</h3><div>This is the first Chinese-specific PBPK model for rosuvastatin that successfully integrates genetic and hepatic covariates, allowing for the prediction of exposure differences due to <em>SLCO1B1</em>/<em>ABCG2</em> polymorphisms and hepatic impairment. This model provides a valuable tool to guide future clinical dose adjustments in Chinese populations.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 8","pages":"Article 103866"},"PeriodicalIF":3.7,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248407","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":"Higher-order structure comparison of the reference and biosimilar products using spectral distance calculation on the circular dichroism spectra","authors":"Hiroko Shibata ,&nbsp;Taiji Oyama ,&nbsp;Masato Kiyoshi ,&nbsp;Satoko Suzuki ,&nbsp;Yuji Higuchi ,&nbsp;Yoshiro Saito ,&nbsp;Akiko Ishii-Watabe","doi":"10.1016/j.xphs.2025.103865","DOIUrl":"10.1016/j.xphs.2025.103865","url":null,"abstract":"<div><div>A comparative analytical study of the quality attributes of biosimilars and their reference products is an important step in developing biosimilar products. Circular dichroism (CD) spectroscopy is commonly used to demonstrate similarity of higher-order structures. However, in most cases, the similarity of the CD spectra between the reference and biosimilar products is visually determined. Only in a few cases, the fractions of secondary structures (e.g., α-helix and β-strand) estimated from the far-UV/CD spectrum are also compared between the reference and biosimilar products. Therefore, the number of cases in which the CD spectra of the reference product are objectively and numerically compared with those of the biosimilar product is limited. To quantitatively assess the similarity of CD spectra, in this study, we converted the spectra into univariate data, i.e., spectral distances, and applied both the quality range method and the equivalence test to them. These statistical methods were selected based on the recommendation in the U.S. Food and Drug Administration guidance for quantitative quality attributes of high and moderate risk. Application of these method showed that almost all biosimilar products approved in Japan exhibited similarity in CD spectra to each reference product with less than 15 % of the exceptions. Our data indicate that converting the spectra into univariate data allows an objective similarity assessment of higher-order structures between the reference and biosimilar products.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 8","pages":"Article 103865"},"PeriodicalIF":3.7,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248406","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}