Pharmaceutical Research最新文献_第2页

First-in-Class Clinically Investigated Oral Factor D Inhibitors for the Treatment of Complement-Mediated Diseases. 口服因子D抑制剂治疗补体介导性疾病的临床研究

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-06-25 DOI: 10.1007/s11095-025-03882-8

Venkat R Gadhachanda, Jason A Wiles, Steven D Podos, David Boyer, Jane Thanassi, Dhara Patel, Yongsen Zhao, Lijuan Wang, Mingjun Huang

{"title":"First-in-Class Clinically Investigated Oral Factor D Inhibitors for the Treatment of Complement-Mediated Diseases.","authors":"Venkat R Gadhachanda, Jason A Wiles, Steven D Podos, David Boyer, Jane Thanassi, Dhara Patel, Yongsen Zhao, Lijuan Wang, Mingjun Huang","doi":"10.1007/s11095-025-03882-8","DOIUrl":"10.1007/s11095-025-03882-8","url":null,"abstract":"Objective: The goal of the study was to discover small molecular inhibitors of complement factor D (FD), an essential protease for activation of the alternative pathway (AP) of complement, that possess the characteristics for clinical investigation in complement-mediated diseases such as paroxysmal nocturnal hemoglobinuria (PNH).Methods: Compounds were synthesized and tested in vitro for potency, selectivity, and metabolic stability. The optimized compounds were subjected further to a panel of in vitro tests for primary and secondary pharmacology including inhibitory effects on FD, different complement pathways and disease models, as well as to pharmacokinetic and pharmacodynamic evaluations in animals.Results: Following multiple rounds of optimization, danicopan and later vermicopan were chosen as candidates for clinical investigation. Both compounds demonstrated potent and selective inhibitory effects on FD and AP, suitable pharmacokinetic characteristics for oral dosing, and efficacy in PNH in vitro disease models. In addition to enhanced in vitro potency, vemircopan exhibited lower clearance and higher bioavailability in animal studies compared with danicopan.Conclusion: Preclinical evaluations of danicopan and vermicopan provided rationales to conduct clinical studies in complement-mediated diseases. Recently, danicopan was approved as an add-on therapy to the C5 inhibitors ravulizumab or eculizumab for the treatment of extravascular hemolysis in patients with PNH.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497664","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}

引用次数: 0

Quantitative Investigation of Synthetic Mucus Effects on Spray Deposition in a 3D-Printed SLA Nasal Cavity Model. 合成黏液对3d打印SLA鼻腔模型喷雾沉积影响的定量研究。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-06-25 DOI: 10.1007/s11095-025-03886-4

Amr Seifelnasr, Xiuhua April Si, Jinxiang Xi

{"title":"Quantitative Investigation of Synthetic Mucus Effects on Spray Deposition in a 3D-Printed SLA Nasal Cavity Model.","authors":"Amr Seifelnasr, Xiuhua April Si, Jinxiang Xi","doi":"10.1007/s11095-025-03886-4","DOIUrl":"https://doi.org/10.1007/s11095-025-03886-4","url":null,"abstract":"Purpose: To quantify the deposition distribution of intranasally administered sprays in an anatomically accurate 3D-printed nasal model under varying conditions.Methods: A multipiece nasal cast was used to assess deposition under three head positions (upright, 22.5° backward tilt, and 45° backward tilt) and two airflow conditions (no flow and gentle sniff). Synthetic mucus coatings were prepared using saline-based xanthan gum (XG) solutions with two different XG concentrations: 0.25% w/v, representing a healthy state, and 1% w/v, representing a diseased state. Regional doses were quantified using salinity-based measurements for both uncoated and coated nasal casts.Results: The results demonstrate that synthetic mucus coatings significantly altered intranasal spray dosimetry, promoting broader spreading and deeper translocation compared to dry-wall models. In the middle turbinate region, the highest mean deposition occurred under sniff airflow at a 45° backward tilt with a 1% XG coating (76 ppm), representing a 244% increase over the dry condition (22 ppm). For the posterior nasal cavity, the most effective mean deposition was achieved at a 22.5° backward tilt with sniff airflow and a 0.25% XG coating (63 ppm vs. 0 ppm dry). The mucus viscosity can significantly alter regional distribution. A 0.25% XG coating facilitated deeper translocation to the posterior nasal cavity, while 1% XG enhanced retention in the middle turbinate region.Conclusions: These findings highlight the importance of incorporating synthetic mucus in in vitro nasal models to improve physiological relevance and provide insights for optimizing intranasal drug delivery techniques.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497665","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}

引用次数: 0

Efficient Cytosolic Delivery of siRNA Using Lyophilized and Reconstituted Polymer-siRNA Polyplexes. 利用冻干和重组的聚合物-siRNA复合物高效的siRNA细胞质递送。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-06-23 DOI: 10.1007/s11095-025-03884-6

Harini Nagaraj, Taewon Jeon, Yagiz Anil Cicek, Ritabrita Goswami, Nourina Nasim, Rukmini Mhaske, Vincent M Rotello

{"title":"Efficient Cytosolic Delivery of siRNA Using Lyophilized and Reconstituted Polymer-siRNA Polyplexes.","authors":"Harini Nagaraj, Taewon Jeon, Yagiz Anil Cicek, Ritabrita Goswami, Nourina Nasim, Rukmini Mhaske, Vincent M Rotello","doi":"10.1007/s11095-025-03884-6","DOIUrl":"https://doi.org/10.1007/s11095-025-03884-6","url":null,"abstract":"Purpose: siRNA enables highly specific and targeted gene silencing, offering potential treatment for a range of diseases. Cytosolic access of siRNA is essential for efficacy; Current delivery systems generally use endosomal uptake pathways, leading to siRNA degradation due to inefficient escape. Guanidinium functionalized poly(oxanorbornene)imide (PONI) polymers facilitate direct cytosolic siRNA delivery with excellent gene knockdown efficacy in vitro and in vivo. The use of lyophilization to generate stable powders that retain excellent delivery and knockdown activity when reconstituted is demonstrated, providing a key tool for translation.Methods: PONI-Guan polymers were mixed with siRNA to form PONI-Guan/siRNA polyplexes. The generated polyplexes were lyophilized and stored at varying temperature conditions for a total duration of 4 weeks. After reconstitution and delivery, cytosolic access of siRNA was assessed through confocal laser scanning microscopy. Knockdown efficacy was assessed in GFP expressing reporter deGFP HEK 293 T cell line using flow cytometry. Efficacy of reconstituted PONI-Guan/si_STAT3 in 4T1 breast cancer cells was evaluated by quantifying gene expression levels (qRT-PCR) and cell growth inhibition (Alamar blue assay). Delivery and therapeutic efficiency were compared between lyophilized and freshly made polyplexes.Results: Lyophilized polyplexes retained critical functional features of freshly made polyplexes. Resuspended polyplexes facilitated effective cytosolic delivery siRNA and showed therapeutic relevance through the delivery of siRNA targeting STAT-3 gene in 4T1 cells with successful cell growth inhibition (~ 70%) and knockdown (~ 80%) of the gene.Conclusion: Overall, this strategy signifies a highly transferrable and versatile method for effective storage of siRNA.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476294","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}

引用次数: 0

A New Analytical LC-MS/MS Method for Determination of Eight Standard Nitrosamines (NDMA, NMBA, NDEA, NEIPA, NDIPA, NMPA, NDPA, NDBA) in a Commercial Small Molecule Drug Product Capsules and its Active Pharmaeceutical Ingredient for Treatment of Fabry: A Rare Disease. 一种新的LC-MS/MS分析方法测定治疗罕见病法布里病市产小分子制剂胶囊中8种标准亚硝胺（NDMA、NMBA、NDEA、NEIPA、NDIPA、NMPA、NDPA、NDBA）及其活性成分

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-06-17 DOI: 10.1007/s11095-025-03875-7

Krishnaiah Charagondla, Partha S Mukherjee, Kalyani Ginjupalli, Bing Hu, Simrat Kaur, Paresh Thanki, Tejas Tailor, Bhavin Prajapati, Saroj Ramdas

{"title":"A New Analytical LC-MS/MS Method for Determination of Eight Standard Nitrosamines (NDMA, NMBA, NDEA, NEIPA, NDIPA, NMPA, NDPA, NDBA) in a Commercial Small Molecule Drug Product Capsules and its Active Pharmaeceutical Ingredient for Treatment of Fabry: A Rare Disease.","authors":"Krishnaiah Charagondla, Partha S Mukherjee, Kalyani Ginjupalli, Bing Hu, Simrat Kaur, Paresh Thanki, Tejas Tailor, Bhavin Prajapati, Saroj Ramdas","doi":"10.1007/s11095-025-03875-7","DOIUrl":"https://doi.org/10.1007/s11095-025-03875-7","url":null,"abstract":"Purpose: This study aims to develop and validate a highly sensitive LC-MS/MS method for quantifying eight nitrosamine (NA) impurities NDMA, NMBA, NDEA, NEIPA, NDIPA, NMPA, NDPA, and NDBA in a small molecule commercial Active Pharmaceutical Ingredients (API) and Drug Product (DP) capsules used for the treatment of Fabry rare disease in global patients.Methods: The method utilized gradient separation on a C18 column, ensuring optimum resolution between NAs and internal standards. Elution was monitored at precursor and product ions. The method was validated according to ICH Q2 (R1) guidelines, assessing specificity, linearity, recovery, and repeatability in both API and capsule matrices.Results: Quantification of NAs ranged from 0.0215 to 0.780 ppm in relation to a 20.5 mg/mL sample concentration. Linearity coefficients ranged from 0.99 to 1.00. The Detection Limit (DL) was 0.154-0.560 ng/mL, and the Quantitation Limit (QL) was 0.438-1.590 ng/mL. Mean recoveries for all NAs were between 90 and 107%, and repeatability was under 15%. An Analytical Target Profile (ATP) concept was successfully employed to monitor Analytical Method Performance Characteristics (AMPC).Conclusions: The validated LC-MS/MS method proved effective for quantifying NAs (NDMA, NMBA, NDEA, NEIPA, NDIPA, NMPA, NDPA, and NDBA) in both API and capsule matrices, with results consistently below the Quantitation Limit (QL) in confirmatory testing. This approach supports the elimination of routine NA testing, adhering to FDA and EMA's conservative Acceptable Intake (AI) limits, ensuring safety and regulatory compliance for global patients.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317625","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}

引用次数: 0

PEGylation of Propofol Reduces Its Adsorption to Extracorporeal Membrane Oxygenator (ECMO) Components. 异丙酚聚乙二醇化降低其对体外膜氧合器（ECMO）组分的吸附。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-06-05 DOI: 10.1007/s11095-025-03879-3

Benedetta Campara, Nitish Khurana, Andrea De Nadai, Venkata Yellepeddi, Kevin Watt, Gianfranco Pasut, Hamidreza Ghandehari

{"title":"PEGylation of Propofol Reduces Its Adsorption to Extracorporeal Membrane Oxygenator (ECMO) Components.","authors":"Benedetta Campara, Nitish Khurana, Andrea De Nadai, Venkata Yellepeddi, Kevin Watt, Gianfranco Pasut, Hamidreza Ghandehari","doi":"10.1007/s11095-025-03879-3","DOIUrl":"https://doi.org/10.1007/s11095-025-03879-3","url":null,"abstract":"Extracorporeal membrane oxygenation (ECMO) is a life-saving cardiopulmonary bypass technology for critically ill patients. Patients treated with ECMO receive multiple drugs to treat critical illnesses, prevent infections, and maintain sedation. However, inaccurate dosing information of some of the administered drugs is a significant cause of ECMO related mortality. Hydrophobic drugs tend to adsorb on the surface of ECMO circuit components leading to suboptimal dosing and therapeutic failure. Modifying the drugs can be exploited as a strategy to reduce drug adsorption in ECMO circuits. Propofol (Diprivan®) is a widely used anesthetic in ECMO patients that is known to substantially adsorb to ECMO circuit components due to its hydrophobicity. The objective of this work was to evaluate the PEGylation of propofol as a strategy to reduce its adsorption to the ECMO circuit. Poly(ethylene glycol) (PEG) was covalently conjugated to propofol with varying PEG lengths, i.e., 3 monomers of PEG (PEG3), 5 monomers of PEG (PEG5) and 2 kDa molecular weight PEG (PEG2kDa). The conjugates were synthesized, characterized, and compared for their water solubility, ability to spontaneously form micelles, and in reducing adsorption to hydrophobic materials in an in vitro ECMO mimic assay. Further, the conjugates were tested for their anesthetic activity in a C57BL/6 mouse model. We demonstrated that PEG5-Propofol and PEG2kDa-Propofol had improved water solubility and significantly reduced the adsorption of propofol. PEG5-Propofol also demonstrated a similar anesthetic activity (520 ± 109 secs) to free propofol (485 ± 103 secs). Our results demonstrate that PEG5-Propofol is a promising anesthetic for administration to patients on ECMO.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234787","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}

引用次数: 0

Development of Alogliptin Oral-Dissolving Films with Optimized Therapeutic Outcomes. 阿格列汀口服溶出膜的研制及最佳治疗效果。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-06-04 DOI: 10.1007/s11095-025-03873-9

Sagar Pathade, Varsha Balkrishna Mane, Nagesh Aloorkar, Divya Bhagat, Sanuja Kadam, Rushikesh Kshirsagar

{"title":"Development of Alogliptin Oral-Dissolving Films with Optimized Therapeutic Outcomes.","authors":"Sagar Pathade, Varsha Balkrishna Mane, Nagesh Aloorkar, Divya Bhagat, Sanuja Kadam, Rushikesh Kshirsagar","doi":"10.1007/s11095-025-03873-9","DOIUrl":"https://doi.org/10.1007/s11095-025-03873-9","url":null,"abstract":"Introduction: The work aims at formulating Alogliptin benzoate as fast-dissolving film to bypass first-pass metabolism to improve therapeutic benefits.Methods: Alogliptin Oral dissolving films (ODFs) prepared by solvent casting method and physico-chemically characterised. The in vitro dissolution was performed in pH 6.8 phosphate buffer. Accelerated stability studies were conducted.The antidiabetic activity of ODFs was assessed in diabetes-induced Wistar albino rats.Results: The films were found to be slightly translucent, uniform, smooth and flexible in nature. The average weights were found to be 57.87 ± 4.59 mg. Optimized ODFs showed uniformity in drug content of 98.84 ± 2.22% while surface pH was found between 6.87 to 6.93. The FTIR analysis indicated no significant changes in the functional groups of Alogliptin benzoate in optimised formulation. The optimized Alogliptin benzoate ODF formulation shows altered thermal stability and retains the crystalline structure of the drug. Its rod-like crystals and formulation components enhance dissolution, enabling a rapid initial release. While the pure drug dissolves faster initially, ODF demonstrates efficient oral mucosa permeation and quicker blood glucose reduction within the first hour. The drug content in the formulation does not show any significant lowering (98.84 ± 2.22 initial and 96.89 ± 2.12 after 3 month of stability studies).Despite slightly lower glucose levels at 24 h, the ODF F formulation offers improved therapeutic efficiency and controlled release, making it effective for blood glucose management.Conclusion: The Alogliptin benzoate ODF offers a promising alternative for diabetes management, providing rapid onset and improved patient compliance through easier administration.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226276","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}

引用次数: 0

The Next Frontier: Unveiling Novel Approaches for Combating Multidrug-Resistant Bacteria. 下一个前沿：揭示对抗多重耐药细菌的新方法。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-06-01 Epub Date: 2025-06-16 DOI: 10.1007/s11095-025-03871-x

Praveen Mallari, Leila D Rostami, Ida Alanko, Fadak Howaili, Meixin Ran, Kuldeep K Bansal, Jessica M Rosenholm, Outi M H Salo-Ahen

{"title":"The Next Frontier: Unveiling Novel Approaches for Combating Multidrug-Resistant Bacteria.","authors":"Praveen Mallari, Leila D Rostami, Ida Alanko, Fadak Howaili, Meixin Ran, Kuldeep K Bansal, Jessica M Rosenholm, Outi M H Salo-Ahen","doi":"10.1007/s11095-025-03871-x","DOIUrl":"10.1007/s11095-025-03871-x","url":null,"abstract":"Background: The rapid occurrence of bacterial antibiotic resistance poses a significant threat to public health worldwide. Since particularly multidrug-resistant (MDR) pathogens are becoming untreatable with currently available antibiotics, new treatment modalities must be deployed.Objectives: This review explores the recent advancements and the enduring challenges in new antibacterial development for drug-resistant organisms.Results: We describe how bacterial resistance to antibiotics arises and discuss why the traditional drug discovery routes are inefficient. The best alternative strategies to overcome these challenges might include exploring new bacterial pathways, utilizing compounds with antibacterial activities from the human microbiome, and repurposing existing drugs. Moreover, novel drug delivery mechanisms that leverage, for example, nanotechnology-based carriers may be breakthrough ideas that can increase antibiotic efficacy and, at the same time, reduce toxicity. Current clinical trials of next-generation drugs indicate that some treatments possess excellent potential to overcome the MDR issue.Conclusion: Despite the substantial obstacles to getting bench findings to the patient, numerous scientists are still working towards this goal. Both the application of antibiotic stewardship principles and timely considerations through the regulatory pathways are needed to release the next generation of antibiotics that are suitable for the fight against superbugs.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"859-889"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12222395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Critical Needs and Opportunities for Advanced Manufacturing of Lyophilized Injectables. 冻干注射剂先进生产的关键需求和机遇。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-06-01 Epub Date: 2025-06-27 DOI: 10.1007/s11095-025-03869-5

Alina Alexeenko, Maxwell Korang-Yeboah, Serguei Tchessalov

引用次数: 0

Assessment of the Effects of Ionizing Radiation on Biologic Drugs: mAb Product Quality and Risk Evaluation for Global Shipping Logistics. 电离辐射对生物药品影响的评估：全球航运物流单抗产品质量和风险评估。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-06-01 Epub Date: 2025-05-16 DOI: 10.1007/s11095-025-03867-7

Nathalie Fuentes, Arjun Suri, Annette M Medina, Alain Moffett, Aakash Patel, Stanley C Kwok

{"title":"Assessment of the Effects of Ionizing Radiation on Biologic Drugs: mAb Product Quality and Risk Evaluation for Global Shipping Logistics.","authors":"Nathalie Fuentes, Arjun Suri, Annette M Medina, Alain Moffett, Aakash Patel, Stanley C Kwok","doi":"10.1007/s11095-025-03867-7","DOIUrl":"10.1007/s11095-025-03867-7","url":null,"abstract":"Purpose: It is critical to ensure that drug product quality is not negatively impacted after transportation and shipping so that the product remains safe and effective. The traditional shipping validation and product quality assessments focus on factors such as temperature, vibration, shock, agitation, light exposure, and potential contamination. At the same time, due to the complexity of biologics modalities including cell therapy products, the increasing prevalence of non-intrusive inspection (NII) technologies employing ionizing radiation such as X-ray and Gamma rays at security screening at border points has prompted an evaluation of their impact on biologics.Methods: In this study, the effect of X-ray radiation on monoclonal antibody (mAb)-related biologic drug substance and drug products was investigated by subjecting them to worst-case scenario radiation levels, approximately 200 times higher than the recommended dose, within commonly deployed shipping packaging and primary container. Subsequently, product quality attributes, including visible particles, sub-visible particles, purity, and charge variants, were assessed.Results: The results revealed no significant changes in the exposed samples compared to controls, indicating that the mAb-related biologics maintained their product quality despite exposure to heightened X-ray radiation.Conclusions: These findings provide valuable assurance regarding the stability and safety of mAb-related biologics when subjected to X-ray radiation during transportation and security screenings. Our goal is that this work will stimulate further discussion and guidance from drug sponsors and health authorities to evaluate ionizing radiation impact on current biologics and others new modalities to ensure drug and patient safety.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"961-972"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12222358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Innovation Paradox in Emerging Pharmaceutical Markets: Barriers and Opportunities for Sustainable Development. 新兴医药市场的创新悖论：可持续发展的障碍与机遇。

IF 3.5 3区医学

Pharmaceutical Research Pub Date : 2025-06-01 Epub Date: 2025-05-29 DOI: 10.1007/s11095-025-03856-w

Frederico Severino Martins, Sivacharan Kollipara, Praveen Sivadasu, Mingming Yu, Patricia Severino, Eliana Souto

{"title":"The Innovation Paradox in Emerging Pharmaceutical Markets: Barriers and Opportunities for Sustainable Development.","authors":"Frederico Severino Martins, Sivacharan Kollipara, Praveen Sivadasu, Mingming Yu, Patricia Severino, Eliana Souto","doi":"10.1007/s11095-025-03856-w","DOIUrl":"10.1007/s11095-025-03856-w","url":null,"abstract":"Emerging pharmaceutical markets like Brazil, India, and China have seen significant growth due to rising medication demand, expanding middle-class access, and government support. However, this growth often focuses on cost-driven strategies like generic drug production rather than innovation. Challenges such as fragmented regulatory systems, limited infrastructure, low R&D budgets, and dependence on imported active pharmaceutical ingredients (APIs) limit global competitiveness in drug innovation. R&D investment in these markets rarely exceeds 5% of revenue, compared to 20% in established markets, widening the innovation gap. Advanced technologies such as physiologically based pharmacokinetic (PBPK) modeling, artificial intelligence (AI), and virtual bioequivalence studies present opportunities to overcome these barriers. These tools streamline drug development, lower costs, and improve regulatory processes. For instance, a case study on generic donepezil showed that a $150,000 investment in PBPK modeling software could yield returns of 113.7% when clinical studies are required and 1,120% if a biowaiver is granted. These results demonstrate the financial and operational advantages of adopting innovative technologies, enabling faster market entry and scalability across portfolios. By embracing advanced tools, companies in emerging markets can align with global regulatory trends, enhance sustainability through resource efficiency, and improve access to affordable medicines. This approach bridges the gap between economic growth and technological leadership, fostering global competitiveness and contributing to public health advancements.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"1047-1058"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182251","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}

引用次数: 0