Journal of Pharmaceutical Innovation最新文献

{"title":"Graphene Oxide Nanosheets Incorporated Jasmine Floral Wax and Castor Oil-Based Thermoreversible Oleogel for Improved Corneal Permeation of Ketoconazole: In-vitro-ex-vivo Characterization and Antifungal Study","authors":"Sopan Nangare,&nbsp;Mahesh Girase,&nbsp;Prashant Patil,&nbsp;Ganesh Patil","doi":"10.1007/s12247-025-09982-7","DOIUrl":"10.1007/s12247-025-09982-7","url":null,"abstract":"<div><p>The targeted delivery of drugs to ocular tissue has garnered significant attention for treating ocular diseases. Traditional ophthalmic formulations have various drawbacks, such as low absorption, limited corneal permeation, and rapid removal of the dosage from the ocular cavity. Recently, the scientific community has shown interest in using oleogels for managing ocular infections, although there is a prerequisite for further enhancement in corneal permeation. Graphene oxide (GO) has gained significant attention in drug delivery due to its excellent biocompatibility, aptitude to enhance permeation, and surface tunability. In this research work, we developed an oleogel based on GO, jasmine floral wax (JFW), and castor oil (CO) to improve corneal permeation for targeted delivery of ketoconazole (KTZ). In brief, the prepared GO-KTZ-JFW/CO oleogel underwent various spectral characterizations, antifungal studies, in vitro release assessments, ex vivo permeation experiments, etc. The obtained results revealed that the GO-KTZ-JFW/CO oleogel exhibited good antifungal activity against <i>Candida albicans</i>, attributed to the combination of GO and KTZ. Furthermore, in vitro studies confirmed that 66.33 ± 1.88% of KTZ was released within 6 h (best-fit model: Korsmeyer peppas; 0.991), following a non-Fickian diffusion mechanism (<i>n</i> = 0.554) in oleogels. Notably, the GO-KTZ-JFW/CO oleogel (batch: JC5) significantly improved the ex vivo permeation of KTZ molecules through the caprine cornea. Therefore, this study highlights the presence of GO in oleogels contributes to the enhancement of trans-corneal permeation of KTZ. In conclusion, the GO-KTZ-JFW/CO oleogel demonstrates improved corneal permeation of KTZ and good antifungal ability, marking a potential avenue for ophthalmic oleogels.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"20 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143769779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formulation and Evaluation of Immediate-Release Quetiapine Fumarate Tablets Via Twin-Screw Melt Granulation","authors":"Salonee Chavan,&nbsp;Siva Ram Munnangi,&nbsp;Nagarjuna Narala,&nbsp;Sateesh Kumar Vemula,&nbsp;Michael Repka","doi":"10.1007/s12247-025-09981-8","DOIUrl":"10.1007/s12247-025-09981-8","url":null,"abstract":"<div><h3>Purpose</h3><p>This study aimed to develop immediate-release Quetiapine Fumarate (QTF) tablets using twin-screw melt granulation (TSMG), a solvent-free and efficient granulation method, and compare their dissolution profiles with the marketed product.</p><h3>Methods</h3><p>QTF tablets were formulated using TSMG with varying concentrations of Ludiflash^® as a diluent and HPMC as a binder. Granules were prepared using a twin-screw extruder at 150 °C, optimized for feed rate and screw design. Granules were characterized for flow properties, thermal stability, and molecular interactions using differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy. Compressed tablets were evaluated for weight variation, hardness, friability, disintegration, and dissolution. Drug release profiles were compared with a commercial product.</p><h3>Results</h3><p>TSMG improved granule flow properties, with all formulations exhibiting excellent post-extrusion characteristics. DSC confirmed the retention of QTF crystallinity, and FTIR demonstrated excipient compatibility. The tablets passed pharmacopeial tests for weight variation, hardness, friability, and disintegration. Dissolution studies showed that formulations F4, F5, and F6 released over 85% of the drug within 15 min, comparable to the marketed product.</p><h3>Conclusion</h3><p>TSMG is a robust and cost-effective technology for manufacturing immediate-release QTF tablets. The solvent-free process ensures compatibility, thermal stability, and rapid drug release, making TSMG a promising alternative for continuous pharmaceutical production.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"20 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12247-025-09981-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143761795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and Predictive Analysis of Revenue Determinants in the Pharma Industry: A Longitudinal Analysis of Financial, Regulatory and Pipeline Data","authors":"Rusne Sipelyte,&nbsp;Athina Marina Metaxa","doi":"10.1007/s12247-025-09975-6","DOIUrl":"10.1007/s12247-025-09975-6","url":null,"abstract":"<div><h3>Purpose</h3><p>Maintaining positive revenue performance and R&amp;D productivity is crucial for the pharma industry, therefore identifying and predicting future revenue determinants is of upmost importance. The aim of the study was to identify factors that determine annual revenue and to use these factors to develop a model that predicts future revenues.</p><h3>Methods</h3><p>IDEA Pharma’s longitudinal Pharmaceutical Innovation and Invention Index data were used to conduct the analyses, looking at the financial, regulatory and pipeline data (2019–2023) of the top 24 pharmaceutical companies. Broader industry trends over the last 5 years were analysed using descriptive statistics. To validate the factors gleaned from the descriptive statistics, a predictive model was constructed. This was done through predictive statistical analysis (stepwise regression), producing a model that can predict future revenue.</p><h3>Results</h3><p>Three factors were determined to be significant determinants of higher future revenues: higher R&amp;D spend, lower R&amp;D spend as a proportion of current revenue, and higher number of Phase III clinical trials.</p><h3>Conclusions</h3><p>The resulting model combined financial, commercial, and strategic metrics from the world’s largest pharmaceutical companies to produce a statistically robust method of predicting revenues, that is critical for every pharma company’s growth and strategic planning.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"20 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12247-025-09975-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell and Gene Therapy Products: Navigating the Regulatory Landscape of Paradigm Approvals in the US (2020 to 2024)","authors":"Ankita Arun Tandulje,&nbsp;Priya Changdev Varpe,&nbsp;Purva Dayanand Chaugule,&nbsp;Sneha Saji,&nbsp;Fathima Nizar,&nbsp;Rajeev Singh Raghuvanshi,&nbsp;Saurabh Srivastava","doi":"10.1007/s12247-025-09973-8","DOIUrl":"10.1007/s12247-025-09973-8","url":null,"abstract":"<div><h3>Purpose</h3><p>The purpose of this research is to analyze regulatory approvals of Cell and Gene Therapy Products by the FDA from 2020 to 2024. The study aims to explore the utilization of expedited regulatory pathways, including RMAT designation, and their impact on the approval trends of cell and gene therapies. Additionally, the research investigates therapeutic area-specific trends and highlights the significance of advanced Therapies in addressing unmet medical needs.</p><h3>Methods</h3><p>Data on FDA-approved Cell and Gene Therapies (2020–2024) were sourced from the FDA's public database. Approvals were analyzed by regulatory designations and therapeutic areas, with a focus on RMAT designation, introduced in 2016 to expedite advanced therapy approvals.</p><h3>Results</h3><p>Between 2020 and 2024, the FDA approved 25 Cell and Gene Therapy products, with 36% approved in 2024. The majority (34%) received Orphan Drug designation, followed by Breakthrough Therapy (20%) and RMAT (16%). Oncology led with 31% of approvals. RMAT requests and approvals increased, reaching a 70.7% approval rate in 2024, reflecting improved submission quality and regulatory alignment. These trends highlight the FDA's focus on innovation while maintaining safety and efficacy standards.</p><h3>Conclusion</h3><p>Between 2020 and 2024, 25 ATMPs were approved in the US, showcasing advancements in regenerative medicine, particularly in oncology and rare diseases. Expedited pathways like RMAT, Breakthrough Therapy, and Orphan Drug designations accelerated access while ensuring safety. These trends underscore the role of adaptive regulatory frameworks in driving innovation and addressing critical unmet needs, paving the way for future breakthroughs.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"20 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Innovation Accelerates into the Future","authors":"Stephen Scypinski","doi":"10.1007/s12247-025-09958-7","DOIUrl":"10.1007/s12247-025-09958-7","url":null,"abstract":"","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"20 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First Time Exploration of Few Novel Molecules from Oxidative Degradation of Raw and Tableted Quetiapine and Unveiling Their Toxico-Pharmacological Potentials for Future Drug Discovery","authors":"Dipanwita Bera,&nbsp;Darakhshan Begum,&nbsp;Balaram Ghosh,&nbsp;Susmita Mallick,&nbsp;Souvik Basak,&nbsp;Nandagopal Sahoo","doi":"10.1007/s12247-025-09968-5","DOIUrl":"10.1007/s12247-025-09968-5","url":null,"abstract":"<div><h3>Purpose</h3><p>Quetiapine (QUE) is an FDA approved antimanic and antischizophrenic active pharmaceutical ingredient (API). However, quetiapine is disseminated worldwide in tablets requiring special attention regarding its stability on storage. Also, as per the official compendium, a maximum ± 10% of such impure or degradation products is allowed in the API as well in tablets. Hence isolation, explicit characterization and toxicological profiling of such products become pertinent. In addition, recycling opportunity of such products into newer bioactive molecules need to be explored in the realm of drug discovery and circular economy.</p><h3>Methods</h3><p>Acid, base, oxidative, photolytic and thermal degradation pathways are explored first by subjecting QUE to respective conditions. The products were subsequently analyzedby HPLC. Finally, oxidative pathway was chosen for investigation to isolate and characterize the degradation products. Toxicological studies and in vitro antimicrobial activity investigations were undertaken with the obtained degradation products.</p><h3>Results</h3><p>Characterizations revealed, the 3-oxo hydroxyl ethyl chain, two side phenyl rings, the two α-carbon atoms adjacent to piperazine nitrogens and the Sulphur of the central thiazepine ring, have been the most susceptible positions for the oxidation. Different novel degradation products have been obtained from QUE API and QUE tablets. Interestingly, certain degradation products revealed considerable in vitro antimicrobial activity. Mild allergic manifestations were observed afterthe degradation products had been tested on rodents. An overall in silico studies revealed a few adverse effects on human organs.</p><h3>Conclusion</h3><p>Molecules explored from our QUE degradation have been novel till date, providing potential scaffolds for novel antimicrobial agents. The degradation products also insinuated a few adverse effects for drug manufacturers. Above all, this is maiden report on investigations of QUE tablet degradation.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"20 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143716978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of the Synergistic Antibacterial Properties of a Gel Formulated from Green-Synthesized Chitosan-Coated Copper Oxide Nanocomposite","authors":"Swapna Paul,&nbsp;M. K. Deepa","doi":"10.1007/s12247-025-09933-2","DOIUrl":"10.1007/s12247-025-09933-2","url":null,"abstract":"<div><h3>Purpose</h3><p>Pathogenic bacteria are responsible for the increase of infectious diseases throughout the world, and the development of next-generation drugs is severely hampered by the resistance of pathogenic microorganisms to drugs. Therefore, research is urgently focusing on the development of novel antimicrobial agents using biopolymers or drug-coated nanobiomaterials called nanoantibiotics. The CS-coated CuO NPs could be used to treat microbiological diseases. Additionally, this study aims to formulate these antimicrobial agents into a gel dosage form to enhance their application in treating infections effectively.</p><h3>Methods</h3><p>This research focuses on the investigation of the synergistic antibacterial properties of a gel formulated from green-synthesized chitosan-coated copper oxide nanocomposite. The zeta potential, particle size distribution, X-ray diffraction (XRD), UV–visible spectroscopy, FE-SEM and EDS were used to evaluate the green synthesised nanocomposite. The minimum inhibitory concentration (MIC) of the nanocomposite against Gram-positive and Gram-negative bacteria was determined by the broth dilution method. The optimised nanocomposite was used in the development of an antibacterial gel with different carbopol concentrations. The pH, viscosity, spreadability and extrudahility of each formulation were also evaluated. The synergy in this work comes from harnessing the powerful antibacterial effects of copper oxide with the biocompatible, film-forming properties of chitosan, providing an effective defense against antibiotic-resistant bacteria.</p><h3>Results</h3><p>Chitosan-coated copper oxide nanoparticles (CS-CuO) showed an absorption maximam in the visible region at 437 nm XRD data revealed characteristic diffraction patterns of the phases. The FE-SEM image of the synthesized nanocomposite showed spherical shape and size between 52.73 nm and 64.45 nm. The average particle size was 272.4621.52 nm. The poly dispersion index and zeta potential were 0.946 and 27/5.95 respectively. The optimized formulation showed acceptable physical properties in terms of color, homogeneity. consistency, spreadability. The result of the synergistic effect in this work demonstrates enhanced antibacterial activity of the gel formulated with green-synthesized chitosan-coated copper oxide nanocomposites.</p><h3>Conclusion</h3><p>The synthesized CS-CuO nanocomposite gel is effective in topical application and has antibacterial properties. Among the different formulations tested, the best formulation is the one that optimally balances pH, viscosity, spreadability, and extrudability, ensuring maximum antibacterial activity and ease of use. Specifically, a formulation with an appropriate concentration of Carbopol 934 that provides these characteristics while maintaining the stability and efficacy of the nanocomposite would be considered the best.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"20 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143716977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of Chitosan-Based Microencapsulation System for Mitragyna speciosa Alkaloids: A Novel Approach for Alzheimer’s Disease Treatment","authors":"Parichat Thepthong,&nbsp;Sirirat Srirat,&nbsp;Wanrudee Hiranrat,&nbsp;Panita Kongsune,&nbsp;Netnapa Chana","doi":"10.1007/s12247-025-09977-4","DOIUrl":"10.1007/s12247-025-09977-4","url":null,"abstract":"<div><h3>Purpose</h3><p>We developed a novel chitosan-based microencapsulation system for <i>Mitragyna speciosa</i> alkaloids to enhance their therapeutic potential in Alzheimer’s disease (AD) treatment, focusing on cholinesterase inhibition and antioxidant properties.</p><h3>Methods</h3><p>Three <i>M. speciosa</i> strains were fractionated and evaluated for anti-cholinesterase activity, antioxidant properties, and mitragynine content using HPLC analysis. The optimal fraction was encapsulated in chitosan microparticles using ionic gelation. The formulation was characterized for morphology, particle size, zeta potential, and encapsulation efficiency. Release kinetics and maintained biological activity were assessed through simulated gastrointestinal digestion.</p><h3>Results</h3><p>The alkaloid fraction from green-veined variety (MAG) exhibited superior acetylcholinesterase (IC₅₀: 70.17 ± 0.98 µg/mL) and butyrylcholinesterase inhibition (IC₅₀: 54.39 ± 5.43 µg/mL), correlating with its highest mitragynine content. MAG-loaded chitosan microparticles demonstrated optimal characteristics with uniform spherical morphology (diameter: 665.9 ± 16.5 nm, PDI: 0.369 ± 0.006), high stability (zeta potential: +57.11 ± 3.15 mV), and efficient encapsulation (72.60 ± 0.25%). The formulation showed controlled release under simulated gastrointestinal conditions while maintaining anti-cholinesterase activity.</p><h3>Conclusions</h3><p>This study presents an effective microencapsulation strategy for enhancing the therapeutic potential of <i>M. speciosa</i> alkaloids. The optimized formulation demonstrates improved stability and controlled release properties, offering a promising approach for AD treatment through sustained biological activities.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"20 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12247-025-09977-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, Development and Evaluation of Polyherbal Lollipops Formulation for the Treatment of Oral Thrush and Periodontal Disease","authors":"Rushikesh Kshirsagar,&nbsp;Varsha Balkrishna Mane,&nbsp;Nagesh Aloorkar,&nbsp;Divya Bhagat,&nbsp;Sanuja Kadam,&nbsp;Sagar Pathade","doi":"10.1007/s12247-025-09970-x","DOIUrl":"10.1007/s12247-025-09970-x","url":null,"abstract":"<div><h3>Purpose</h3><p>The present investigation aims to formulate a polyherbal lollipops incorporating Neem (<i>Azadirachta indica</i>), Clove (<i>Syzygium aromaticum</i>), Ginger (<i>Zingiber officinale</i>) extract to combat dental problems of Oral Thrush and Periodontal Disease.</p><h3>Methods</h3><p>Such lollipops were successfully prepared by using heating and congealing method using 23 full factorial design approach. Sucrose, Methyl Cellulose and corn syrup were considered as independent variables and their effect was studied on Hardness, drug release and disintegration time considering as a dependent variable.</p><h3>Result</h3><p>The optimized formulation was found to be symmetrical, smooth, and clear with shiny surfaces and no inconsistencies. The hardness and disintegration time of formulation with increasing concentration ranges between 6 (Kg/cm.sq) -14 (Kg/cm.sq) and 7.56 min to 14.11 min. whereas the drug release was found in between 25.34 ± 2.3% to 89.01 ± 1.9%. After evaluating formulation it has been found that level of independent variables positively affects the Hardness and disintegration time while negatively affects drug release.</p><h3>Conclusion</h3><p>The formulation showed enhanced antifungal (<i>candida albicans</i>) and anti-bacterial (<i>streptococcus mutans</i>) activities when compared with standard drugs of Ketoconazole and Erythromycin respectively.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"20 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12247-025-09970-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Tolerance-based Approach for Validating Analytical Methods Using Design of Experiments","authors":"Gule Teri,&nbsp;Timothy Eveleigh","doi":"10.1007/s12247-025-09953-y","DOIUrl":"10.1007/s12247-025-09953-y","url":null,"abstract":"<div><h3>Purpose</h3><p>Statistically reliable analytical method validation is essential in pharmaceutical manufacturing to ensure accurate and reproducible test results, supporting quality assurance, regulatory compliance, and consistent production. However, traditional validation techniques often overlook dataset variations relative to the assay range or specification limits, potentially compromising assay fit-for-purpose, particularly for low concentrations of active pharmaceutical ingredients (APIs), excipients, or impurities. This study aims to address these limitations by developing and applying a tolerance-based design of experiments (DOE) approach for validating analytical methods, with a focus on polyethyleneimine (PEI), an impurity associated with lentiviral vector drug products.</p><h3>Methods</h3><p>The tolerance-based DOE approach identifies optimal experimental designs with minimal sample sizes, considering variability relative to tolerance or design margins rather than average values. An analytical method was validated using high-performance liquid chromatography (HPLC) to assess the accuracy, repeatability, and intermediate precision for low-concentration components. This novel framework was compared against traditional validation methods to evaluate its effectiveness.</p><h3>Results</h3><p>The tolerance-based approach corrected misinterpreted results for accuracy, repeatability, and intermediate precision, which are often skewed in traditional methods by calculations based on incorrect scales or averages. By measuring variability relative to tolerance limits, the method provides a more accurate reflection of data variations, enhancing the fitness-for-use of the assay. These results support more informed decision-making and ensure reliability and accuracy across the validation process.</p><h3>Conclusion</h3><p>This study demonstrates that a tolerance-based DOE approach effectively overcomes the limitations of traditional validation methods. By correctly analyzing and presenting accuracy and precision, this method enhances quality control processes and ensures the consistent production of safe and effective pharmaceutical products, offering significant advancements in validation practices, particularly for low-concentration analyses.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"20 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}