Pharmaceutical Research最新文献

{"title":"GraphDeep-hERG: Graph Neural Network PharmacoAnalytics for Assessing hERG-Related Cardiotoxicity.","authors":"Yankang Jing, Yiyang Zhang, Guangyi Zhao, Terence McGuire, Jack Zhao, Ben Gibbs, Ganqian Hou, Zhiwei Feng, Ying Xue, Xiang-Qun Xie","doi":"10.1007/s11095-025-03848-w","DOIUrl":"10.1007/s11095-025-03848-w","url":null,"abstract":"<p><strong>Purpose: </strong>The human Ether-a-go-go Related-Gene (hERG) encodes rectifying potassium channels that play a significant role during action potential repolarization of cardiomyocytes. Blockade of the hERG channel by off-target drugs can lead to long QT syndrome, significantly increasing the risk of proarrhythmic cardiotoxicity. Traditional hERG screening methods are effort-demanding and time-consuming. Thus, it is essential to develop computational methods to utilize the existing knowledge for faster and more accurate in silico screening. Although with wide use of deep learning/machine learning algorithms, existing computational models often rely on manually defined atomic features to represent atom nodes, which may overlook critical underlying information. Thus, we want to provide a new method to learn the atom representation automatically.</p><p><strong>Methods: </strong>We first developed an automated atom embedding model using deep neural networks (DNNs), trained with 118,312 compounds collected from the ZINC database. We then trained a Graph neural networks (GNNs) model with 7909 ChEMBL compounds as the classifying part. The integration of our atom embedding model and GNN models formed a classifier that could effectively distinguish between hERG inhibitors and non-inhibitors.</p><p><strong>Results: </strong>Our atom embedding model achieved 0.93 accuracy in representing structures. Our best GNN model achieved an accuracy of 0.84 and outcompeted traditional machine-learning models, as well as published AI-driven models, in external testing.</p><p><strong>Conclusions: </strong>These results highlight the potential of our automated atom embedding model as a standard for generating robust molecular representations. Its integration with advanced GNN algorithms offers promising assistance for screening hERG inhibitors and accelerating drug discovery and repurposing.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"579-591"},"PeriodicalIF":3.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720968","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":"An In Vitro Dissolution Method for Inhaled Drugs Depositing in the Tracheobronchial Lung Region.","authors":"Alexander Huang, Scott Tavernini, Dino J Farina, Warren H Finlay, Andrew R Martin","doi":"10.1007/s11095-025-03860-0","DOIUrl":"https://doi.org/10.1007/s11095-025-03860-0","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate and develop a novel dissolution test method using tracheobronchial (TB) mimic filters for assessing the dissolution behavior of inhaled drugs targeting the tracheobronchial lung region.</p><p><strong>Methods: </strong>Fluticasone propionate (FP), a poorly soluble corticosteroid, was selected as the test drug. A novel filter-based apparatus (FBA) fractionated the inhaled dose into extrathoracic, tracheobronchial, and alveolar fractions. FP was delivered via dry powder inhaler (DPI) (Flovent Diskus, 250 µg) and pressurized metered-dose inhaler (pMDI) (Flovent HFA, 250 µg). Regional deposition estimates were compared between inhalers. Dissolution tests were performed on the captured TB dose using phosphate-buffered saline + 0.5% sodium dodecyl sulfate at 37 °C. First-order dissolution rate constants ( <math><msub><mi>k</mi> <mn>1</mn></msub> </math> ), difference ( <math><msub><mi>f</mi> <mn>1</mn></msub> </math> ), and similarity ( <math><msub><mi>f</mi> <mn>2</mn></msub> </math> ) factors were calculated. Particle distribution and loading effects on the TB filter were assessed using scanning electron microscopy (SEM).</p><p><strong>Results: </strong>The TB filter demonstrated consistent performance, with no drug loading effects observed for up to the highest drug loading tested, which was 7 actuations of the DPI (~ 110 µg FP collected on the TB filter), or 5 actuations of the pMDI (~ 170 µg). Dissolution profiles revealed no significant differences across DPI doses, and slower dissolution rates for the pMDI compared to the DPI, with <math><msub><mi>k</mi> <mn>1</mn></msub> </math> values indicating significant differences (p < 0.05). SEM showed no particle aggregation or filter clogging. Similarity and difference factors supported these findings.</p><p><strong>Conclusions: </strong>The dissolution method discriminated between the two inhalers and is a promising new tool for use in the dissolution testing of orally inhaled drug products.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":"42 4","pages":"639-650"},"PeriodicalIF":3.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009254","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":"Nitrosamine Drug Substance-Related Impurities (NDSRIs) in Pharmaceuticals: Formation, Mitigation Strategies, and Emphasis on Mutagenicity Risks.","authors":"Dande Aishwarya, Vaishnavi Ramakant Dhampalwar, Nikhil Pallaprolu, Ramalingam Peraman","doi":"10.1007/s11095-025-03857-9","DOIUrl":"https://doi.org/10.1007/s11095-025-03857-9","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the formation, detection, mutagenicity, and control strategies of nitrosamine drug substance-related impurities (NDSRIs) in pharmaceutical formulations, emphasizing regulatory compliance, risk mitigation, and the establishment of acceptable intake (AI) limits for enhanced drug safety.</p><p><strong>Methods: </strong>This study reviews the NDSRI formation and mutagenicity assessment methods, including in silico, in vitro, and in vivo assays. It also explores mitigation strategies and approaches for determining AI limits.</p><p><strong>Results: </strong>The findings indicate that NDSRIs are primarily formed through the nitrosation of APIs containing amine groups, with key risk factors including reactive functional groups and interactions between drugs and excipients. Mutagenicity evaluation revealed that while in silico and in vitro assays provide initial insights, in vivo assays offer more comprehensive and biologically relevant data by capturing complex metabolic processes and systemic interactions. Effective mitigation strategies, such as optimizing the manufacturing conditions and using nitrosation inhibitors, are crucial in reducing NDSRI formation. Approaches like the carcinogenic potency categorization (CPCA) and read-across methods are proposed for determining AI limits, facilitating safer exposure thresholds and supporting regulatory compliance.</p><p><strong>Conclusion: </strong>A multifaceted approach is vital for managing NDSRIs in pharmaceuticals. Comprehensive mutagenicity testing, especially in vivo assays, provides biologically relevant insights into NDSRI-associated risks. Implementing control strategies and, determining AI limits are key to minimizing exposure. Strengthening regulatory frameworks and industry practices improves drug safety, quality, and public health protection.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":"42 4","pages":"547-578"},"PeriodicalIF":3.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006028","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":"Characterizing the Influence of Relative Humidity and Ethanol Content on the Dynamic Size Distributions of Aerosols Generated from a Soft Mist Inhaler.","authors":"Yiliang Lance Jiang, Jose R Ruiz, Richard Friend, Jonathan P Reid","doi":"10.1007/s11095-025-03851-1","DOIUrl":"10.1007/s11095-025-03851-1","url":null,"abstract":"<p><strong>Objective: </strong>Inhaled drug delivery systems need to ensure that the delivered aerosol effectively reach the lungs while overcoming challenges related to environmental conditions, such as relative humidity (RH). This study investigates the impact of environmental factors on aqueous aerosol behaviour using a Respimat® Soft Mist Inhaler (SMI) formulated with and without ethanol content.</p><p><strong>Methods: </strong>Comparative Hygroscopic Aerosol Particle Sizing (CHAPS) was used to measure aerosol size distribution under varying RH levels, while single droplet analysis was conducted using Comparative Kinetics-Electrodynamic Balance (CK-EDB) to assess particle behaviour.</p><p><strong>Results: </strong>The findings reveal that increased RH results in larger particle sizes, while elevated ethanol content consistently decreases both particle size and mass. The strong agreement between CHAPS measurements and CK-EDB data suggests that aerosol plume behaviour can be accurately modelled from single droplet data.</p><p><strong>Conclusion: </strong>The study highlights ethanol's role in optimizing particle size distribution, which is crucial for enhancing the therapeutic efficiency of inhaled medications. These results underscore the importance of tailoring formulation and environmental conditions to improve drug delivery outcomes in pulmonary therapies and the importance of recognising that aerosol particle size distributions are dynamic and highly compositionally dependent.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"651-663"},"PeriodicalIF":3.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764615","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}

{"title":"A Preformulation Experiment: The Influence of Poloxamer 188 and Poloxamer 407 on the Binding Coefficients (Single Molecule) and the Partitioning Coefficients (Micelle) of Ketoprofen (Probe Molecule) with Sodium Cholate, Dodecyl Trimethylammonium Bromide and BrijC10 Surfactants.","authors":"Zita Farkaš Agatić, Vesna Tepavčević, Mladena Lalić-Popović, Nemanja Todorović, Ana Stjepanović, Mihalj Poša","doi":"10.1007/s11095-025-03852-0","DOIUrl":"10.1007/s11095-025-03852-0","url":null,"abstract":"<p><strong>Introduction: </strong>Ketoprofen, a Biopharmaceutics Classification System (BCS) class II drug, exhibits poor water solubility, necessitating solubilization strategies for effective drug delivery. Surfactants and poloxamers are commonly employed to enhance solubilization via micellar encapsulation and host-guest interactions.</p><p><strong>Aim: </strong>This study investigates the binding interactions, stoichiometry, and partitioning behavior of ketoprofen with surfactants-sodium cholate (SC), dodecyltrimethylammonium bromide (DTAB), and Brij C10 (BC10)-and examines the impact of Poloxamer 188 (P188) and Poloxamer 407 (P407) as modifiers.</p><p><strong>Materials and methods: </strong>Complexation stoichiometry was evaluated using Job's plots, while binding constants (K_b​) were derived from Benesi-Hildebrand plots. Partition coefficients (K_x) and Gibbs energies (ΔG_x​) were determined using Kawamura's equation. Measurements were conducted at 25°C with constant ketoprofen concentrations.</p><p><strong>Results and discussion: </strong>Job's plots indicated 1:1 complexation for most systems, except DTAB + P407, which exhibited a 1.67:1 ratio. DTAB displayed the highest K_x (81386.259 with P188), attributed to electrostatic interactions and micelle stabilization. SC showed moderate K_x​, reduced by poloxamers due to competitive hydrogen bonding. BC10, the least efficient solubilizer, improved slightly with poloxamers by enabling micellar core partitioning. Gibbs energy (ΔG_x < 0) confirmed spontaneous solubilization, with the most favorable values for DTAB + P188. Discrepancies between Job's and Benesi-Hildebrand plots highlighted the limitations of the latter for low-CMC surfactants.</p><p><strong>Conclusion: </strong>DTAB, particularly with P188, demonstrated the greatest potential for ketoprofen solubilization, providing valuable insights for designing surfactant-based drug delivery systems.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"711-724"},"PeriodicalIF":3.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788756","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":"Population Pharmacokinetics of IV Lidocaine and its Metabolites in Adult Surgical Patients.","authors":"Keng Wah Foong, Pui San Loh, Sook Hui Chaw, Yoke Lin Lo","doi":"10.1007/s11095-025-03835-1","DOIUrl":"10.1007/s11095-025-03835-1","url":null,"abstract":"<p><strong>Background: </strong>Perioperative lidocaine infusions show potential as a systemic analgesic and to enhance postoperative recovery. This study characterised the pharmacokinetics (PK) of lidocaine and its metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), in adult surgical patients using non-linear mixed-effects modelling.</p><p><strong>Methods: </strong>Thirty-four donor nephrectomy and 64 cholecystectomy patients received intraoperative IV lidocaine. Plasma samples were collected perioperatively and analysed in NONMEM. Covariate effects and alternative dosing regimens were investigated.</p><p><strong>Results: </strong>1,520 concentration-timepoints were analysed. Lidocaine PK was best fitted with a 3-compartment model, while MEGX and GX used a 2-compartment model. All parameters were scaled allometrically with total body mass and fat-free mass (FFM). Lidocaine had a typical clearance of 45.9 L/h, decreasing by 60% postoperatively, and a central volume of 25.2 L. Peripheral compartments 1 and 2 exhibited intercompartmental clearances of 142 L/h and 5.81 L/h, with volumes of 44.4 L and 29.3 L, respectively. Peripheral compartment 1's volume expanded with intraoperative fluid administration. Simulations suggested an FFM-based dosing regimen (bolus: 2.5 mg/kg over 30 min, single infusion: 2 mg/kg over 1 h, maintenance infusion: 1.5 mg/kg/h) quickly achieved and maintained a lidocaine target plasma concentration of 1.5 mg/L.</p><p><strong>Conclusions: </strong>The joint parent-metabolites model adequately describes the disposition of lidocaine and its metabolites, incorporating allometric scaling and key covariates. It provides a foundation for optimising lidocaine dosing and guiding investigations to establish target plasma concentrations for safe and effective use in the general surgical population. Further research is warranted to refine and evaluate the model's utility in other surgical populations.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"451-473"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531751","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":"Phytochemicals and their Nanoformulations for Overcoming Drug Resistance in Head and Neck Squamous Cell Carcinoma.","authors":"Zhai Pingping, Chen Nan, Tang Yong","doi":"10.1007/s11095-025-03836-0","DOIUrl":"10.1007/s11095-025-03836-0","url":null,"abstract":"<p><strong>Background: </strong>Drug resistance remains a significant challenge in the treatment of head and neck squamous cell carcinoma (HNSCC), leading to therapeutic failure and poor patient prognosis. Numerous mechanisms, including drug efflux pumps, altered tumor microenvironment (TME), and dysregulated cell death pathways, contribute to the development of resistance against conventional chemotherapeutic agents, immunotherapy, and targeted therapies. As resistance to traditional treatments continues to emerge, there is an urgent need for innovative therapeutic strategies to overcome these challenges. Phytochemicals are naturally occurring bioactive compounds and have demonstrated remarkable potential in targeting multiple resistance mechanisms simultaneously.</p><p><strong>Method: </strong>This review comprehensively overviews the current understanding of drug resistance mechanisms in HNSCC and explores innovative strategies utilizing phytochemicals and their nanoformulations to overcome these resistance mechanisms, with a particular focus on recent developments and future perspectives in this field.</p><p><strong>Results and discussion: </strong>Phytochemicals with anticancer properties include a wide range of herbal-derived molecules such as flavonoids, stilbenes, curcuminoids, alkaloids, traditional Chinese medicine, and others. These compounds can modulate ATP-binding cassette transporters, reverse epithelial-to-mesenchymal transition (EMT), target cancer stem cells (CSCs), and regulate various signaling pathways involved in drug resistance. The integration of phytochemicals into advanced nanoformulation systems has also shown a remarkable improvement in enhancing their bioavailability, stability, and targeted delivery to the TME, potentially improving their therapeutic efficacy. Furthermore, the combination of phytochemicals with conventional chemotherapeutic agents, targeted molecular therapy, and immune checkpoint inhibitors (ICIs) has exhibited synergistic effects, offering a promising approach to restoring drug sensitivity in resistant HNSCC cells.</p><p><strong>Conclusion: </strong>Phytochemicals and their nanoformulations may improve response of HNSCC to therapy by alleviating drug resistance.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"429-449"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542977","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":"Development of a Melting Point Depression Method to Measure the Solubility of a Small-Molecule Drug in Poly-Lactic-co-Glycolic Acid (PLGA).","authors":"Coleman Johnson, Feng Zhang","doi":"10.1007/s11095-025-03840-4","DOIUrl":"10.1007/s11095-025-03840-4","url":null,"abstract":"<p><strong>Purpose: </strong>The solubility of a crystalline drug in a polymer is commonly determined by measuring melting point depression with differential scanning calorimetry (DSC). The accuracy of this measurement depends on rapid dissolution of the drug into the molten polymer during the DSC heating scan. A preferred method of accelerating this dissolution process is to preblend the drug and polymer by cryo-milling. However, cryo-milling may be unsuitable for water-sensitive drugs or polymers such as poly(lactic-co-glycolic acid) (PLGA). The purpose of this study was to develop a PLGA-specific melting point depression method that did not require a cryo-milling operation.</p><p><strong>Methods: </strong>A three-step DSC method was used to measure the solubility of a small-molecule drug, voriconazole, in amorphous PLGA (Resomer ® RG 502H). First, drug/PLGA powder mixtures of multiple drug loadings were melted and rapidly cooled to form glassy solid solutions. Second, these solid solutions were heated above their T_g until the drug crystallized. Third, these crystallized samples were slowly heated to measure melting point depression (i.e., solubility temperatures).</p><p><strong>Results: </strong>The crystallization procedure generated the desired drug polymorph and likely generated small, well-mixed crystalline drug particles, as the drug dissolved rapidly into the molten polymer during melting point depression scans. Drug/PLGA solubility temperatures were determined with confidence between 40 - 100% drug loading. The solubility curve was extrapolated to lower drug loadings using the Flory-Huggins model.</p><p><strong>Conclusion: </strong>This technique can assist product development of high-drug-loaded PLGA products, particularly those manufactured by melt extrusion.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"529-543"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573147","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":"Editorial Expression of Concern: Nano-Targeted Delivery of Toremifene, an Estrogen Receptor-α Blocker in Prostate Cancer.","authors":"Waseem Hariri, Thangirala Sudha, Dhruba J Bharali, Huadong Cui, Shaker A Mousa","doi":"10.1007/s11095-025-03847-x","DOIUrl":"10.1007/s11095-025-03847-x","url":null,"abstract":"","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"545"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634454","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":"In Vitro-In Vivo Correlation Of Amorphous Solid Dispersion Enabled Itraconazole Tablets.","authors":"Ana L Coutinho, Asmita Adhikari, Samuel Krug, Maureen Kane, R Gary Hollenbeck, Stephen W Hoag, James E Polli","doi":"10.1007/s11095-025-03837-z","DOIUrl":"10.1007/s11095-025-03837-z","url":null,"abstract":"<p><strong>Purpose: </strong>There are scarce reports on in vitro-in vivo correlation (IVIVC) model development of immediate-release (IR) formulations, and few investigations of the impacts of formulation and process of spray-dried solid dispersions (SDD)-based tablets on human pharmacokinetics (PK), despite commercial product successes. The goal of this study was to investigate the formulation and process factors that impact bioavailability enhancement of IR itraconazole SDD tablets; and to develop an FDA level A IVIVC that would predict in vivo PK performance from in vitro dissolution testing.</p><p><strong>Methods: </strong>A direct, differential-equation-based IVIVC model approach was employed, using an oral solution for post-dissolution disposition and Fast-, Medium-, and Slow-release tablets.</p><p><strong>Results: </strong>The IVIVC met FDA internal predictability for level A IVIVC requirements. The in vitro dissolution employed USP simulated intestinal fluid (phosphate buffer), adjusted pH 6.4, and tablets were triturated into particles prior to their immersion into dissolution media to mimic the attenuated disintegration difference between Medium and Slow in vivo. Credibility assessment of the FDA level A IVIVC model was performed, including model verification and validation considerations in light of the question of interest, the context of use, and model risk.</p><p><strong>Conclusion: </strong>To our knowledge, this is the first and only study that successfully developed an FDA level A IVIVC of an amorphous solid dispersion, which assessed the impact of grades of the same polymer, disintegrant level, and dry granulation processing on the performance of SDD tablets in humans.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"485-502"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606028","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}