AAPS PharmSciTech最新文献

{"title":"High-Contrast X-Ray Computed Tomography for Quantifying Amorphous Content in Melt-Quenched Acetaminophen","authors":"Tamaki Miyazaki,&nbsp;Yoshihiro Takeda,&nbsp;Kazuki Ito,&nbsp;Kazuki Omoto,&nbsp;Daisuke Ando,&nbsp;Tatsuo Koide,&nbsp;Yoji Sato","doi":"10.1208/s12249-026-03372-z","DOIUrl":"10.1208/s12249-026-03372-z","url":null,"abstract":"<div><p>X-ray computed tomography (XRCT) allows for non-destructive three-dimensional observation and volumetric quantification of samples. It also allows for structural changes monitoring, such as the amorphous-to-crystalline transition in pharmaceuticals, over time. Despite past applications of XRCT to characterize amorphous pharmaceuticals, its quantitative validity has not been systematically verified against established thermal methods. Here, we evaluated laboratory XRCT for monitoring the crystallization behavior of amorphous acetaminophen and validated its accuracy via differential scanning calorimetry (DSC). In XRCT, amorphous content was determined from voxel-based phase segmentation, while DSC estimates were obtained from the specific heat change at the glass transition temperature. Time-dependent crystallization at 30°C was quantified using XRCT followed immediately by DSC, showing strong correlation (R² = 0.990). These results demonstrated that XRCT provides a reliable, voxel-based measure of amorphous fraction, despite the limited precision imposed by the micrometer-scale spatial resolution. XRCT enables continuous monitoring of a single sample—from preparation through near-complete crystallization—and reduces the number of samples required to construct crystallization profiles. <i>In situ</i> XRCT enabled visualization of the initial sites of detectable crystallization and its spatial propagation within the sample, revealing information unattainable from bulk thermal analysis. Herein, phase-retrieval image processing improved phase discrimination, although the processing effect could be influenced by sample type or experimental conditions. The XRCT method is proposed not for precise quantification, but as a practical and efficient tool for rapid screening of physical stability, formulation development, and assessment of storage conditions in early-stage pharmaceutical development.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146218142","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":"Physicochemical Characterization and In Vitro Evaluation of Novel Liposomal and Proliposomal Doxorubicin Formulations in Accordance with FDA Guidance","authors":"Gülbeyaz Yıldız Türkyılmaz,&nbsp;Mine Diril,&nbsp;H. Yeşim Karasulu","doi":"10.1208/s12249-026-03357-y","DOIUrl":"10.1208/s12249-026-03357-y","url":null,"abstract":"<div><p>Doxorubicin (Dox) is a widely used chemotherapeutic agent, but its clinical application is limited by severe dose-dependent toxicities, particularly cardiotoxicity. To overcome these challenges, two novel formulations—liposomal doxorubicin (Dox-Lip) and proliposomal doxorubicin (Dox-P-Lip) —were developed and systematically compared with the reference listed drug (RLD), focusing on physicochemical comparability and <i>in vitro</i> bioequivalence in accordance with FDA guidance. Dox-Lip was prepared using alternative lipid compositions and a modified pH gradient–based active loading method, while Dox-P-Lip was obtained by lyophilization of the liposomal formulation. Characterization studies included encapsulation efficiency (EE%), lipid content, drug-to-lipid ratio, internal pH, morphology, bilayer phase behavior, PEG surface density, particle size, zeta potential, and PEG layer thickness determined using the Fixed Aqueous Layer Thickness (FALT) model. <i>In vitro</i> drug release was evaluated under simulated plasma, variable pH and temperature, and ultrasound exposure. Both formulations exhibited high encapsulation efficiencies (EE%) exceeding 90%, comparable to those of the RLD. Moreover, these formulations demonstrated approximately 2.1-fold thicker PEG layers, indicating improved steric stabilization. Although these formulations exhibited slightly higher leakage under stress conditions, the encapsulation efficiency (EE%) consistently remained above 90%, confirming their structural integrity. Overall, the novel formulations demonstrated physicochemical similarity and stability relative to the RLD, supporting their potential as bioequivalent and clinically viable liposomal Dox alternatives.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 2","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-026-03357-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146163453","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":"In Vitro Permeation Testing of Sunscreens using Reconstructed Human Skin versus Human Cadaver Skin Models","authors":"Kartik R. Roy,&nbsp;Apipa Wanasathop,&nbsp;Lijing Xu,&nbsp;Jiang Wang,&nbsp;Sergio G. Coelho,&nbsp;Steven A. Adah,&nbsp;Theresa M. Michele,&nbsp;Patrick J. Faustino,&nbsp;Muhammad Ashraf,&nbsp;Xiaoming Xu,&nbsp;Yang Yang","doi":"10.1208/s12249-026-03343-4","DOIUrl":"10.1208/s12249-026-03343-4","url":null,"abstract":"<div><p><i>In vitro</i> permeation testing (IVPT) is a method widely used to assess the skin permeation profiles of topical drug products for product development and regulatory evaluation. Various skin models serve as diffusion barriers in IVPT, including surgically excised human skin (EHS) and human cadaver skin (HCS). Limited EHS supply has led to the use of HCS in IVPT, but HCS shows variable skin permeation among donors, creating challenges in obtaining consistent results. To address these supply and variability issues, this study evaluated the potential of reconstructed human skin (RHS) as an alternative diffusion barrier for IVPT. Sunscreen (cream) permeation through four skin models were compared, including two HCS models and two RHS models with or without dermal layers. Among the tested skin models, EpiDermFT (RHS with dermal layers) exhibited consistent results for both intra-batch and inter-batch permeation. Additionally, EpiDermFT exhibited similar rank order of cumulative permeation compared to the HCS counterpart, whereas EpiDerm (RHS without dermal layers) exhibited greater sensitivity to pH changes in cream formulations than HCS models. These findings suggest that EpiDermFT has potential utility as a reliable alternative that provides comparable permeation results to HCS, whereas EpiDerm may serve as a sensitive tool to detect pH differences in topical formulations. However, to determine the broader applicability of RHS in IVPT, further investigations using diverse topical formulations across different dosage forms are necessary.\u0000</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 2","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146155705","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":"Analysis of the Correlation Between Membrane Permeability in RPMI 2650 Cells and Human Nasal Absorption","authors":"Tokio Morita,&nbsp;Toshiaki Tsuchitani,&nbsp;Hiroyuki Yoshida,&nbsp;Naomi Tomita,&nbsp;Yoji Sato","doi":"10.1208/s12249-026-03331-8","DOIUrl":"10.1208/s12249-026-03331-8","url":null,"abstract":"<div><p>Nasal drug delivery offers several advantages, such as rapid onset and avoidance of hepatic first-pass metabolism, making it a promising option for delivering drugs both locally and systemically. In the early phases of pharmaceutical development, predictive tools for nasal absorption are critical for selecting suitable candidates. This study evaluates the utility of RPMI 2650 cells as an <i>in vitro</i> model for predicting nasal drug absorption. First, we confirmed the reproducibility of membrane permeability across two air–liquid interface culture conditions (shifted on days 1 and 3), demonstrating consistent permeability profiles and agreement with previously reported <i>P</i>_app values. We investigated the correlation between the permeability of RPMI 2650 cells and both clinical nasal bioavailability (nasal BA) and the estimated human nasal fraction absorbed (nasal Fa), revealing good correlations in both cases. To our knowledge, this is the first study to demonstrate a significant correlation between <i>in vitro</i> permeability and estimated human nasal Fa levels. Although some compounds deviated from the correlation curve, these findings indicate that RPMI 2650 cells are useful <i>in vitro</i> tools for predicting nasal drug absorption during the early phases of pharmaceutical development.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 2","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146155690","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":"Quality by Design Integration of Design of Experiments for Tablet Formulation Optimization and Process Validation","authors":"Jirapornchai Suksaeree,&nbsp;Chaowalit Monton,&nbsp;Pattwat Maneewattanapinyo","doi":"10.1208/s12249-026-03335-4","DOIUrl":"10.1208/s12249-026-03335-4","url":null,"abstract":"<div><p>Quality by design (QbD) and design of experiments (DoE) have become central to modern pharmaceutical development, yet most guidance and reviews treat formulation development, process optimization, and process validation as largely separate activities. This narrative review focuses specifically on oral tablet products and traces how formulation-level DoE can be used to systematically define, refine, and confirm design space across the full lifecycle of tablet development. Published case studies are organized along a formulation-to-validation pathway, beginning with the translation of the target product profile (TPP) into tablet-specific quality TPPs and critical quality attributes, followed by risk assessment and the selection of appropriate screening, mixture, and response-surface designs for both formulation and process studies. Subsequent sections highlight how DoE outputs support probabilistic and mechanistic design space definition, scale-up and technology transfer, and the alignment of Stage 1–3 process validation activities with QbD principles. Particular attention is given to challenges in integrating DoE with process analytical technology (PAT), model lifecycle management, and data-driven control strategies. This review synthesizes these elements into a practical framework for tablet scientists and manufacturing teams. We outline ways to embed DoE into QbD-based development for tablets and highlight key gaps, including the limited use of probability-based design spaces and digitally enabled validation.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 2","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146155714","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":"Recent Trends in the Development and Clinical Translation of Polymer-based Targeted Therapeutic Nanoparticle","authors":"Chandan Kumar Singh,&nbsp;Ratnali Bania,&nbsp;Satyendra Deka,&nbsp;Monika Dwivedi,&nbsp;Anroop B. Nair,&nbsp;Trishna Bal,&nbsp;Prasenjit Maity,&nbsp;Pran Kishore Deb","doi":"10.1208/s12249-025-03319-w","DOIUrl":"10.1208/s12249-025-03319-w","url":null,"abstract":"<div><p>Polymeric nanoparticles are a state-of-the-art innovation in nanomedicine, offering site-specific drug delivery, an improved pharmacokinetic profile, and a reduced systemic toxic profile. These nano systems usually range in size between 10 to 100 nm, and have the ability to trap a wide range of pharmacological agents, releasing them on a timed basis to specific sites related to the disease, which improves clinical outcomes. Other novel applications of nanoparticles have included polymer-metal theranostic nanoparticles, which combine both diagnostic and therapeutic functions into a single platform. Further development of the polymeric nanocarrier to clinical application is however complex because of the complex design variables, lack of batch-to-batch properties, scale effects, as well as regulatory uncertainty, due to the fact that the formulation and optimisation of nanoparticles is a long-term and intricate process, scientists actively use artificial intelligence (AI) and machine learning (ML) to learn more about the pattern of drug release in nanoparticles, optimisation of AI and ML is also being done. These barriers are being overcome more and more by using artificial intelligence (AI) and machine learning (ML) to design and optimise nanoformulations. These tools facilitate the forecasting of nanoparticles' behaviour, speed up formulation development, and optimise the pre-clinical and clinical workflow. The success rate of regulatory approvals of polymeric drug delivery systems is, however, modest despite encouraging pre-clinical outcomes. The downfall of the projects is usually linked to inadequate physicochemical characterisation, safety issues and vague regulatory pathways. However, some formulations have managed to overcome these challenges, albeit with the need for a robust design plan, thorough pre-clinical testing, and initial interaction with regulatory authorities. This review explores the rationale behind the development of polymeric nanoparticles, recent AI-driven advancements, and the unique dual-functional capabilities of polymer–metal theranostics. It also examines the factors influencing success or failure in clinical and regulatory settings. Collectively, these insights emphasise the transformative promise of polymeric nanomedicine and highlight the urgent need for integrated technological and regulatory approaches to expedite clinical translation.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 2","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117521","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":"Delivery Strategies and Clinical Significance of Oral Colon-targeted Drug Delivery Systems","authors":"Kailash Bansal,&nbsp;Amit Mukharya,&nbsp;Anil B. Jindal","doi":"10.1208/s12249-026-03348-z","DOIUrl":"10.1208/s12249-026-03348-z","url":null,"abstract":"<div><p>Formulation strategies for colonic delivery offer a unique opportunity for the local delivery of drugs for symptomatic relief in inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and colorectal cancer, as well as for the systemic delivery of peptides and biologics. By releasing active pharmaceutical ingredients (APIs) directly at the site of action within the colon, these systems can achieve higher local exposure with reduced systemic effects. This is achieved by utilizing prodrugs, pH-sensitive polymers, time-dependent systems, pressure, microbiota, and multi-pronged systems. Monolithic delivery systems can deliver drugs to the colon with limitations; however, the multiparticulate drug delivery of pellets has proven to be a superior methodology in meeting targets. This review highlights various techniques to bypass the upper part of the gastrointestinal tract, thereby releasing the active pharmaceutical ingredient specifically in various parts of the intestine and colon, to achieve both local and systemic therapeutic effects.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 2","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146083132","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":"AI-enabled, QbD-aligned Predictive, and Sustainable Design of Natural Polymer-based Drug Delivery Systems","authors":"Jirapornchai Suksaeree,&nbsp;Pattwat Maneewattanapinyo,&nbsp;Chaowalit Monton","doi":"10.1208/s12249-026-03326-5","DOIUrl":"10.1208/s12249-026-03326-5","url":null,"abstract":"<div><p>Natural polymers such as chitosan, alginate, cellulose, gelatin, and silk fibroin have become central to modern drug delivery research due to their biocompatibility, biodegradability, and environmental sustainability. However, variability in source, molecular weight, and crosslinking chemistry often results in inconsistent formulation performance and limited scalability. To overcome these challenges, artificial intelligence (AI) and machine learning frameworks have been increasingly integrated into formulation science under the quality by design paradigm. This review synthesizes current advances in AI-assisted modeling and optimization of natural polymer drug delivery systems, highlighting how predictive algorithms capture nonlinear relationships among polymer structure, process variables, and release kinetics. Neural-network and Bayesian-optimization models demonstrate accurate prediction of encapsulation efficiency and dissolution profiles, while hybrid mechanistic–AI and physics-informed neural networks enhance interpretability by embedding kinetic and diffusion equations. The review also discusses data-generation workflows, FAIR-compliant standards, and polymer-informatics databases that enable interoperable, reproducible modeling. Collectively, these developments establish a pathway toward data-driven, sustainable pharmaceutics, where predictive and eco-designed formulations replace empirical trial-and-error methods. Remaining challenges include dataset standardization, model transparency, and regulatory validation. Addressing these will accelerate the translation of intelligent polymer design into reproducible, scalable, and environmentally responsible drug delivery innovations.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 2","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146082770","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":"Process Optimisation, Pharmaceutical Characterisation, and in vitro Activity of Mesalamine Nanocrystals in PMA-differentiated THP-1 cell Lines in the Late Inflammatory and Profibrotic Phase","authors":"Sonam Sharma,&nbsp;Sakshi Kunjir,&nbsp;Sadhana Dhyagala,&nbsp;Abhishek Sahu,&nbsp;Subramanian Natesan,&nbsp;Rajkumar Malayandi","doi":"10.1208/s12249-026-03333-6","DOIUrl":"10.1208/s12249-026-03333-6","url":null,"abstract":"<div><p>Mesalamine (MES) remains a first-line therapy for the treatment of inflammatory bowel disease; however, its clinical use is limited by poor aqueous solubility in the colon, high dose requirements, variable pharmacokinetics, pill burden, and patient non-compliance. This study aimed to develop and optimise MES nanocrystals (MES NCs) using a top-down ball milling approach using a stabiliser Hydroxypropyl methylcellulose acetate succinate (HPMC-AS). Thirteen different batches were formulated to assess the effects of speed and time of milling, and polymer concentration on particle size, polydispersity index (PDI), morphology, crystallinity, thermal properties, and dissolution. The B11 batch was evaluated for its biological activity using PMA-differentiated THP 1 cell line treated with LPS using inflammatory markers: IL-4, IL-6, TNFα, and TGF-β. The first reproducibility batches (0.1/400/40; B9-B15) exhibited an intra-batch average particle size of 537.3 ± 139.2 nm with a PDI of 0.5 ± 0.1. SEM analysis confirmed a uniform plate-like morphology. PXRD analysis revealed partial peak shifts and broadening, suggesting lattice strain in the milled NCs. Dissolution studies demonstrated pH-dependent release of MES-NCs. FTIR confirmed drug-polymer compatibility. Cytotoxicity testing in PMA-differentiated THP-1 macrophage-like cells showed &gt; 64% cell viability at therapeutic MES NC concentrations up to 2.5 µM. Type 2 cytokines (IL-4), typically induced by LPS in the late phase, showed a time-dependent response, further supporting the immunomodulatory effect of MES NCs. The B11 batch significantly increased TGF-β expression compared with the disease group, suggesting activation of regulatory anti-inflammatory pathways with M2 macrophage polarisation.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 2","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146082750","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":"Nanocrystallization and Microencapsulation of Natural Pigments for Improved Dissolution and Stability","authors":"Zhitao Cai,&nbsp;Hanyan Gong,&nbsp;Sishu Li,&nbsp;Yu Zhang,&nbsp;Tian Yin,&nbsp;Haibing He,&nbsp;Jingxin Gou,&nbsp;Yanjiao Wang,&nbsp;Xing Tang","doi":"10.1208/s12249-026-03325-6","DOIUrl":"10.1208/s12249-026-03325-6","url":null,"abstract":"<div><p>Natural lipophilic pigments typically exhibit poor water solubility, low dissolution rates, and photothermal instability, which hinder their pharmaceutical application. To address these challenges, a nanosuspension–microencapsulation delivery system was developed using curcumin (CUR) and lutein (LUT) as model compounds to enhance dissolution and stability. Hydroxypropyl methylcellulose E5 (HPMC-E5) was identified as the optimal stabilizer for CUR and LUT nanosuspensions (NS) prepared by antisolvent precipitation and optimized by wet media milling. The resulting CUR-NS achieved a rapid dissolution of 93.29 ± 3.43% within 5 min compared with 26.71 ± 1.11% for raw CUR, while LUT-NS reached 85.13 ± 2.27% at 120 min <i>versus</i> 13.35 ± 1.32% for raw LUT. To enhance powder properties and stability, nanosuspensions were transformed into microcapsules via spray drying and bottom-spray fluidized bed coating, yielding drug loadings of 10–30%. The spray-dried CUR microcapsules exhibited poor flowability (angle of repose: 47°), which improved to 33° after surface modification with 3% colloidal silica. In contrast, CUR and LUT microcapsules prepared with sucrose-based cores via fluidized bed coating showed larger particle sizes, smoother surfaces, excellent flowability (angle of repose ~ 20°), and direct compression suitability. Accelerated stability tests revealed 1.3- to fourfold improvements in resistance to heat, light, and humidity compared with the raw pigments. Furthermore, compressibility evaluations confirmed good tableting performance for all microcapsules. Overall, this study demonstrates a robust nanosuspension–microencapsulation strategy that markedly enhances the dissolution, stability, and processing performance of poorly soluble natural pigments, highlighting its promise for industrial formulation and application.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 2","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146082749","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}