AAPS PharmSciTech最新文献

{"title":"Bergapten-Loaded Dissolving Microneedles for Vitiligo Treatment: A Synergistic Strategy Combining Nanocrystal Technology and Physical Enhancement","authors":"Lingzhi Lu,&nbsp;Huifen Yang,&nbsp;Ruda Liu,&nbsp;Chunxue Li,&nbsp;Yuzhu Yang,&nbsp;Rongping Yang,&nbsp;Yuanfang Hou","doi":"10.1208/s12249-026-03509-0","DOIUrl":"10.1208/s12249-026-03509-0","url":null,"abstract":"<div><p>Bergapten can effectively treat vitiligo by increasing the activity of melanocytes and tyrosinase, but its low solubility and poor transdermal effect limit its application. In this study, we used dissolvable microneedles (shells) loaded with bergapten nanocrystals (cores), a shell-nucleus-type formulation design, to treat vitiligo, organically integrating physical and pharmacological treatments, and to improve drug delivery efficiency. Firstly, bergapten was prepared into nanocrystals and screened for dissolvable microneedle matrix, and dissolvable microneedles were prepared by centrifugal spin-coating method; then, the quality studies of bergapten nanocrystals dissolvable microneedles (BP-NCs-DMNs) were carried out on the mechanical properties, <i>in vitro</i> solubility properties, skin puncture, and skin barrier restorative measurements and transdermal cumulative permeation experiments; finally, the pharmacological effects of bergapten dissolvable microneedles against vitiligo were verified by determining the tyrosinase (TYR), Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), and superoxide dismutase (SOD) levels using a hydroquinone-induced mouse vitiligo model. As a result, the prepared bergapten microneedles could penetrate into the skin, and the skin did not show any redness, swelling, or excessive inflammation after removing the microneedles, and they could be dissolved <i>in vitro</i> in about 35 min. As a result of the <i>in vitro</i> transdermal experiment, the cumulative transmittance of bergapten in 24 h of bergapten microneedle was 257.9 μg/cm², and the skin absorption rate of the drug was (57.15 ± 2.61) %. The hydroquinone-induced vitiligo model in mice further verified the effect of bergapten micropigmentation on skin pigmentation in mice. In this study, dissolvable bergapten microneedles were successfully established, which can significantly improve the transdermal drug delivery efficiency of bergapten and can effectively treat vitiligo disease.</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 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148927835","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":"Spray Freeze Drying for Solid Formulations of RNA Lipid Nanoparticles","authors":"Kinnari Santosh Arte,&nbsp;Rachana Sapkota,&nbsp;Chanakya D. Patil,&nbsp;Yijing Huang,&nbsp;Eric J. Munson,&nbsp;Sajal Patel,&nbsp;Nicole Payton,&nbsp;Rushit Lodaya,&nbsp;Qi (Tony) Zhou,&nbsp;Li (Lily) Qu","doi":"10.1208/s12249-026-03516-1","DOIUrl":"10.1208/s12249-026-03516-1","url":null,"abstract":"<div><p>Spray-freeze drying (SFD) is a promising drying technique for stabilizing RNA lipid nanoparticles (RNA-LNPs) by converting them into solid-state formulations. This study examined the impact of the SFD process and the widely utilized stabilizing disaccharides, such as sucrose and trehalose, on the major properties (e.g. particle size, encapsulation efficiency) of RNA-LNPs post drying. Various process parameters, such as atomization, freezing, and drying temperature, were systematically evaluated, along with the impact of incorporating annealing post freezing step. Surface area measurements, solid-state particle size analysis, scanning electron microscopy, powder X-ray diffraction and solid-state NMR spectroscopy were employed to gain deeper insights into powder characteristics and matrix mobility. Our findings demonstrated that sucrose provided superior stabilization as compared to trehalose in our tested formulations and processes. Moreover, incorporation of the annealing process enhanced LNP stability. Results from the stability study revealed that the annealed 10% and 20% sucrose formulations maintained their stability, highlighting the potential of optimized SFD processing for producing solid formulations of RNA-LNPs.</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 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-026-03516-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918071","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":"Nanosuspension-based Ocular Therapeutics for Infection Control: Integrating Mucin Interactions and Tear Film Dynamics","authors":"Deepanjan Datta,&nbsp;Maria Nison,&nbsp;Viola Colaco,&nbsp;Vandana Krishna,&nbsp;Sony Priyanka Bandi,&nbsp;Namdev Dhas,&nbsp;Swati Biswas,&nbsp;Riya Singh,&nbsp;Vasudev R Pai","doi":"10.1208/s12249-026-03531-2","DOIUrl":"10.1208/s12249-026-03531-2","url":null,"abstract":"<div><p>Ocular infections can affect the ocular surface and adnexal structures, intraocular structures, or both. Infections of the ocular surface and adnexa often arise from the invasion of commensals when typical barriers are compromised, which includes infectious blepharitis, conjunctivitis, keratitis, dacryocystitis, and orbital infections, among others. Intraocular infections may develop due to localised trauma or as part of a systemic condition. A variety of viruses, bacteria, fungi, protozoa, and helminths can cause intraocular illness. Occasionally, ocular abnormalities are the only external clinical indications of systemic infectious diseases. Analyzing specimens from ocular tissues or fluids can aid in diagnosing ocular infectious diseases and may help identify systemic infections. The management of ocular illnesses generally involves the topical application of antimicrobials and anti-inflammatory agents, along with targeted therapy addressing the underlying etiologies. In some cases, systemic antibacterial agents or glucocorticoids may be necessary. Addressing an inflamed or infected eye in an emergency context poses a diagnostic and therapeutic challenge for the emergency physician, with aetiology and prognoses varying from benign, self-limiting conditions to organ-threatening diseases. To address these ocular infections, the market has evolved with various therapeutics-based eye drops that are instilled specifically into the lower precorneal pocket and are regarded as the most patient-compliant method of drug delivery. Nevertheless, the efficacy of this approach is significantly reduced by the blink reflex, resulting in the loss of most of the topical dose. In this regard, nanosuspensions, which disperse hydrophobic drugs in an aqueous medium stabilised by surfactants, offer a promising strategy for mitigating ocular infections. Overall, this review aims to thoroughly examine the applicability of nanosuspensions in ocular drug delivery to target and treat infections in the human eye.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-026-03531-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918044","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":"Direct Powder Extrusion of Atorvastatin 3D-Printed Tablets for Immediate-Release: Solid-State Characterization and Dissolution Performance","authors":"Thirupathi Reddy Anekalla,&nbsp;Sujith Raj Bashetty,&nbsp;Navya Nalajala,&nbsp;Nagarjuna Narala,&nbsp;Tejaswi Appidi,&nbsp;LR Jaidev Chakka,&nbsp;Mohammed Maniruzzaman","doi":"10.1208/s12249-026-03507-2","DOIUrl":"10.1208/s12249-026-03507-2","url":null,"abstract":"<div><p>Thermal extrusion is a well-established approach for producing amorphous solid dispersions (ASDs) to enhance the solubility, dissolution, and bioavailability of poorly water-soluble drugs. Atorvastatin calcium trihydrate (ACT), a BCS class II lipid-lowering agent, exhibits low aqueous solubility, limited oral bioavailability, and variable absorption. The present study investigated the feasibility of fabricating immediate-release ACT tablets using a direct powder extrusion (DPE) three-dimensional (3D) printing technique, thereby enabling in situ drug amorphization and tablet fabrication in a single step. Critical process parameters (CPPs), including nozzle speed, printhead temperature, infill density, and extrusion pressure, were systematically optimized to achieve reproducible oval-shaped tablets with acceptable mechanical integrity and structural fidelity. Among the evaluated polymeric systems for improved dissolution, a combination of 25% (w/w) polyethylene glycol (PEG), 25% (w/w) polyethylene oxide (PEO), 15% (w/w) Pluronic F127, and 15% (w/w) sorbitol yielded consistent DPE printing at a 25% infill density, which has been shown to improve dissolution. The 3D-printed tablets, characterized by physicochemical, structural, and thermal analyses, confirmed successful drug amorphization. <i>In vitro</i> dissolution testing in phosphate buffer (PBS, pH 6.8) demonstrated rapid tablet disintegration and immediate drug release, with ~86% of ACT released within 30 min, meeting United States Pharmacopeia (USP) specifications for immediate-release ACT tablets. Accelerated stability studies (40°C/75% RH) for 3 months showed retention of the amorphous state, as confirmed from DSC and pXRD, with dissolution profiles comparable to initial results. Overall, the findings demonstrated that DPE-based thermal extrusion 3D printing enables single-step fabrication of amorphous ACT tablets with improved dissolution performance and stability, highlighting its potential as a single-step, flexible, patient-centric manufacturing platform at the point of service.</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 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-026-03507-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148917935","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":"Real-Time Monitoring of Tablet API Concentration and Bioavailability via Dissolution Kinetics in Simulated Stomach Fluid by T-Ray Transmission Technique","authors":"Anis Rahman,&nbsp;Rafiq Islam,&nbsp;Bozena Michniak-Kohn","doi":"10.1208/s12249-026-03515-2","DOIUrl":"10.1208/s12249-026-03515-2","url":null,"abstract":"<div><p>This paper introduces a real-time, separationless method for monitoring Active Pharmaceutical Ingredient (API) concentration and dissolution kinetics in oral tablets using terahertz radiation (T-ray) transmission kinetics within simulated stomach fluid. Unlike conventional techniques such as High-Performance Liquid Chromatography (HPLC), which produce only discrete data points and require labor-intensive sample preparation, the T-ray approach offers continuous, quantitative measurement and monitoring. By leveraging the unique transmission and absorption characteristics of APIs in the T-ray region, this technique enables precise, real-time quantification of API concentration without physically separating excipients from the sample. The technique captures comprehensive kinetic profiles, providing deeper insights into dissolution processes and underlying molecular interactions. Its application can enhance Process Analytical Technology (PAT) by facilitating immediate, real-time quality control and supporting continuous manufacturing in the pharmaceutical industry. Additionally, the data generated can strengthen the modeling of <i>in</i> <i>vitro</i>-<i>in vivo</i> correlations (IVIVC), which is crucial for drug development and bioavailability assessment. Overall, the T-ray transmission technique represents a robust, efficient, and sustainable analytical tool for pharmaceutical research and production, offering significant advantages over traditional methods in both accuracy and operational speed.</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 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-026-03515-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918032","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":"An Assessment of In Vitro Permeation Testing Finite Dose Methodology","authors":"Jerry Zhang,&nbsp;David W. Osborne","doi":"10.1208/s12249-026-03514-3","DOIUrl":"10.1208/s12249-026-03514-3","url":null,"abstract":"<div><p>Pharmaceutical emulsifiers used in topical products are either non-ionic surfactants or anionic surfactants. Non-ionic emulsifiers are preferred because they minimally extract epidermal lipids from the stratum corneum (SC) and are well tolerated when applied topically. During topical vehicle development, the Franz diffusion cell allows investigators to determine the amount of drug delivered across the SC after topical application. In this study, we characterized extraction and permeation of 10 naturally occurring SC lipids in excised human skin loaded on a Franz cell 24 h after treatment with 4% sodium lauryl sulfate (SLS) aqueous solution <i>versus</i> neat water. Dermatomed human skin was loaded onto vertical Franz cells and chambers were filled with 0.9% NaCl solution. A 7.5-µL dose of water or 4% SLS aqueous solution was added to each Franz cell. Samples were tape stripped, collected, combined, and extracted with 2.0 mL of 1-hexanol/isopropanol/isopropyl myristate/N-methyl-2-pyrrolidone (15/25/20/40 by volume) overnight at 32°C on an orbit shaker. All 10 lipids were recovered from skin in sufficient amounts to be quantitated by liquid chromatography tandem mass spectrometry. Similar amounts of epidermal lipids were extracted from dermis, epidermis, and SC 24 h after dosing with water or 4% SLS, despite varying demographics of the three donors. For the 10 SC lipids characterized in this study, only ceramides showed lag times for appearing in receptor solution of the Franz cells. This study showed that ceramide NP and NS are suitable markers for epidermal lipid extraction after <i>in vitro</i> permeation testing using finite dosing of dermatomed human skin.</p></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-026-03514-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148917898","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":"Ethosomal Gel–Based Topical Delivery of Albendazole Hydrochloride for Psoriasis: In Vitro and In Vivo Evaluation","authors":"Seda Rençber,&nbsp;Merve Karpuz,&nbsp;Büşra Ünlü Çakıcı,&nbsp;Çinel Köksal Karayıldırım,&nbsp;Emre Özgenç,&nbsp;Evren Gündoğdu,&nbsp;Zeynep Şenyiğit,&nbsp;Fahri Emrah Soylu,&nbsp;Gürkan Yiğittürk","doi":"10.1208/s12249-026-03533-0","DOIUrl":"10.1208/s12249-026-03533-0","url":null,"abstract":"<div><p>This study aimed to develop an albendazole hydrochloride (ALB)-loaded ethosomal gel for topical psoriasis treatment. ALB-loaded ethosomes were prepared and characterized to select the optimal formulation, which was subsequently incorporated into an HPMC-based hydrogel. The ethosomal gel was evaluated through physicochemical, <i>in vitro</i> and <i>in vivo</i> studies. The optimized ethosomal formulation prepared by the film hydration method exhibited a mean vesicle size of 490.00 ± 0.14 nm, polydispersity index of 0.31 ± 0.14, zeta potential of -22.85 ± 2.28 mV and encapsulation efficiency of 23.90 ± 1.43%. After incorporation into the hydrogel matrix, the Gel4-E3/ALB formulation demonstrated appropriate mechanical properties (hardness 8.42 ± 0.70 mN, adhesiveness − 16.85 ± 1.50 mN·s, elasticity 0.89 ± 0.07, cohesiveness 1.14 ± 0.09) and shear-thinning behavior, ensuring ease of application and skin retention. A controlled release pattern was observed, consistent with the controlled-release behavior expected from ethosomal hydrogel systems. Radiolabeling studies demonstrated high labeling efficiency (&gt; 95%). <i>In vitro</i> cytotoxicity evaluation indicated that the optimized ethosomal gel formulation was non-toxic. <i>In vivo</i> studies performed in an imiquimod (IMQ)-induced psoriatic mouse model revealed significant therapeutic improvement in the Gel4-E3/ALB-treated group compared with the IMQ control, with visible reduction in erythema, scaling, and skin thickening after the fifth day of treatment. Hematological analysis showed no adverse effects associated with the formulation. Histopathological evaluation confirmed the reduction in epidermal hyperplasia and inflammatory cell infiltration in the treated group. The developed ALB-loaded ethosomal gel represents a safe and promising topical therapeutic system for psoriasis management.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148917957","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":"From Liquid to Gel: Multifunctional Stimuli-responsive Polymers for Targeted Oral Drug Delivery","authors":"Manoj Kumar Mishra,&nbsp;Divaker Shukla,&nbsp;Shalini Sharma,&nbsp;Jyoti Nanda Sharma,&nbsp;Tej Pratap Singh","doi":"10.1208/s12249-026-03519-y","DOIUrl":"10.1208/s12249-026-03519-y","url":null,"abstract":"<div><p>Oral drug delivery is the delivery method of choice, as it is non-invasive and patients will comply with the delivery method, but many contemporary therapeutics, such as poorly soluble, permeable, and unstable drugs, fail because of rapid gastrointestinal absorption, enzyme degradation, and non-targetability. The <i>in-situ</i> gelling systems are now considered paradigms that no longer exist as liquids; instead, they form a depot in the gastrointestinal tract and transform into a gel in response to physiological signals such as pH, ions, or enzymes. This review will discuss how these so-called smart polymers have developed over the years, starting as simple gel-forming systems and evolving into the multifunctional platforms that are also designed to have a pointed and sustained action. Next generation in situ gels combine bioadhesion, permeation enhancement, and active targeting ligands to overcome sequential barriers to delivery transit, permeability, stability, and cellular uptake. We critically assess the chemistry, mechanisms, formulation strategies, and therapeutic use of these systems, including gastro-retention and localized therapy, as well as oral delivery of biologics. Despite encouraging preclinical results, we touch on translational issues of scalability, manufacturing, and regulatory pathways. Multifunctional stimuli-responsive polymers, which actively traverse the gastrointestinal environment, are the future of oral drug delivery because they provide precision, bioavailability, and improved patient outcomes.</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 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148917989","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":"Solid Lipid Nanoparticles Based Dry Powder Inhalers for Enhanced Drug Delivery Against Lung Diseases","authors":"Cagla Onel,&nbsp;Yagmur Pirincci Tok,&nbsp;Yildiz Ozsoy","doi":"10.1208/s12249-026-03513-4","DOIUrl":"10.1208/s12249-026-03513-4","url":null,"abstract":"<div><p>The global incidence of lung diseases associated with high mortality and morbidity rates is projected to rise in the coming years. Conventional therapies face limitations such as low bioavailability and systemic side effects with oral administration, as well as poor patient compliance and frequent dosing with traditional inhalers. These shortcomings have created an urgent need for novel pulmonary drug delivery systems. In recent years, nanoparticulate drug carriers have gained significance for their potential to enable targeted lung delivery and reduced dosing frequency. Among them, solid lipid nanoparticles (SLNs) have attracted considerable attention due to their biocompatible and biodegradable structures, controlled release capabilities, organic solvent-free production processes and favorable aerodynamic behavior. This review provides a comprehensive perspective to guide the rational design of SLN-based dry powder inhaler (DPI) systems by integrating formulation strategies, production techniques, surface functionalization, and DPI development, with the goal of enhancing therapeutic outcomes in respiratory diseases such as cancer, infections, chronic obstructive pulmonary disease, and cystic fibrosis.</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 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918068","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":"Correlative Spectroscopic and Structural Imaging for Resin-Embedded Extended-Release Morphine Sulfate Pellets","authors":"Yeakub Zaker,&nbsp;Snober Ahmed,&nbsp;Li Tian,&nbsp;Huzeyfe Yilmaz,&nbsp;Changning Guo,&nbsp;Jason D. Rodriguez,&nbsp;Daniel R. Willett","doi":"10.1208/s12249-026-03521-4","DOIUrl":"10.1208/s12249-026-03521-4","url":null,"abstract":"<div><p>Correlative spectroscopic and structural imaging provides a powerful approach for characterizing the microstructure of complex pharmaceutical formulations. Laser direct infrared (LDIR) spectroscopy is an emerging, rapid spectroscopic imaging technique that complements traditional approaches by enabling non-destructive chemical and morphological analysis over large sample surfaces within minutes. In this study, the capabilities of LDIR imaging were evaluated alongside Raman mapping, SEM–EDS, laser microscopy, and micro-CT as part of a correlative workflow to characterize the microstructure and chemical composition of pharmaceutical pellets. Resin embedding enabled consistent handling and structural preservation of extended-release pharmaceutical pellets across all imaging modalities. Two commercially available morphine sulfate ER pellets (ER-1 and ER-2) with different excipient compositions were used as model systems. Laser microscopy revealed distinct differences in surface topography, while micro-CT performed before milling confirmed inherent structural features. ER-1 displayed a smooth, intact core, whereas ER-2 exhibited internal cracks and cavities. Hyperspectral LDIR imaging successfully identified major components in both formulations (hit-quality index, HQI ≥ 0.83) with strong concordance to Raman mapping (HQI ≥ 0.85). The spatial distribution of the active pharmaceutical ingredient (API) revealed a layered structure in ER-1 and a homogeneous core in ER-2. This correlative workflow, combining resin embedding with multiple imaging modalities, underscores the value of LDIR and complementary techniques for comprehensive physicochemical characterization of complex drug products. These findings highlight the utility of correlative imaging for regulatory assessment and quality control of complex extended-release formulations.</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 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148917896","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}