International Journal of Pharmaceutics最新文献

{"title":"Orodispersible films prepared by hot-melt extrusion versus solvent casting.","authors":"Mathieu Reuther, Nicolas Rollet, Frédéric Debeaufort, Odile Chambin","doi":"10.1016/j.ijpharm.2025.125536","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2025.125536","url":null,"abstract":"<p><p>This study investigated the influence of solvent casting and hot-melt extrusion manufacturing methods on the physical, chemical, and functional properties of orodispersible films with the same composition and incorporating a poorly soluble active pharmaceutical ingredient (API). Both techniques produced films that met pharmaceutical standards for disintegration and dissolution times. Solvent casting, the most used method, yielded films with homogeneous distribution of plasticizer, smoother textures, and greater flexibility. In contrast, hot melt extrusion, a solvent-free process, resulted in slightly brittle films due to uneven plasticizer integration, highlighting the impact of manufacturing parameters on film structure. Despite these differences, both methods exhibited similar chemical stability under varying humidity conditions, with API recrystallization occurring at higher humidity, particularly in films prepared by solvent casting. Increased humidity significantly reduced tensile strength, as water acted as a plasticizer, promoting API recrystallization and weakening the structure. Stability tests revealed that hot melt extrusion films retained their structural and chemical integrity over 12 months when stored in impermeable packaging bags. This study confirms the suitability of hot melt extrusion for industrial-scale ODF production, offering advantages such as a solvent-free process, reduced environmental impact, and adaptability for modern pharmaceutical manufacturing, provided formulation and process parameters could be carefully optimized.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"125536"},"PeriodicalIF":5.3,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Self-assembled PAMAM-G4 dendrimer nanoparticles with Phloxine B as photosensitizer for antimicrobial photodynamic therapy","authors":"David E. Ybarra ,&nbsp;Camila Quezada ,&nbsp;Yuly A. Guarín ,&nbsp;Gerardo A. Cabello ,&nbsp;Jorge Montanari ,&nbsp;Fernando C. Alvira ,&nbsp;Silvia del Valle Alonso ,&nbsp;Manuel F. Meléndrez ,&nbsp;Luis F. Barraza","doi":"10.1016/j.ijpharm.2025.125534","DOIUrl":"10.1016/j.ijpharm.2025.125534","url":null,"abstract":"<div><div>Antimicrobial resistance (AMR) represents a critical global health challenge, driving the need for innovative therapeutic strategies. This study introduces self-assembled nanoparticles based on fourth-generation polyamidoamine (PAMAM-G4) dendrimers and Phloxine B (PhB), forming G4-PhB nanoparticles as an advanced platform for antimicrobial photodynamic therapy (aPDT). The optimal dendrimer:dye molar ratio was determined through dynamic light scattering (DLS) titration experiments, yielding a 1:15 G4:PhB ratio. The resulting G4-PhB nanoparticles were spherical, with a hydrodynamic diameter of 260 ± 15 nm, a narrow polydispersity index (PDI) of 0.264 ± 0.085, and a positive zeta potential of 8.71 ± 2.88 mV, indicating monodispersity and colloidal stability. These features were corroborated by morphological analyses using TEM and AFM. Cytotoxicity assays conducted on murine fibroblasts (3 T3 cell line), using MTT, neutral red uptake, and crystal violet staining revealed that G4-PhB nanoparticles are intrinsically non-toxic, contrasting with the EDTA-PhB complex, which exhibited significant cytotoxic effects. Antibacterial activity was evaluated against <em>Staphylococcus aureus</em> (SA) and <em>Pseudomonas aeruginosa</em> (PA). While free PhB demonstrated bactericidal effects exclusively against SA, the G4-PhB nanoparticles exhibited enhanced activity against both bacterial strains, notably overcoming the limitations of free PhB against PA. These findings highlight the versatility and effectiveness of G4-PhB nanoparticles as a biocompatible and non-invasive system for localized aPDT, with potential applications in wound healing for immunocompromised patients. This work provides a robust foundation for future research into dendrimer-based photosensitizers as innovative solutions to pressing biomedical challenges.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"675 ","pages":"Article 125534"},"PeriodicalIF":5.3,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A review on design rules for formulating amorphous solid dispersions based on drug-polymer interactions in aqueous environment","authors":"Gayathri Ramachandran ,&nbsp;Indhu Annie Chacko ,&nbsp;M.G. Mishara ,&nbsp;Ajay Jaysingh Khopade ,&nbsp;M. Sabitha ,&nbsp;M.S. Sudheesh","doi":"10.1016/j.ijpharm.2025.125541","DOIUrl":"10.1016/j.ijpharm.2025.125541","url":null,"abstract":"<div><div>Amorphous solid dispersions (ASDs) are multi-component formulations in which a drug is molecularly dispersed in a carrier. ASDs undergo complex dissolution mechanisms to generate and sustain a supersaturated state of poorly soluble drugs. The link between enhanced solubility, supersaturation stability and drug-polymer interaction (DPI) is critical for the rational design of ASDs. The key mechanism responsible for a high bioavailability is the evolution of supersaturation during the dissolution of ASDs which is also the driving force for drug precipitation. A critical determinant of robust supersaturation generation and stability during dissolution is the molecular interaction between the drug and polymer. Characterization of DPI in a solution state is, however, challenging because of the poor hydrodynamic resolution of the techniques, traditionally used in solid-state analysis. Further, the dissolution conditions, such as the choice of buffer, pH and ionic strength may complicate the analyses and predictions. The role of DPI is a poorly understood aspect of ASD dissolution and therefore is an active area of research. DPI is critical for understanding the design rules for formulating an optimal ASD formulation. The review focuses on different aspects of DPI to stabilize the supersaturated state of a drug during the dissolution of ASDs.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"675 ","pages":"Article 125541"},"PeriodicalIF":5.3,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aging-induced microstructural evolution in risperidone loaded PLGA microspheres.","authors":"Andrew G Clark, Jeffery Wong, Ruifeng Wang, Yan Wang, Bin Qin, Diane J Burgess, Shawn Zhang","doi":"10.1016/j.ijpharm.2025.125512","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2025.125512","url":null,"abstract":"<p><p>This study demonstrates the application of innovative imaging-based characterization techniques to quantify structural changes as a function of ageing for poly (lactic-co glycolic acid) (PLGA) microspheres. Aging of polymers can potentially alter the performance of polymer-based therapeutics and therefore an understanding of the impact of aging on microsphere structure is important. Correlative focused ion beam scanning electron microscopy (FIB-SEM) and X-ray microscopy (XRM) were used to quantify the change in structural critical quality attributes (CQAs) of risperidone loaded microspheres at the single microsphere scale and overall batch scale. One batch of microspheres was aged one year beyond its shelf life while the other batch was within its shelf life, providing a robust comparison between an aged and fresh sample. Comparison of the aged and fresh microspheres revealed an increase in porosity and pore size following aging at the nanoscale, anticipated with physical relaxation of the PLGA. A novel XRM-based method to determine the material density of the microsphere batches was employed to assess the batch level changes induced by aging. A decrease in density in the aged microsphere batch was observed, that was consistent with the porosity increase seen in the FIB-SEM study. These results reveal aging produces an increase in porosity through polymer relaxation that widens the existing pores within the microspheres. The increased porosity was correlated to the in vitro release performance of the two microsphere batches, providing a novel method to assess the impact of polymer aging on the downstream performance of PLGA microsphere systems.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"125512"},"PeriodicalIF":5.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural deep eutectic solvents (NADES) in drug delivery systems: Characteristics, applications, and future perspectives","authors":"Hui Li ,&nbsp;Kaining Yang ,&nbsp;Yumin Yang ,&nbsp;Liqin Ding ,&nbsp;Xiaoxia Li","doi":"10.1016/j.ijpharm.2025.125509","DOIUrl":"10.1016/j.ijpharm.2025.125509","url":null,"abstract":"<div><div>Deep eutectic solvents (DESs) are a class of low-melting mixtures formed by the hydrogen-bond interactions between hydrogen bond acceptors (HBAs) and hydrogen bond donors (HBDs) in specific molar ratios. Their unique physicochemical properties enable DESs to significantly enhance drug solubility and permeability, while also serving as carriers to facilitate efficient drug delivery. A subclass of DESs, natural deep eutectic solvents (NADESs), is found in the metabolites of natural organisms, such as plants. With low toxicity and biodegradability, NADESs possess distinct advantages for applications in the pharmaceutical field.The therapeutic efficacy of drugs is often limited by imprecise release mechanisms, leading to the metabolism or degradation of a portion of the drug before it reaches the target site, thereby reducing its effectiveness. Moreover, many drugs exhibit poor solubility and stability, resulting in low efficiency during absorption and metabolism, which further diminishing their therapeutic impact. NADESs, with their excellent tunability and biocompatibility, have demonstrated great potential in drug delivery systems.This paper first provides an overview of the fundamental characteristics of NADESs, followed by a detailed summary of recent advancements and applications of NADESs across various administration routes, including transdermal, mucosal, and inhalation drug delivery. Finally, the paper explores the prospects of NADESs in novel drug delivery systems and proposes strategies for optimizing their performance to promote clinical applications.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"675 ","pages":"Article 125509"},"PeriodicalIF":5.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A self-assembly enzyme-like hydrogel with ROS scavenging and immunomodulatory capability for microenvironment-responsive wound healing acceleration","authors":"Xiaohui Jia ,&nbsp;Yuhe Dong ,&nbsp;Jihui Lu ,&nbsp;Zhenyuan Yang ,&nbsp;Ran Xu ,&nbsp;Xiang Zhang ,&nbsp;Jingyi Jiao ,&nbsp;Zixuan Zhang ,&nbsp;Yixuan Lin ,&nbsp;Fuhao Chu ,&nbsp;Penglong Wang ,&nbsp;Tian Zhong ,&nbsp;Haimin Lei","doi":"10.1016/j.ijpharm.2025.125529","DOIUrl":"10.1016/j.ijpharm.2025.125529","url":null,"abstract":"<div><div>On-demand responsive hydrogels are a promising solution for effective wound management as they can adjust their properties in response to changes in the wound environment, allowing them to provide tailored support for the healing process. However, the conventional hydrogels may not fully meet the diverse demands of the intricate healing process. Herein, a novel glycyrrhizic acid (GA) based self-assembly hydrogel coordinated with copper and polyphenol (GCP hydrogel) was developed to exhibit triggered release behavior in response to the microenvironment. The GCP hydrogel coordinated with copper and protocatechuic acid (PA) and self-assembled with GA, also exhibits enzyme-like properties by mimicking the cascade process of superoxide dismutase (SOD) and catalase (CAT), effectively scavenging reactive oxygen species (ROS). Furthermore, the on-demand release of Cu²⁺ at different stages of the wound healing process can not only enhance the antibacterial ability of methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) but also intelligently promote angiogenesis with outstanding biocompatibility. In addition, the GCP hydrogel effectively modulated the activity of macrophages in response to inflammatory stimuli, exhibiting remarkable anti-inflammatory abilities and promoting tissue regeneration. The multifunctional GCP hydrogel platform has the potential to create a dynamic microenvironment that is conducive to tissue regeneration, making it an ideal candidate for smart wound management.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"675 ","pages":"Article 125529"},"PeriodicalIF":5.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D printing of partially-coated floating systems for controlled release of drugs into the stomach","authors":"Marco Uboldi ,&nbsp;Arianna Chiappa ,&nbsp;Francesco Briatico-Vangosa ,&nbsp;Alice Melocchi ,&nbsp;Lucia Zema","doi":"10.1016/j.ijpharm.2025.125513","DOIUrl":"10.1016/j.ijpharm.2025.125513","url":null,"abstract":"<div><div>This work focused on the development of a retentive drug delivery system (DDS) able to float in the gastric fluids and to ensure prolonged release of drugs over a pre-defined period of time, being then safely emptied from the stomach. To this end, the design step played a pivotal role. The device was thus devised to be composed of a polyvinyl alcohol-based matrix with a tapered geometry, which was partially coated with an insoluble layer of thermoplastic elastomer. This way, release of allopurinol (ALP), used as model drug, could occur only from the uncoated surfaces, while the peculiar geometry of the hydrophilic swellable/erodible matrix was intended to balance the increase in the diffusional path over time with a wider release area. In addition, the coating featured air pockets, whose volume was sized to compensate for the weight force of the DDS once immersed in gastric fluids, thus ensuring its long-lasting buoyancy. By easing the entrance of gastric fluids when the matrix is completely exhausted, such air pockets would also favor sinking and removal of the DDS from the pylorus. Given the multi-layered geometry of the final floating device, including hard-to-fabricate details (<em>e.g.</em> uncoated surfaces, voids), fused deposition modeling 3D printing was identified as the technique of choice for its effectiveness in manufacturing complex shapes. Various formulations were tested for fabricating both the inner matrix and the outer coating, assessing their thermo-mechanical properties, printability and release behavior. The gastro-retentive system demonstrated prolonged buoyancy (&gt; 12 h) and a wide portfolio of ALP release performances, differing in rate and duration, which would make it a promising platform for personalized delivery of drugs in the upper gastrointestinal tract.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"675 ","pages":"Article 125513"},"PeriodicalIF":5.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced targeted cytotoxic and apoptotic effects of docetaxel by enzyme-mediated controlled release system based on cyclodextrin/maltogenic amylase.","authors":"Zahra Sattari, Simin Dadashzadeh, Soraya Shahhosseini, Reza H Sajedi","doi":"10.1016/j.ijpharm.2025.125533","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2025.125533","url":null,"abstract":"<p><p>A novel system has been developed for the controlled release of docetaxel (DTX), an anticancer agent, utilizing β-cyclodextrin (β-CD) and maltogenic amylase (MAase) as the cyclodextrinase (CDase). In this study, we describe the creation of a targeted drug delivery system by conjugating MAase to a glutamate-urea-lysine (EUK) mimetic dipeptide, which acts as a ligand specific to the prostate-specific membrane antigen (PSMA), a crucial target for prostate cancer treatment. The conjugation of MAase and EUK was facilitated by dextran, as confirmed by dynamic light scattering (DLS). Additionally, we prepared a β-CD-DTX inclusion complex, which was validated using UV-visible (UV-vis) spectrophotometry and Fourier-transform infrared (FT-IR) spectroscopy, resulting in an encapsulation efficiency of 31.43. In vitro studies indicated that the β-CD-DTX/MAase-EUK bioconjugate displayed enhanced cytotoxicity against LNCaP cells, which express high levels of PSMA, with a half-maximal inhibitory concentration (IC₅₀) of 34 nM after 48 h significantly lower than the 60 nM IC₅₀ associated with the β-CD-DTX/MAase system. Flow cytometric analysis revealed that the bioconjugate notably increased apoptotic rates compared to alternative formulations, showing early apoptosis at 28.2 % and late apoptosis at 14.2 %. Furthermore, activation of caspase-3/7 was significantly heightened in LNCaP cells treated with the β-CD-DTX/MAase-EUK system. These results indicate that the targeted delivery system enhances the solubility and bioavailability of DTX, thereby improving its therapeutic efficacy against prostate cancer while mitigating systemic toxicity.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"125533"},"PeriodicalIF":5.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening and preparation of curcumin nano-formulations combined with dissolving microneedles on the application in the effective treatment of psoriasis","authors":"Peng Xu ,&nbsp;Kun Xu ,&nbsp;Jiayin Li ,&nbsp;Aoxue Liu ,&nbsp;Wei Xiao ,&nbsp;Lin Sun","doi":"10.1016/j.ijpharm.2025.125528","DOIUrl":"10.1016/j.ijpharm.2025.125528","url":null,"abstract":"<div><div>Psoriasis, a prevalent immunoinflammatory skin condition, is characterized by abnormal skin thickening, which complicates traditional topical drug delivery and hinders drug penetration. Our goal is to enhance the efficacy of psoriasis treatment by developing a transdermal drug formulation. Microneedles (MNs) can improve treatment outcomes by increasing the absorption of topical medications through skin penetration. Curcumin (Cur), a natural anti-inflammatory, antioxidant, and immunomodulatory small molecule with water-insoluble properties, shows promise for psoriasis relief. In this research, three Cur nano-formulations (NFs) were screened and prepared using antisolvent and ethanol injection methods, with one being dispersed into hyaluronic acid (HA) dissolving MNs. A transdermal nano-MNs delivery system was constructed using a double-layer centrifugation technique. This co-delivery system overcame Cur’s solubility issues, poor absorption, and instability, allowing targeted and efficient delivery of Cur-NFs to the skin without being hindered by the skin barrier. <em>In vitro</em> studies demonstrated that Cur-NF dissolving MNs possess adequate mechanical properties for skin implantation, exhibit rapid dissolution, and achieve an effective drug release rate of 73 % within 6 h. Pharmacodynamic evaluations demonstrated that the MNs system effectively ameliorated key psoriatic skin manifestations. Notably, MNs treatment significantly reduced the Psoriasis Area and Severity Index (PASI) score from 12.0 ± 0.0 (model group) to 4.7 ± 0.5 (<em>p</em> &lt; 0.05), alongside a marked suppression of pro-inflammatory cytokines, including TNF-α, IL-17, IL-22, and IL-23, compared to untreated psoriatic controls. Therefore, the composite dissolving MNs delivery system loaded with Cur-NFs represents a promising approach for psoriasis treatment.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"675 ","pages":"Article 125528"},"PeriodicalIF":5.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and adhesion evaluation of transdermal rotigotine patches utilizing 3D-printed skin-mimicking substrate, solid-state NMR, and ATR-FTIR techniques.","authors":"Arvind Bagde, Keb Mosley-Kellum, Sungsool Wi, Nisarg Modi, Satyanarayan Dev, Mandip Singh","doi":"10.1016/j.ijpharm.2025.125522","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2025.125522","url":null,"abstract":"<p><p>Transdermal rotigotine patches, used to treat parkinson's disease, often face challenges in maintaining adequate adhesion, which is crucial for effective drug delivery. Adhesion performance is influenced by environmental conditions such as humidity and temperature, as well as skin characteristics like wrinkles and micro-delaminations that vary with age and sex. Standard adhesion tests using stainless steel (SS) substrates do not accurately mimic human skin, leading to overestimated adhesion strength. This study developed rotigotine matrix transdermal formulations with silicone pressure sensitive adhesive (PSA) and evaluated their adhesion properties at 32 ± 1°C and 75 ± 5 % RH in a stability chamber. Moisture uptake over 24 h was measured using solid-state nuclear magnetic resonance (SSNMR) spectroscopy and attenuated total reflectance-fourier transform infrared- (ATR-FTIR) spectroscopy. Adhesion tests, including probe tack and peel, were performed on SS and 3D-printed acrylonitrile butadiene styrene (ABS) substrates designed with micro-delaminations and wrinkles to simulate skin conditions. In vitro permeation testing (IVPT) studies demonstrated a flux of 10.48 ± 0.61 and 10.03 ± 0.57 μg/h/cm² for formulations with and without mannitol, respectively. SSNMR and ATR-FTIR revealed significant moisture uptake, contributing to adhesion loss. Adhesion forces were significantly lower on ABS compared to SS, with further reductions observed on wrinkled and micro-delaminated surfaces, indicating that SS substrates overestimate adhesion results. This is the first study to combine SSNMR and skin-mimetic substrates for analyzing adhesion loss in transdermal patches, highlighting the potential of moisture-resistant agents like mannitol to enhance patch performance.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"125522"},"PeriodicalIF":5.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}