Pharmaceutics最新文献

{"title":"Improving Alzheimer's Disease and Parkinson's Disease in Rats with Nanoemulsion and Byproducts Prepared from Cinnamon Leaves.","authors":"Bing-Huei Chen, Chen-Te Jen, Chia-Chuan Wang, Min-Hsiung Pan","doi":"10.3390/pharmaceutics17091200","DOIUrl":"10.3390/pharmaceutics17091200","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Cinnamon leaves, an important source of the functional compound cinnamaldehyde (CA), have been shown to be effective in improving type II diabetes and Parkinson's disease (PD) in rats following the incorporation of cinnamon leaf extract into a nanoemulsion. However, the effect of a cinnamon leaf extract nanoemulsion (CLEN) on improving Alzheimer's disease (AD), the most prevalent type of dementia, remains unexplored. The objectives of this study were to determine functional compounds in cinnamon leaves by UPLC-MS/MS, followed by the preparation of a nanoemulsion and its byproducts to study their effects on AD and PD in rats. <b>Methods</b>: Oven-dried (60 °C for 2 h) cinnamon leaf powder and hydrosol, obtained by steam distillation of cinnamon leaf powder, were stored at 4 °C. After determination of basic composition (crude protein, crude fat, carbohydrate, moisture and ash) of cinnamon leaf powder, it was extracted with 80% ethanol with sonication at 60 °C for 2 h and analyzed for bioactive compounds by UPLC-MS/MS. Then, the CLEN was prepared by mixing cinnamon leaf extract rich in CA with lecithin, soybean oil, tween 80 and ethanol in an optimal ratio, followed by evaporation to form thin-film and redissolving in deionized water. For characterization, mean particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency, and surface morphology were determined. Animal experiments were done by dividing 90 male rats into 10 groups (n = 9), with groups 2-8 being subjected to mini-osmotic pump implantation surgery in brain to infuse Amyloid-beta 40 (Aβ40) solution in groups 2-8 for induction of AD, while groups 9 and 10 were pre-fed respectively with cinnamon powder in water (0.5 g/10 mL) and in hydrosol for 4 weeks, followed by induction of AD as shown above. Different treatments for a period of 4 weeks included groups 1-9, with group 1 (control) and group 2 feeding with sterilized water, while groups 3, 4 and 5 were fed respectively with high (90 mg/kg), medium (60 mg/kg) and low (30 mg/kg) doses of cinnamon leaf extracts, groups 6, 7 and 8 fed respectively with high (90 mg/kg), medium (60 mg/kg) and low (30 mg/kg) doses of nanoemulsions, groups 9 and 10 fed respectively with 10 mL/kg of cinnamon powder in water and hydrosol (0.5 g/10 mL). Morris water maze test was conducted to determine short-term memory, long-term memory and space probing of rats. After sacrificing of rats, brain and liver tissues were collected for determination of Aβ40, BACE1 and 8-oxodG in hippocampi, and AchE and malondialdehyde (MDA) in cortices, antioxidant enzymes (SOD, CAT, GSH-Px) and MDA in both cortices and livers, and dopamine in brain striata by using commercial kits. <b>Results</b>: The results showed that the highest level of CA (18,250.7 μg/g) was in the cinnamon leaf powder. The CLEN was prepared successfully, with an average particle size of 17.1 nm, a polydispersity index of 0.236, a zeta potential of -42","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177335","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":"Development of Timed Release Vaginal Mucosal Cloprostenol for Farrowing Management in Sows.","authors":"Ahm Musleh Uddin, Preechaphon Taechamaeteekul, Kiro R Petrovski, Padet Tummaruk, Yunmei Song, Sanjay Garg, Roy N Kirkwood","doi":"10.3390/pharmaceutics17091198","DOIUrl":"10.3390/pharmaceutics17091198","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Controlling the timing of farrowing to occur during working hours presents an opportunity to improve supervision and reduce piglet neonatal mortality. However, the use of non-therapeutic injectable drugs is often limited in commercial swine production. This study aimed to develop a cloprostenol vaginal mucosal delivery system for induction of farrowing. To achieve this, two vaginal tablets containing cloprostenol were formulated for simultaneous insertion: an immediate-release (IR) tablet and a delayed release (DR) tablet, the latter designed for a 6 h delay before release. <b>Methods:</b> In vitro release studies demonstrated that the IR tablet released 100% of the drug within 5 min, while the DR tablet, initiated release after four hours and achieved approximately 80% release at six hours, aligning with the targeted release profile. To evaluate the efficacy of the optimized formulations, an in vivo study was conducted using 121 mixed parity Landrace × Large White sows that were assigned to one of four treatments, control (n = 23) received no treatment; IM (n = 26) received 185 µg of cloprostenol via intramuscular injection; IR (n = 36) received a 100 µg IR tablet by vaginal deposition; and IR + DR (n = 36) received both IR and DR tablets by vaginal deposition, to simulate split-dose delivery. <b>Results:</b> Control sows experienced longer (<i>P</i> < 0.001) intervals to farrowing compared to those receiving cloprostenol treatments. Additionally, differences (<i>P</i> < 0.05) were observed in interval from treatment to farrowing time among the treatments, with the interval for IM sows being shorter than for IR (<i>P</i> < 0.001) and IR + DR (<i>P</i> = 0.001) sows. <b>Conclusions:</b> These findings confirm that the vaginal route offers an alternative, non-invasive, method for farrowing induction in sows, facilitating farrowing supervision during working hours and potentially reducing piglet mortality.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177390","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":"Anti-Psoriatic Pharmacodynamic Material Basis of Dictamni Cortex Based on Transdermal Constituents Group.","authors":"Zhaoyu Wang, Mengting Pi, Ziang Gao, Maobo Du, Liwei Gu, Shuzhi Liu, Shuo Shen","doi":"10.3390/pharmaceutics17091195","DOIUrl":"10.3390/pharmaceutics17091195","url":null,"abstract":"<p><p><b>Background:</b> Psoriasis is a chronic inflammatory skin disorder for which topical medications are the preferred treatment option. However, current therapies are limited by adverse reactions, drug resistance, and economic burdens. Dictamni Cortex (DC; the root bark of <i>Dictamnus dasycarpus</i> Turcz.) has a long history in the treatment of psoriasis, with its transdermal bioactive constituents serving as the pharmacodynamic foundation for topical anti-psoriatic therapy. <b>Methods:</b> Building on the separation of DC's chemical constituents, this study integrated ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and network pharmacology, along with activity verification, to investigate the anti-psoriatic active components among the transdermal constituents of DC. <b>Results:</b> Forty-one chemical constituents were characterized in DC, including 26 transdermally permeable compounds, predominantly alkaloids and limonoids. Network pharmacological analysis revealed core targets, including MMP9 and TLR4, as well as multiple pathways related to inflammatory and immune responses. Molecular docking studies identified dictamnine, jangomolide, rutaevin, and other key transdermal constituents that exhibited high binding affinity to core targets. In vitro validation showed that these compounds significantly suppressed cellular proliferation (<i>p</i> < 0.05) and downregulated Ki67 mRNA expression (<i>p</i> < 0.05) in the psoriasis-like HaCaT cell model. Concurrently, they significantly reduced secretion of key pro-inflammatory cytokines, including IL-17A, IL-22, IL-1β, IL-6, and IL-8 (<i>p</i> < 0.05). Comprehensive comparative analyses confirmed that dictamnine exhibited ideal anti-psoriatic efficacy. <b>Conclusions:</b> These results provide a pharmacological substance basis for the development of external preparations of DC for treating psoriasis and provide novel research concepts for investigating the pharmacodynamic material basis of Traditional Chinese Medicine topical drugs.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177441","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":"Examining the Impact of Storage Conditions on the Stability of a Liquid Formulation of mRNA-Loaded Lipid Nanoparticles.","authors":"Mina Sato, Eleni Samaridou, Moritz Beck-Broichsitter, Masatoshi Maeki, Shunsuke Kita, Manabu Tokeshi, Katsumi Maenaka, Hideyoshi Harashima, Yusuke Sato","doi":"10.3390/pharmaceutics17091194","DOIUrl":"10.3390/pharmaceutics17091194","url":null,"abstract":"<p><p><b>Background/Objectives</b>: This study investigated the effect of storage conditions on mRNA-LNPs in situ via identification of the formulation traits necessary for improving storage stability. <b>Methods</b>: We synthesized an ionizable lipid, namely TOT-28, which has a hydrolysis-susceptible ester bond in its hydrophilic head group that allows it to act as an indicator of the hydrophilic environment within the mRNA-LNPs. LNPs were stored either at 4 or 25 °C for up to 8 weeks to investigate the effect of pH and temperature on ester hydrolysis, internal mRNA integrity, physicochemical properties of the LNPs, and mRNA gene expression. <b>Results</b>: The results indicate that, at 25 °C, a lower buffer pH increases ester hydrolysis, whereas an opposite trend slightly occurs in ester hydrolysis with storage at 4 °C. We also found that TOT-28-based LNPs were less hydrated and microviscosity was higher at 4 °C compared with storage temperature at 25 °C. Therefore, TOT-28-based LNPs seem less sensitive to external buffer solutions because of a higher-order structure when stored at lower temperatures. In addition, we found that LNPs with different ionizable lipid structures exhibit distinct responses to pH changes at specific storage temperatures. <b>Conclusions</b>: Our findings provide novel insights into the appropriate conditions for long-term storage of the mRNA-LNPs as a liquid formulation.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177505","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":"Improved Dual-Modality Bioequivalence Evaluation of Topical Formulations Within Human Skin Using Stimulated Raman Scattering Microscopy.","authors":"Dandan Tu, Nick-Sidney Lemberger, Kristin Wallmeier, Jackson Riseman, Benjamin A Kuzma, Yuxiao Wei, Ting Chean Khoo, Elena Rantou, Priyanka Ghosh, Markham C Luke, Sam G Raney, Carsten Fallnich, Conor L Evans","doi":"10.3390/pharmaceutics17091193","DOIUrl":"10.3390/pharmaceutics17091193","url":null,"abstract":"<p><p><b>Background:</b> The use of optical microscopic techniques has gained increasing attention in recent years for studying the bioavailability (BA) and bioequivalence (BE) of topical drugs. Stimulated Raman scattering (SRS), one type of optical imaging technique, probes chemical-specific information and has excellent spatiotemporal resolution. It uses intrinsic molecular vibrational signatures, and therefore, labeling samples or other treatments is unnecessary to track a molecule. Because of its unique advantages, studies have used SRS for BA evaluations and, more recently, for BE evaluations. In BE evaluation, low data variance within a treatment group is important to ensure sensitivity and specificity in comparing treatment groups. <b>Methods:</b> When measuring forward-direction SRS signals transmitted through skin, the signal intensity is susceptible to variance due to several factors, such as the microscope system's performance, the different optical features of topical drug products, and the heterogeneity of skin in transmitting light. This work closely investigated the effects of these factors on an SRS signal and developed solutions to reduce their effects on the data variance. Specifically, we constructed a method using a dual-modality detector built in-house, which simultaneously measured both the SRS signal and total light transmission synchronized in time and co-registered in space. <b>Results:</b> We developed equations to normalize SRS signals using the transmission intensity, and the results demonstrated a clear improvement in the SRS signal via a reduction in the signal variance (up to a 9.46% CV value decrease) that is otherwise caused by various factors associated with the use of topical drugs and the composition of the skin. We carried out an exploratory BE study using tretinoin-containing topical products and observed improvements in BE assessment with the developed method (could achieve a reduction of 0.11 in the CI value). <b>Conclusions:</b> This work has led to a better understanding of the factors that affect SRS imaging and has provided an effective method to compensate for these factors in BE assessments. This is a critical initial effort for better practical implementation of SRS in cutaneous pharmacokinetics (cPKs) studies of topical drugs.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177358","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":"Recent Advances in Supramolecular Systems for Precision Medicine: Structural Design, Functional Integration, and Clinical Translation Challenges.","authors":"Xiaomin Ma, Yazhe Xiao, Shuyu Li, Jianghai Du, Junjie Wang, Xingzhou Peng","doi":"10.3390/pharmaceutics17091192","DOIUrl":"10.3390/pharmaceutics17091192","url":null,"abstract":"<p><p>Non-covalent and dynamic covalent interactions enable supramolecular systems to function as adaptive platforms in biomedical research, offering novel strategies for precision medicine applications. This review examines five-year developments in supramolecular applications across precision medical domains, including disease diagnosis, bioimaging, targeted drug delivery, tissue engineering, and gene therapy. The review begins by systematically categorizing supramolecular structures into dynamic covalent systems (e.g., disulfide bonds, boronate esters, and hydrazone bonds) and dynamic non-covalent systems (e.g., host-guest interactions, hydrogen-bond networks, metal coordination, and π-π stacking), highlighting current strategies employed to optimize their responsiveness, stability, and targeting efficiency. Representative case studies, such as cyclodextrin-based nanocarriers and metal-organic frameworks (MOFs), are thoroughly analyzed to illustrate how supramolecular systems can enhance precision in drug delivery and improve biocompatibility. Furthermore, this article critically discusses major challenges faced during clinical translation, encompassing structural instability, inadequate specificity of environmental responsiveness, pharmacokinetic and toxicity concerns, and difficulties in scalable manufacturing. Potential future directions to overcome these barriers are proposed, emphasizing biomimetic interface engineering and dynamic crosslinking strategies. Collectively, the continued evolution in structural optimization and functional integration within supramolecular systems holds great promise for achieving personalized diagnostic and therapeutic platforms, thereby accelerating their translation into clinical practice and profoundly shaping the future landscape of precision medicine.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177474","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":"Sustained-Release Biodegradable Intracameral Implants Containing Dexamethasone and Moxifloxacin: Development and In Vivo Primary Assessment.","authors":"Pablo Miranda, Luis Ignacio Tártara, Analía Castro, Patricia Zimet, Ricardo Faccio, Santiago Daniel Palma, Álvaro W Mombrú, Helena Pardo","doi":"10.3390/pharmaceutics17091191","DOIUrl":"10.3390/pharmaceutics17091191","url":null,"abstract":"<p><p><b>Background/Objectives</b>: We report the development of a novel intraocular sustained-release implantable pharmaceutical formulation, designed to be placed in the anterior chamber of the eye after cataract surgery. The device is intended to reduce postoperative inflammation, and to prevent opportunistic bacterial infections that may lead to endophthalmitis. <b>Methods</b>: The implants were produced via hot-melt extrusion, using a twin-screw extruder to process a homogeneous mixture of polylactide-co-glycolic acid, moxifloxacin hydrochloride (MOX HCl) and dexamethasone (DEX). Quality control tests included drug content determination, release rate profile evaluation, and several instrumental characterization techniques (scanning electron microscopy (SEM), confocal Raman microscopy, differential scanning calorimetry, and X-ray diffraction). Long-term and accelerated stability tests were also performed, following ICH guidelines. Sterilization was achieved by exposing samples to gamma radiation. In vivo exploratory studies were carried out in healthy rabbits to evaluate the safety and overall performance of the implantable formulation. <b>Results</b>: In terms of quality control, drug content was found to be homogeneously distributed throughout the implants, and it also met the label claim. In vitro release rate was constant for MOX HCl, but non-linear for DEX, increasing over time. In vivo preliminary tests showed that the inserts completely biodegraded within approximately 20 days. No clinical signs of anterior segment toxic syndrome or statistically significant intraocular pressure differences were found between treatment and control groups. <b>Conclusions</b>: The implants developed in this study can act as sustained-release depots for the delivery of both DEX and MOX HCl, and are biocompatible with ocular structures.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177282","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":"Personalized Therapeutic Advances in Erythropoietin Signaling: From Anemia Management to Extensive Clinical Applications.","authors":"Elena-Christen Creangă, Raluca Stan, Alina-Crenguţa Nicolae, Cristina Manuela Drăgoi, Ion-Bogdan Dumitrescu","doi":"10.3390/pharmaceutics17091190","DOIUrl":"10.3390/pharmaceutics17091190","url":null,"abstract":"<p><p>Erythropoietin (EPO) is a glycoprotein hormone essential for red blood cell production and a cornerstone therapy for anemia, particularly in chronic kidney disease. Beyond hematopoiesis, EPO exerts pleiotropic effects on metabolism, neuroprotection, and tissue regeneration. This review summarizes current insights into the molecular mechanisms, pharmacokinetics, and clinical applications of recombinant human EPO (rHuEPO) and its analogs, with emphasis on personalized therapeutic strategies. Emerging evidence highlights both therapeutic opportunities and risks, including resistance, cardiovascular complications, and misuse in sports doping. Advances in detection methods, pharmacogenomics, and the development of novel agents such as HIF-prolyl hydroxylase inhibitors are discussed, underscoring the expanding role of EPO in precision medicine.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177316","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":"Development of pH-Sensitive Multiparticulates for Orally Disintegrating Tablets of Proton Pump Inhibitors: Physicochemical Characterization and Drug Release Studies.","authors":"Mahendra Singh, Punna Reddy Ullapu, Arokia Vijaya Anand Mariadoss, Satyender Kumar, Sung Gu Kang","doi":"10.3390/pharmaceutics17091187","DOIUrl":"10.3390/pharmaceutics17091187","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Enteric coating protects active pharmaceutical ingredients from gastric degradation, but conventional tablets may present swallowing difficulties in geriatric and pediatric patients. Hence, this study intended to develop pH-responsive multiparticulates, formulated into orally disintegrating tablets (ODTs), for targeted intestinal drug delivery in individuals with dysphagia. <b>Methods:</b> Multiparticulates were developed via sequential seal coating, drug layering, sub-coating, and enteric coating on inert cores using a fluidized bed coater (Pam Glatt, India; bottom spray). Selected enteric-coated batches were directly compressed into ODTs using microcrystalline cellulose (Avicel PH102) and mannitol (Pearlitol SD 160) as fillers, with Explotab^®, Ac-Di-Sol^®, or crospovidone M^® as superdisintegrants. <b>Results:</b> Multiparticulates exhibited mean diameters of 197.671-529.511 μm and span values of 0.603-0.838. Span value < 1, indicating a narrow size distribution. Electron microscopy confirmed the spherical morphology of Batches 7a and b. Enteric-coated batches (5b, 6, 7a, 7b) released ≤10% of the drug in 0.1 N HCl at 2 h. Optimized formulation ODT 7b released 7.904% of the drug under gastric conditions and 79.749% in phosphate buffer (pH 6.8) within 2.5 h, following first-order drug release kinetics. ODT 7b demonstrated hardness (2.538 ± 0.144 kg/cm²), wetting time (11.17 ± 1.051 s), friability (0.712%), and drug content (99.81 ± 1.01%) within acceptable limits. <b>Conclusions:</b> The pH-dependent multiparticulates provided sustained intestinal drug release and, when incorporated into ODTs, yielded a dosage form with a rapid wetting time and acceptable mechanical properties. This dosage form can offer a promising approach for improving compliance and therapeutic efficacy in patients with swallowing difficulties (dysphagia).</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177412","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":"Machine Learning for Multi-Target Drug Discovery: Challenges and Opportunities in Systems Pharmacology.","authors":"Xueyuan Bi, Yangyang Wang, Jihan Wang, Cuicui Liu","doi":"10.3390/pharmaceutics17091186","DOIUrl":"10.3390/pharmaceutics17091186","url":null,"abstract":"<p><p>Multi-target drug discovery has become an essential strategy for treating complex diseases involving multiple molecular pathways. Traditional single-target approaches often fall short in addressing the multifactorial nature of conditions such as cancer and neurodegenerative disorders. With the rise in large-scale biological data and algorithmic advances, machine learning (ML) has emerged as a powerful tool to accelerate and optimize multi-target drug development. This review presents a comprehensive overview of ML techniques, including advanced deep learning (DL) approaches like attention-based models, and highlights their application in multi-target prediction, from traditional supervised learning to modern graph-based and multi-task learning frameworks. We highlight real-world applications in oncology, central nervous system disorders, and drug repurposing, showcasing the translational potential of ML in systems pharmacology. Major challenges are discussed, such as data sparsity, lack of interpretability, limited generalizability, and integration into experimental workflows. We also address ethical and regulatory considerations surrounding model transparency, fairness, and reproducibility. Looking forward, we explore promising directions such as generative modeling, federated learning, and patient-specific therapy design. Together, these advances point toward a future of precision polypharmacology driven by biologically informed and interpretable ML models. This review aims to provide researchers and practitioners with a roadmap for leveraging ML in the development of safer and more effective multi-target therapeutics.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177539","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}