AAPS PharmSciTech最新文献

{"title":"Dual-Responsive Ion-Exchange Resin Encapsulated Atomoxetine Hydrochloride for Taste-Masking and Biphasic Release","authors":"Tao Xiao,&nbsp;Quanzhu Yang,&nbsp;Lusi Chen,&nbsp;Jiayu Xie,&nbsp;Huiying Zhong,&nbsp;Guoqing Zhang,&nbsp;Haibing He,&nbsp;Hongfei Liu","doi":"10.1208/s12249-025-03111-w","DOIUrl":"10.1208/s12249-025-03111-w","url":null,"abstract":"<div><p>Atomoxetine hydrochloride (ATH) is a first-line medication used to treat Attention Deficit Hyperactivity Disorder (ADHD) in children. However, it poses challenges such as a bitter taste and difficulties in dose adjustment. While once-daily administration may result in excessive drug exposure, twice-daily dosing improves plasma drug concentration stability but can reduce patient compliance, especially in school-aged children. To address these challenges, a novel strategy was proposed that involves encapsulating ATH into ion exchange resins (IERs) (referred to as ATH@IER). The pH-responsive release of ATH from the ATH@IER exhibited a limited release rate in neutral conditions, effectively masking the bitter taste, which was evaluated through electronic tongue analysis. The cation-responsive release of ATH from the ATH@IER demonstrated immediate-release (IR) property, which was combined with Eudragit^® RS100 coated ATH@IER (ATH@MC) to establish a biphasic release system. ATH orally disintegrating tablets (ATH ODT) were manufactured using a composition of ATH@IER and ATH@MC (40:60, w/w), along with other excipients. Pharmacokinetic studies demonstrated that a single dose of ATH ODT produced a bimodal plasma concentration, resulting in a two-fold decrease in peak concentration (C_max) while maintaining an unchanged area under the drug concentration–time curve (AUC_0-t) compared to the commercial ATH oral solution administered once. Notably, the plasma drug concentration of ATH ODT remained steadier than that of the commercial product when administered twice. In conclusion, ATH ODT represents a promising formulation that effectively masks bitter taste and provides biphasic release for the treatment of ADHD.</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":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888696","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":"Isotretinoin-Loaded Topical Lipid Liquid Crystal for the Treatment of Acne: In-Vitro and In-Vivo Evaluations","authors":"Armita Sedighidarijani,&nbsp;Shiva Golmohammadzadeh,&nbsp;Hossein Kamali,&nbsp;Bahman Khameneh,&nbsp;Elham Khodaverdi,&nbsp;Ali Nokhodchi","doi":"10.1208/s12249-025-03106-7","DOIUrl":"10.1208/s12249-025-03106-7","url":null,"abstract":"<div><p>Effective acne treatment is critical due to its profound impact on physical and psychological well-being. It was shown that severe systemic side effects, including teratogenicity, ovarian reserve reduction, depression, dry skin, hypertriglyceridemia, and intracranial hypertension limited oral isotretinoin usage. Therefore, this study addresses these challenges by developing isotretinoin-loaded lipid liquid crystal (LLC-IT) nanoparticles for topical application, aiming to enhance localized delivery while minimizing systemic exposure. LLC-IT nanoparticles were prepared using a top-down method and evaluated for their physicochemical properties, photostability, cytotoxicity, antimicrobial activity, <i>in-vitro</i> drug release, and <i>in-vivo</i> therapeutic efficacy. A testosterone-induced acne mouse model was used to compare LLC-IT treatment with untreated and commercial isotretinoin gel-treated groups. LLC-IT nanoparticles exhibited a uniform particle size (69.57 ± 0.51 nm), low polydispersity index (0.264 ± 0.01), and stable zeta potential (- 19.3 ± 0.2 mV). High encapsulation efficiency (95% ± 3) and effective loading capacity (1.15% ± 0.13) were achieved. Drug release was diffusion-controlled with minimal UV-induced degradation. Stability assessments over 12 months confirmed consistent properties across varying storage temperatures. LLC-IT displayed significant antibacterial activity and reduced skin irritation in Draize tests compared to commercial gels. <i>In-vivo</i>, LLC-IT reduced inflammation significantly more than untreated or commercial gel-treated groups, indicating enhanced therapeutic efficacy of LLC-IT formulation. The isotretinoin-loaded lipid liquid crystal formulation shows superior stability and efficacy with reduced side effects compared to conventional treatments, offering a more effective and patient-friendly solution, as well as a promising alternative for industrial production in acne management.</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":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03106-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888668","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":"Integration of Synchronizing In Silico, In Vitro, and In Vivo Strategies for the Development of Antipsoriatic Apremilast-loaded Nanostructured Lipid Carrier Embedded in Hydrogel","authors":"Nikita Patel,&nbsp;Aneri Desai,&nbsp;Bhavin Vyas,&nbsp;Pranav Shah,&nbsp;Mangrulkar Shubhada,&nbsp;Umekar Milind,&nbsp;Kamla Pathak,&nbsp;Mahavir Bhupal Chougule","doi":"10.1208/s12249-025-03103-w","DOIUrl":"10.1208/s12249-025-03103-w","url":null,"abstract":"<div><p>One of the major challenges in the psoriasis therapies is the systemic side effects. This research investigation intended to design, formulate, and characterize topical Apremilast (APR) nanostructured lipid carriers (NLCs) embedded hydrogel. APR-loaded NLCs were prepared using the hot melt ultrasonication technique using glyceryl monostearate (GMS) and Capmul^® MCM, followed by high-speed homogenization. The entrapment and size were 85.5 ± 2.1% and 242.5 ± 3.1 nm, respectively. Using molecular docking, the interactions between APR-GMS and APR-Capmul^® MCM were investigated. 3² factorial designs were used to optimize APR-loaded NLCs, employing a quality-by-design approach. The spherical shape of the nanocarriers was depicted in the SEM images of NLCs dispersion. With a regression value of 0.9745, the <i>in vitro</i> drug release of APR-NLCs dispersion matched the Higuchi model and demonstrated extended-release up to 28 hrs (99.0 ± 1.7%). An <i>in vitro</i> cellular toxicity depicted that formulation excipients had minimal effect, as cell viability was still &gt; 80% at concentrations of up to 30 µg/mL. APR-NLC hydrogel exhibited extended release up to 36 hrs (97.1 ± 0.8%), with diffusion as a release mechanism. Since there was no significant difference observed in viscosity (cp) or % CDR throughout 24 hrs at 5°, indicate APR-NLCs hydrogel was stable in a refrigerated condition. Compared to the positive control, APR liquid, and pure drug, APR-NLCs hydrogel showed a substantial decrease in PASI score. Topical APR-loaded NLCs embedded in Hydrogel enhanced efficacy in the imiquimod-induced psoriasis in the murine model found to be non-irritating with minimal systemic side effects. The findings imply that APR-loaded NLCs embedded in Hydrogel can be used topically to treat psoriasis by focusing on the skin's outer layers.</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":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875466","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":"Collagenase-functionalized Liposomes Based on Enhancing Penetration into the Extracellular Matrix Augment Therapeutic Effect on Idiopathic Pulmonary Fibrosis","authors":"Xiaoqing Liu,&nbsp;Xiaoling Dong,&nbsp;Zhen Peng,&nbsp;Cuihong Wang,&nbsp;Jianwei Wan,&nbsp;Min Chen,&nbsp;Chunli Zheng","doi":"10.1208/s12249-025-03112-9","DOIUrl":"10.1208/s12249-025-03112-9","url":null,"abstract":"<div><p>In this study, a quercetin-loaded liposome system modified with collagenase was developed to increase QU penetration in the ECM and improve IPF treatment. Quercetin-loaded long circulation liposome (QU-LP) and quercetin-loaded liposome modified with collagenase type I (QU-CLP) were prepared, followed by characterization of the encapsulation efficiency, particle size, morphology, and <i>in vitro</i> drug release. Their effect on the cytotoxicity of A549 cells was detected by the Cell Counting Kit-8, and the cellular uptake was investigated using cellular fluorescence imaging and flow cytometry. TGF-β1 induced A549 cell model was established to mimic pulmonary fibrosis to explore further the anti-pulmonary fibrosis effect of QU-CLP by CCK8 experiment. QU-CLP significantly improves the solubility and bioavailability of QU by encapsulating it in the internal cavity with a high encapsulation efficiency (EE%) of 92.86 ± 1.03%. Liposomes alleviate the influence of QU on normal A549 cell growth. Enhanced fluorescence intensity was observed in A549 cells treated with coumarin 6-labeled and collagenase-modified nanoliposomes (C6-CLP) after 4 h of incubation on the collagen matrix, confirming that collagenase-loaded liposomes could penetrate the collagen barrier and cells internalized more hydrophobic drug. The mean fluorescence intensity (MFI) of the C6-CLP group was 2.88 times that of the C6-labeled nanoliposomes (C6-LP). Moreover, QU-CLP significantly (**<i>P</i> &lt; 0.01) inhibited the proliferation of A549 cells stimulated by TGF-β1. QU-CLP has excellent potential for delivering QU with enhanced bioavailability, high cellular uptake efficiency, and improved therapeutic efficacy in IPF.</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":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875468","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":"Carboplatin Co-loaded 5-Fluorouracil Nanoparticles Conjugated with Trastuzumab for Targeted Therapy in HER2+ Heterogeneity Breast Cancer","authors":"Akshay Kumar Lunawat,&nbsp;Debanjan Mukherjee,&nbsp;Riya Shivgotra,&nbsp;Sarjana Raikwar,&nbsp;Ankit Awasthi,&nbsp;Amrinder Singh,&nbsp;Shamsher Singh,&nbsp;Shivani Chandel,&nbsp;Subheet Kumar Jain,&nbsp;Shubham Thakur","doi":"10.1208/s12249-025-03107-6","DOIUrl":"10.1208/s12249-025-03107-6","url":null,"abstract":"<div><p>Breast cancer, the second-most common cause of cancer-related deaths among women, remains a significant global health challenge. This study focuses on developing trastuzumab (TmAb)-functionalized chitosan nanoparticles (CS-NPs) co-loaded with carboplatin and 5-fluorouracil (5-FU) for targeted treatment of HER2-positive breast cancer. The NPs were prepared via the ionic gelation method, optimized using Design of Experimentation (DoE), and characterized for particle size, zeta potential, PDI, and entrapment efficiency. TmAb conjugation was achieved using NHS and EDC, and further characterization included TEM, syringeability, hemolytic toxicity, <i>in-vitro</i> release, <i>ex-vivo</i> cell line study, and <i>in-vivo</i> anti-cancer activity using the Ehrlich ascites carcinoma (EAC) model. The <i>in-vitro</i> release studies indicated enhanced drug release at pH 5.5 over 32 h and showed first-order kinetics. The TmAb-conjugated NPs demonstrated specificity and targeting in the SK-BR-3 cell line and significant anti-cancer activity in the EAC model, with the highest tumor inhibition rate of 85.19% compared to 58.12% for the drug solution. These findings highlight the potential of TmAb-conjugated NPs for targeted breast cancer therapy, offering improved drug delivery and therapeutic efficacy, paving the way for future clinical applications to reduce side effects and overcome the limitations of conventional chemotherapy.</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":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875467","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":"Proposals for Global Harmonization of Regulations for Testing of Spacers and Valved Holding Chambers for Pressurized Metered Dose Inhalers","authors":"Jolyon P. Mitchell","doi":"10.1208/s12249-025-03110-x","DOIUrl":"10.1208/s12249-025-03110-x","url":null,"abstract":"<div><p>Thought should be given to the desirability for similar approaches for the present transition to low global warming potential (LGWP) propellants for pressurized metered dose inhalers (pMDIs)  to be adopted by both European Medicines Agency (EMA) and the United States Food and Drug Administration  (FDA) for the performance testing of pMDIs that include the evaluation with an add-on spacer or valved holding chamber as part of the <i>in vitro</i> component for product registration. If such an add-on device was to be included as part of the registration package in either US or European regulatory environments, the content of United States Pharmacopeia (USP) chapter &lt;1602&gt; could support the process.</p></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143845659","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":"Nasal In-Situ Gels of Brij®-Enriched Novasomes as Optimistic Nanovesicular Carriers for Enhancing Anti-Depressant Action of Agomelatine","authors":"Tarek M. Ibrahim,&nbsp;Ayman M. Fathi,&nbsp;Nourhan A. Abdulla","doi":"10.1208/s12249-025-03097-5","DOIUrl":"10.1208/s12249-025-03097-5","url":null,"abstract":"<div><p>The purpose of study was to exploit distinctive features of nasal administration route to boost agomelatine permeation and upgrade its anti-depressant action after being embedded in Brij^®-enriched novasomes (NVs) as non-phospholipid vesicular systems. Different amounts and types of excipients were used to evaluate NVs using definitive screening design (DSD). Optimal NV was incorporated in thermosensitive <i>in-situ</i> gels containing poloxamer 407 (P-407) and hydroxypropyl methyl cellulose (HPMC). After evaluation of novasomal <i>in-situ</i> gels (NVGs), optimal NVG was subjected to <i>ex-vivo</i>, <i>in-vivo</i>, and biochemical investigations. Results showed significant increase in entrapment capability (EC%), particle size (P.S), and zeta potential (Z.P) of NVs after increasing free fatty acid, surfactant, and cholesterol amounts. The capability of Brij^® to improve fluidization of lipid bilayers, decrease P.S, and increase Z.P was observed. Lipohilicity, EC%, and Z.P of Brij^® 56-enriched NVs were higher than those containing Brij^® 35. Gradual increase in HPMC concentration and gel/NV ratio led to marked decrease in gelation time and spreadability and increase in gel strength and viscosity values of NVGs. Optimal NVG9 displayed higher permeation profile (538.34 μg/cm²) and drug flux (39.38 μg/cm².h⁻¹) through fresh sheep nasal mucosa in comparison to control gel (150.76 μg/cm² and 14.44 μg/cm².h⁻¹, respectively). Rats treated with nasal optimal NVG9 manifested increased sucrose preference (SP) percent (80.73%) and levels of dopamine (50.42 ng/g) and serotonin (44.92 ng/g) with decreased low latency time values (5.86 min). This study confirmed the <i>in-vivo</i> safety and amplification of precognitive and anti-depressant action of agomelatine after intranasal administration.</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":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03097-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143845660","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":"Formononetin-Loaded PLGA Large Porous Microparticles via Intratracheal Instillation for Bleomycin-Induced Pulmonary Fibrosis Treatment","authors":"Hongting Liu,&nbsp;Yao Sun,&nbsp;Shihao Cai,&nbsp;Conglu Zhao,&nbsp;Xiang xu,&nbsp;Aiguo Xu,&nbsp;Honggang Zhou,&nbsp;Cheng Yang,&nbsp;Xiaoting Gu,&nbsp;Xiaoyu Ai","doi":"10.1208/s12249-025-03089-5","DOIUrl":"10.1208/s12249-025-03089-5","url":null,"abstract":"<div><p>Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease of unknown cause, with few effective therapies available and high mortality rates. Our preceding research indicated that formononetin (FMN) could improve the symptoms of the bleomycin-induced pulmonary fibrosis and be a promising drug against IPF. In this study, an inhalable formononetin-loaded poly(lactic-co-glycolic) acid (PLGA) large porous microspheres (FMN-PLGA-MSs) was prepared by the method of emulsion solvent evaporation. SEM showed that FMN-PLGA-MSs were loose particles existing many pores on the surfaces, and the measured mean geometric diameter was more than 10 µm. The encapsulation efficiency (EE) and drug loading efficiency (DL) were 87.72 ± 6.34% and 4.18 ± 0.30%. FMN in FMN-PLGA-MSs could be rapidly released within 2 h and sustainably released for 21 d. Cell tests and q-RT-PCR tests showed that FMN could inhibit the activation of fibroblasts and the deposition of extracellular matrix (ECM) by acting on the TGF-β1/Smad3 signaling pathway. FMN-PLGA-MSs showed higher antifibrotic effects than free FMN oral administration in the pulmonary fibrosis models of mice, remarkably improving pulmonary function, decreasing hydroxyproline levels, and attenuating lung injuries. By formulating formononetin into microsphere preparations, its solubility can be significantly enhanced, enabling effective pulmonary drug delivery. This approach not only improves lung targeting but also reduces systemic toxicity. Additionally, it facilitates superior lung deposition and extends the retention time of the formononetin within the lungs. Taken together, FMN-PLGA-MSs may be a promising inhaled medication for the treatment of IPF.</p><h3>Graphical Abstract</h3><p>Formononetin (FMN) can improve the symptoms of idiopathic pulmonary fibrosis (IPF). Large porous microparticle can improve lung retention and lung targeting. FMN is loaded in poly(lactic-co-glycolic)acid (PLGA) to get microspheres (FMN-PLGA-MSs) for intratracheal instillation treatment of IPF. FMN-PLGA-MSs remarkably improved pulmonary function, decreased hydroxyproline, and attenuated lung injuries. FMN-PLGA-MSs are promising intratracheal instillation medication for the treatment of IPF.\u0000</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143845662","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":"Chitosan Nanoparticles: Approaches to Preparation, Key Properties, Drug Delivery Systems, and Developments in Therapeutic Efficacy","authors":"Wasfy M. Obeidat,&nbsp;Ishraq K. Lahlouh","doi":"10.1208/s12249-025-03100-z","DOIUrl":"10.1208/s12249-025-03100-z","url":null,"abstract":"<div><p>The integration of nanotechnology into drug delivery systems holds great promise for enhancing pharmaceutical effectiveness. This approach enables precise targeting, controlled release, improved patient compliance, reduced side effects, and increased bioavailability. Nanoparticles are vital for transporting biomolecules—such as proteins, enzymes, genes, and vaccines—through various administration routes, including oral, intranasal, vaginal, buccal, and pulmonary. Among biodegradable polymers, chitosan, a linear polysaccharide derived from chitin, stands out due to its biocompatibility, safety, biodegradability, mucoadhesive properties, and ability to enhance permeation. Its cationic nature supports strong molecular interactions and provides antimicrobial, anti-inflammatory, and hemostatic benefits. However, its solubility, influenced by pH and ionic sensitivity, poses challenges requiring effective solutions. This review explores chitosan, its modified derivatives and chitosan nanoparticles mainly, focusing on nanoparticles physicochemical properties, drug release mechanisms, preparation methods, and factors affecting their mean hydrodynamic diameter (particle size). It highlights their application in drug delivery systems and disease treatments across various routes. Key considerations include drug loading capacity, zeta potential, and stability, alongside the impact of molecular weight, degree of deacetylation, and drug solubility on nanoparticle properties. Recent advancements and studies underscore chitosan's potential, emphasizing its modified derivatives'versatility in improving therapeutic 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":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143845605","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":"The Amorphous State of the Antiepileptic Clobazam: Preparation and Characterization","authors":"Marina M. Marcos Valdez,&nbsp;Julio Sanchez,&nbsp;María E. Bertotto,&nbsp;Octavio E. Fandiño,&nbsp;Fernando P. Cometto,&nbsp;Norma R. Sperandeo","doi":"10.1208/s12249-025-03101-y","DOIUrl":"10.1208/s12249-025-03101-y","url":null,"abstract":"<div><p>The aim of this study was to prepare and characterize amorphous clobazam (CLOB) and investigate its devitrification under various stressors (temperature/humidity, compaction and mechanical/thermal stresses). Amorphous CLOB was prepared by melt-quenching in liquid nitrogen. The quench-cooled sample (CLOB-q) was characterized via polarized light and hot-stage microscopies (PLM and HSM), X-ray powder diffraction (XRPD), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), conventional and modulated DSC (DSC-c and MDSC®), thermogravimetry (TG), dynamic mechanical analysis (DMA), X-ray photoelectron spectroscopy (XPS) and contact angle measurements. Stability of CLOB-q toward temperature/humidity, compaction, and combined mechanical and thermal stress were also evaluated. CLOB-q was a truly amorphous form, as revealed by DSC-c, MDSC® and DMA. Its calorimetric glass transition temperature (Tg) was 67.0 °C (20 °C/min) and the ratio Tm/Tg was 1.34, indicating a fragile glass. The water contact angle of CLOB-q (121.8° ± 1.7°) was lower than that of crystalline CLOB (CLOB-c, 131.3° ± 3.6°), likely due to its higher concentration of surface CL, as determined by XPS. Storage of CLOB-q at - 20 °C/0% RH, 25 °C/0% RH and 40 °C/75% RH resulted in its complete devitrification to CLOB-c within 60 days, 4 days, and 42 h respectively. Subjection of CLOB-q to compaction (19.6 kN) and combined mechanical-thermal stresses also resulted in complete crystallization to CLOB-c. In conclusion, amorphous CLOB was successfully prepared in the laboratory for the first time and thoroughly characterized. It easily devitrified to CLOB-c by effect of different stressors, and thus it could not have advantages over CLOB-c in terms of physical stability.</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":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143845606","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}