AAPS PharmSciTech最新文献

{"title":"Degradable Hydrogel Microspheres for Drug Delivery: In Vitro Performance and Influence of E-Beam Sterilization.","authors":"Laurent Bédouet, Anne Beilvert, Emeline Servais, Laurence Moine","doi":"10.1208/s12249-025-03144-1","DOIUrl":"https://doi.org/10.1208/s12249-025-03144-1","url":null,"abstract":"<p><p>The present work examines the in vitro drug delivery performance of degradable microspheres (DrugMic) composed of a crosslinked hydrogel of poly(ethylene glycol), with particular interest on the effect of e-beam sterilization on the stability of loaded active substances, i.e. niflumic acid (14% w/w), tadalafil (7% w/w), travoprost (0.2% w/w), buprenorphine (1.4% w/w), teicoplanin (6% w/w), and polymyxin B (5.6% w/w). Drug loading was performed on preformed microspheres degradable in 3 days, 1 or 2 weeks. Drugs were loaded onto microspheres (50-100 µm or 500-700 µm) via 1 h room-temperature incubation. After freeze-drying, drug-loaded microspheres were sterilized using e-beam irradiation (15 or 25 kGy). In vitro drug releases were done in PBS, drug elution profiles and radiostability were assessed by RP-HPLC with diode array detection. Following irradiation, DrugMic delivered niflumic acid and tadalafil for 3 days, teicoplanin and polymyxin B for 1 week, buprenorphine and travoprost for 2 weeks from microspheres degradable in 3 days, 1 and 2 weeks. Radiolysis was observed in each fraction collected during buprenorphine (0.7-20%) and travoprost (1.8-139%) release, while the HPLC profiles of polymyxin B were completely altered, indicating substantial degradation. Niflumic acid, tadalafil and teicoplanin showed no signs of radiolysis. Extemporaneous loading of buprenorphine and polymyxin B onto sterilized microspheres was attempted to avoid radiolysis. The sustained release profiles were maintained without degrading the drug. DrugMic appears to be a suitable platform for sustained drug release. The loading mode can be adapted according to the stability of the drug to irradiation.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":"162"},"PeriodicalIF":3.4,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144223926","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":"Advances in Characterization of Transdermal and Topical Products using Texture Analyzer Systems.","authors":"Khadeejeh Al-Smadi, Masood Ali, Jiexin Zhu, Ayyah Abdoh, Khanh Phan, Yousuf Mohammed","doi":"10.1208/s12249-025-03148-x","DOIUrl":"https://doi.org/10.1208/s12249-025-03148-x","url":null,"abstract":"<p><p>The efficacy, safety, and stability of transdermal and topical products (TTPs) are of prime importance to consumer acceptance and compliance. To control the consistent textural quality or overall physical properties of TTPs, texture analysis tests are widely applied to assess potential changes in features and internal structure of products throughout different stages of formulation development, manufacturing, and distribution. As one of the essential texture test types, Texture Profile Analysis (TPA) provides critical insights into the structure, spreadability, adhesion, sensory attributes, and consistency of semisolid formulations via key measured parameters such as hardness, adhesiveness, cohesiveness, elasticity, and compressibility. Recent advancements in automation and multimodal analysis have enhanced the precision and applicability of TPA. For transdermal delivery systems (TDS), adhesion, a critical quality attribute (CQA), which is influenced by viscoelasticity, surface energy, and wetting characteristics of pressure-sensitive adhesives (PSAs), can be assessed through in vitro methods like peel, tack, and shear tests using texture analyzer systems. While in vivo assessments remain subjective, in vitro tests conducted by texture analyzers enable standardized and reproducible evaluations, ensuring reliable comparisons across products and bridging gaps between laboratory and real-world performance. Microneedles (µNDs), another innovative transdermal platform, require robust mechanical strength to ensure effective skin penetration and drug release. Texture analysis plays a pivotal role in characterizing critical properties such as hardness, flexibility, and puncture strength, simulating forces encountered during skin penetration. This analysis offers valuable insights into µND performance, ensuring safety, functionality, and patient compliance. This review systematically curates existing knowledge on using texture analyzers to measure textural properties of pharmaceutical TTPs while highlighting emerging trends and providing methodologies for testing and parameter derivation. By emphasizing the importance of CQA characterization for novel drug delivery platforms, this work underscores the role of texture analysis in optimizing designs of TTPs including µND, focusing on fracture, insertion, and bending forces, ultimately contributing to the development of safer and more efficient transdermal systems.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":"157"},"PeriodicalIF":3.4,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214518","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":"Sublingual Delivery of Human GLP-1 Loaded Nanoliposomal Hydrogel for Treatment of Type 2 Diabetes Mellitus.","authors":"Shivani Khopade, Tejas Girish Agnihotri, Shraddha Baviskar, Bhaskar Pavar, Shyam Sudhakar Gomte, Tejas Maskar, Nitish Sharma, Hemant Kumar, Santosh Kumar Behera, Aakanchha Jain","doi":"10.1208/s12249-025-03152-1","DOIUrl":"https://doi.org/10.1208/s12249-025-03152-1","url":null,"abstract":"<p><p>Type-2 diabetes mellitus (T2DM) is a chronic metabolic condition with more than 95% of the cases worldwide and can cause complications like retinopathy, nephropathy, cardiovascular problems, etc. Currently, major treatment protocols available for T2DM include oral hypoglycemic agents, insulin, and GLP-1 receptor agonists. Due to the unique mechanism of action, human glucagon-like peptide-1 (HuGLP-1) has been a focus for management of T2DM. Oral HuGLP-1 delivery is hindered by its hydrophilic nature, preventing intestinal absorption. Additionally, the unfavorable gut environment and hepatic metabolism significantly restrict its bioavailability. Sublingual administration offers a potential solution bypassing these obstacles. This route avoids first-pass metabolism and prevents enzymatic exposure of peptide thus enhancing its absorption. The goal of the present work is to design HuGLP-1 loaded hydrogel embedded with nanoliposomes that would protect it from systemic enzymes and extend the duration it spends in the bloodstream, improving its pharmacological activity. The particle size, polydispersity index, and entrapment efficiency of optimized HuGLP-1-NLs were found to be 179.2 ± 1.65 nm, 0.167 ± 0.01, and 47 ± 2.18%, respectively. Post sublingual delivery of HuGLP-1 NLs loaded hydrogel in T2DM induced SD rats, it showed significantly less reversal of hypoglycemia than the standard hydrogel (p < 0.001). In summary, extended sublingual administration of this formulation could boost T2DM management by improving patient compliance. This formulation could also be used for managing diabetes-related obesity and needs to be validated by preclinical testing on a large number of animal models.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":"155"},"PeriodicalIF":3.4,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214523","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":"Nanocarrier-based Drug Delivery Systems to Enhance Antimicrobial Photodynamic Therapy in Dental Applications: A Review.","authors":"Negar Ebrahimi, Alireza Ranjbar, Sima Shahabi, Shima Afrasiabi","doi":"10.1208/s12249-025-03155-y","DOIUrl":"https://doi.org/10.1208/s12249-025-03155-y","url":null,"abstract":"<p><p>Antimicrobial resistance and oral dysbiosis often reduce the efficacy of conventional antimicrobial treatments. In addition, poor permeability and insufficient accumulation of therapeutic agents in biofilms are the main causes of failure in the treatment of oral infections. Antimicrobial photodynamic therapy (PDT) is a versatile therapeutic approach that uses light-activated photosensitizers to fight bacterial infections. When irradiated with light of a specific wavelength, photosensitizers generate reactive oxygen species that selectively damage microbial cells. However, most photosensitizers are poorly soluble in water, which limits their clinical application. Nanotechnology offers a promising solution by incorporating nanocarriers into PDT. Nanocarriers can play a crucial role in improving PDT by overcoming the limitations of conventional photosensitizers. They can encapsulate photosensitizers, protect them from premature degradation, and improve their penetration and delivery to target sites. In this review, different drug delivery systems based on nanocarriers are investigated to improve the efficacy of PDT in dental applications.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":"160"},"PeriodicalIF":3.4,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214520","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":"Freeze-Drying as a Tool for Preparing Porous Materials: From Proof of Concept to Recent Pharmaceutical Applications.","authors":"Kawthar K Abla, Mohammed M Mehanna","doi":"10.1208/s12249-025-03117-4","DOIUrl":"https://doi.org/10.1208/s12249-025-03117-4","url":null,"abstract":"<p><p>Freeze-drying (FD) is the most extensive drying technique in pharmaceutical and biopharmaceutical industries. It relies on three main steps: freezing, primary, and secondary drying, where the sample is frozen and then dried by ice sublimation. FD possesses several features, mainly its suitability for heat-sensitive materials and its ability to produce dry products with improved physicochemical characteristics. Although FD is a gentle drying process, it can cause numerous stresses that induce chemical and physical instabilities. Herein, the addition of suitable excipients along with optimizing the process parameters is critical in attaining lyophilizates with high-quality attributes. Besides, the freeze-drying method has been explored as a unique route to produce porous materials with different applications. This work aims to dismantle the basics of freeze-drying and its role in developing porous materials, mainly amorphous and co-amorphous solid-dispersions, orodispersible tablets and films, as well as porous dressings and 3D scaffolds for effective wound healing and tissue engineering, respectively. The challenges and limitations of lyophilization have also been addressed.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":"159"},"PeriodicalIF":3.4,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214519","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":"Preparation and Characterization of Diclofenac Sodium-Purolite A430MR Complexes for Taste Masking.","authors":"Genyang Ye, Qun Wang, Yibo Shang, Yibo Li, Rui Yang, Boyu Jing, Qiang Fu","doi":"10.1208/s12249-025-03138-z","DOIUrl":"https://doi.org/10.1208/s12249-025-03138-z","url":null,"abstract":"<p><p>The taste of a drug impacts the compliance of patients for oral administration. In this study, the bitter taste of diclofenac sodium (DS) was masked with purolite A430MR through ion exchange. The DS-A430MR complexes (DACs) were prepared at a 1:1 (w/w) drug to resin through a simple aqueous binding process. The key factors affecting release behaviors were identified by optimized experiments. The taste masking effect of the DACs was evaluated by human taste panel studies and simulated saliva release. The physical characterization proved successful preparation of DACs. The released experiments demonstrated that the pH values, types, and strengths of counter ions were important factors affecting the DS release from the DACs. The simulated saliva release profiles demonstrated that the DS concentration in oral cavity was lower than its bitterness threshold. The bitter taste of DS was almost completely masked by the IERs, which provided guidance for the development of palatable oral preparations using IERs.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":"158"},"PeriodicalIF":3.4,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advances in Development of Buccal Formulations: From Small to Macromolecules.","authors":"Vrundakumari R Solanki, Vijaykumar K Parmar","doi":"10.1208/s12249-025-03154-z","DOIUrl":"10.1208/s12249-025-03154-z","url":null,"abstract":"<p><p>Buccal drug delivery offers a promising alternative to conventional oral administration, bypassing hepatic first-pass metabolism and gastric degradation that often limit drug bioavailability. This review explores the anatomical and physiological characteristics of the buccal mucosa that make it amenable to drug absorption, examining key formulation strategies including Quality by Design (QbD) principles, the use of mucoadhesive polymers, and permeation enhancers. The review further highlights recent advancements in buccal drug delivery systems, with a particular focus on nanotechnology-based approaches for enhancing the delivery of small as well as macromolecules and biologics. A comprehensive literature analysis demonstrates the potential of buccal delivery to improve therapeutic outcomes by leveraging the unique properties of the buccal mucosa and optimizing drug absorption through advanced formulation design and innovative technologies.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":"156"},"PeriodicalIF":3.4,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214522","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 Role of Low Global Warming Potential Propellants on Suspension Metered Dose Inhaler Sprays.","authors":"Daniel J Duke, Lingzhe Rao, Benjamin Myatt, Phil Cocks, Stephen Stein, Hui Xin Ong, Paul Young","doi":"10.1208/s12249-025-03147-y","DOIUrl":"https://doi.org/10.1208/s12249-025-03147-y","url":null,"abstract":"<p><p>The reformulation of suspension-based pressurized metered dose inhalers (pMDI) with low global warming potential (GWP) propellants is challenged by wide-ranging changes to their chemicophysical properties such as vapor pressure, density and latent heat. The effect of low-GWP propellants on spray pattern and plume geometry for suspension pMDIs are not fully understood. There is a lack of data regarding the role of propellant choice and potential interactions with suspended drugs, which may explain performance variations between products and guide development of in-silico models. In this study, high speed imaging was used to measure the plume morphology and optical density of sprays containing HFA134a, HFA152a and HFO1234ze(E) propellants. Propellant-only placebo controls were compared to suspension formulations containing 2 mg/mL salbutamol sulphate. It was found that the presence of suspended particles has a significant effect on plume structure, reducing correlations between propellant thermophysical properties and cone angle, targeting angle, and optical center of mass by 6-7 times. These effects vary depending on propellant type due to variations in flash-evaporation behavior, which is less pronounced in low-GWP propellants compared to HFA134a. HFA152a sprays have a 23% reduction in Jakob number compared to HFA134a; plume width at the mouthpiece exit is commensurately increased by 40%. Equivalent HFO1234ze(E) sprays have less pronounced differences in Jakob number (13% reduced) and plume width (25% increased) compared to equivalent HFA134a sprays. Empirical models and standards which implicitly incorporate the flash-evaporation effects commonly observed in high-GWP HFA propellants may require adjustment to be suitable for use with low-GWP formulations.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":"154"},"PeriodicalIF":3.4,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207346","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":"Injectable PLGA-based In Situ Forming Subconjunctival Implant for Sustained Ocular Delivery of Ketotifen Fumarate: Formulation, Drug Release, and Biocompatibility Studies.","authors":"Nur Mita, Xuejia Kang, Pengyu Chen, Oladiran Fasina, Shenise Howard, Anna-Catherine Bowden, Richard J McMullen, Amol Suryawanshi, R Jayachandra Babu","doi":"10.1208/s12249-025-03142-3","DOIUrl":"https://doi.org/10.1208/s12249-025-03142-3","url":null,"abstract":"<p><p>Ketotifen fumarate is very effective in treating ocular conditions like allergic conjunctivitis. However, its clinical effectiveness is limited by rapid washout, frequent dosing, and poor bioavailability. This study developed a ketotifen fumarate-loaded in situ forming subconjunctival injectable implant (ISFSI) for use in large animal species such as horses and alpacas. ISFSIs were formulated by dispersing ketotifen fumarate in polylactide-co-glycolide (PLGA) combined with different release retarders (Kolliphor^® RH 40, Labrasol^®, and Maisine^®), then characterized for visual appearance, viscosity, solidification time, and in vitro drug release. The changes in the release medium pH and the solidified ISFSI wet weight were monitored for up to 4 weeks. The selected ISFSI, KFM5, was further characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and rheological behavior. The injectability of KFM5 was predicted using the power law for five different syringe and needle dimensions. Cytotoxicity was tested using the Alamar Blue assay and Calcein AM/PI staining on a human corneal epithelial cell line (HCE-T). Results showed that all ISFSI formulations were clear yellowish, with drug recoveries exceeding 95%, varying viscosities, and solidified upon contact with the release medium. KFM5 exhibited a triphasic drug release profile with the lowest burst release (4.91 ± 0.55%) and followed Higuchi kinetics. SEM imaging revealed a \"hollow and sponge-like\" structure, while DSC confirmed the crystallinity and thermal transitions of ketotifen fumarate within the solidified implant. Rheological analysis indicated shear-thinning fluid behavior with acceptable injection forces. Cytotoxicity assays confirmed > 90% cell viability, confirming biocompatibility in the ocular tissue.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":"153"},"PeriodicalIF":3.4,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207345","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":"Antitumor Efficacy of Paclitaxel Injection Concentrate for Nanodispersion in Patient-Derived Breast, Head and Neck, and Non-Small Cell Lung Cancer Mouse Xenografts.","authors":"Ajay J Khopade, Malay D Shah, Bhushan S Borole, Vinod Burade","doi":"10.1208/s12249-025-03153-0","DOIUrl":"https://doi.org/10.1208/s12249-025-03153-0","url":null,"abstract":"<p><p>Paclitaxel Injection Concentrate for Injection (PICN) is a novel nanoparticle formulation designed to overcome the limitations associated with the administration of marketed Cremophor and albumin based (nab) paclitaxel formulations. This study compared the in vivo antitumor efficacy of PICN with that of solvent-based paclitaxel and nab-paclitaxel in a murine NMRI nu/nu athymic nude mouse model bearing various human tumor xenotransplants: head and neck cancer (HNXF 1838 and HNXF 1842), lung cancer xenografts (LXFA 1584), and breast cancer xenografts (MAXF 574 and MAXF 1384). PICN displayed good to excellent antitumor activity. Moreover, PICN inhibited tumor growth more than solvent based paclitaxel formulation when compared at comparable tolerated dose levels. The higher antitumor efficacy of PICN compared to paclitaxel at lower dose levels of half the maximum tolerated dose (1/2MTD) was significant (P < 0.05) in three of the tumor models, i.e. HNXF 1842, MAXF 574, and MAXF 1384. The higher efficacy of PICN compared to paclitaxel was also evident at the MTD, but somewhat less pronounced, and was significant (P < 0.05) in one tumor model (HNXF 1838). The antitumor activity of PICN was similar to that of nab-paclitaxel. However, in one tumor model (HNXF 1838) PICN 50 mg/kg (1/2 MTD) showed a slight benefit over the same dose of nab-paclitaxel. The nanoparticulate nature of PICN and nab-paclitaxel therefore seems to enhance tumor cell penetration compared to conventional paclitaxel, resulting in better antitumor efficacy.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":"150"},"PeriodicalIF":3.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186233","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}