AAPS PharmSciTech最新文献

{"title":"Use of Benzene-Free Carbomer 980 in the Formulation of Metronidazole Gel 0.75% and Demonstration of Equivalence with Carbomer 940","authors":"Om Sambhaji Shelke,&nbsp;Jie Feng,&nbsp;Zhong Liu,&nbsp;Yulan Chen,&nbsp;Yijie Zhu,&nbsp;Zheng Zhang","doi":"10.1208/s12249-026-03487-3","DOIUrl":"10.1208/s12249-026-03487-3","url":null,"abstract":"<div><p>The U.S. FDA currently recommends avoiding carbomer grades that contain benzene and recommends benzene-free alternatives (USFDA. Guidance for Industry: reformulating drug products that contain carbomers manufactured with benzene. Center for Drug Evaluation and Research (CDER), Pharmaceutical Quality/CMC. Published in December 2023. Available at: https://www.fda.gov/media/175083/download). This means that if a finished product is authorized with a carbomer grade containing benzene, it needs to be replaced with a non-benzene carbomer grade. Such an update would also require detailed comparative studies—covering structure, performance, stability, and biological equivalence—to confirm consistent product quality and effectiveness. The current study attempted to replace Carbomer 940 (C940) with Carbomer 980 (C980) in 0.75% Metronidazole Gel. The two carbomer grades were characterized as powders using multiple spectroscopic techniques. A method for analyzing carboxylic acid content was developed and validated, using light-scattering resonance technology to improve accuracy. The formulation prepared with C940 and C980 was characterized for rheology, <i>in vitro</i> release and permeation, and stability, along with the reference formulation. Powder characterization shows slight differences in the absorption spectra across NMR and FTIR studies, while NIR spectra are the same. Additionally, C980 has a slightly higher molecular weight, degree of polymerization, apparent viscosity, and carboxylic acid content, but a lower water loss. The formulations prepared with C940 and C980 are rheologically equivalent to the reference formulation as assessed by flow curves, yield stress, linear viscoelasticity, and creep. The <i>in vitro</i> release and permeation study also demonstrates that the formulations prepared with C940 and C980 exhibit performance equivalence to the innovator formulation under the tested conditions. Hence, replacing the benzene-grade carbomer with the corresponding non-benzene-grade carbomer does not significantly affect product performance relative to the reference product.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148710917","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":"Retraction Note: 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/s12249-026-03501-8","DOIUrl":"10.1208/s12249-026-03501-8","url":null,"abstract":"","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-026-03501-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148552984","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":"Retraction Note: Bi-polymeric Spongy Matrices Through Cross-linking Polymerization: Synthesized and Evaluated for Solubility Enhancement of Acyclovir","authors":"Saima Asghar,&nbsp;Naveed Akhtar,&nbsp;Muhammad Usman Minhas,&nbsp;Kifayat Ullah Khan","doi":"10.1208/s12249-026-03497-1","DOIUrl":"10.1208/s12249-026-03497-1","url":null,"abstract":"","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148434742","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":"Correction: Scrutinizing the Feasibility of Nonionic Surfactants to Form Isotropic Bicelles of Curcumin: a Potential Antiviral Candidate Against COVID-19","authors":"Dina B. Mahmoud,&nbsp;Mohamed Mofreh Bakr,&nbsp;Ahmed A. Al-karmalawy,&nbsp;Yassmin Moatasim,&nbsp;Ahmed El Taweel,&nbsp;Ahmed Mostafa","doi":"10.1208/s12249-026-03470-y","DOIUrl":"10.1208/s12249-026-03470-y","url":null,"abstract":"","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-026-03470-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148417710","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":"The Role of Contract Manufacturing in Antibody–Drug Conjugate (ADC) Drug Substance Development – Strategies for Successful Engagement","authors":"Conor S. Barry","doi":"10.1208/s12249-026-03466-8","DOIUrl":"10.1208/s12249-026-03466-8","url":null,"abstract":"<div><p>Antibody–Drug Conjugates (ADCs) represent a rapidly evolving, and increasingly important frontier in targeted therapeutics, demanding specialised approaches to development and manufacturing. With a highly complex supply chain, specialist Contract Development and Manufacturing Organisations (CDMOs) play a critical role in ADC development. Increasingly, positive CDMO partnerships with sponsor companies can build competitive advantage in an increasingly innovative and competitive clinical development environment for ADCs. Carefully considered CDMO engagement strategies can be employed to deliver successful outcomes for ADC development and manufacture across the full spectrum of the development life-cycle. This commentary considers early and late-stage ADC development, focusing on the systematic optimisation, technology transfer, and gap analysis essential for robust scale-up and manufacture. Facility design requirements and process modifications are discussed in the context of scalable, cGMP-compliant manufacturing, highlighting the engineering and environmental controls necessary for the safe and efficient handling of ADCs. The discussion will offers insights into the requirements for successful ADC development and manufacture with CDMO partners, while ensuring, regulatory compliance.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-026-03466-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148417797","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":"A Review on Nanocarrier-Based Strategies for Sunitinib Delivery: Advances in Pharmacokinetic Enhancement and Targeted Theranostics","authors":"Mahesha Keerikkadu,&nbsp;Akshay Shetty,&nbsp;Raagul Seenivasan,&nbsp;Praveen Halagali,&nbsp;Vamshi Krishna Tippavajhala,&nbsp;Mahalaxmi Rathnanand","doi":"10.1208/s12249-026-03493-5","DOIUrl":"10.1208/s12249-026-03493-5","url":null,"abstract":"<div><p>Sunitinib malate (SNB) is a multitargeted tyrosine kinase inhibitor that inhibits tumor angiogenesis and proliferation by blocking signaling through VEGFR, PDGFR, c-KIT, FLT3, and RET. SNB is currently used in the treatment of renal cell carcinoma, gastrointestinal stromal tumors, and pancreatic neuroendocrine tumors. The pharmacological efficacy of SNB is limited by its poor aqueous solubility, pH-dependent dissolution, poor oral bioavailability, extensive first pass metabolism, high interpatient pharmacokinetic variability, and dose-limiting toxicities such as cardiotoxicity, hypertension, and myelosuppression. Nanotechnology-based drug delivery systems have been explored as a promising strategy to overcome the limitations and improve the pharmacological efficacy of SNB. A wide variety of SNB-loaded nanocarriers, including polymeric nanoparticles, lipid-based nanocarriers, nanocapsules, polymeric micelles, dendrimers, and inorganic nanostructures, have been developed to improve solubilization, protect the drug from degradation, and provide controlled or stimulus-responsive release. These nanocarriers provide improved pharmacokinetic properties by prolonging systemic circulation, increasing tumor accumulation through enhanced permeability and retention effects, and reducing off-target exposure. Active targeting and intracellular delivery mechanisms further enhance cellular uptake and pharmacological efficacy while reducing systemic toxicity. In addition, multifunctional nanocarriers that incorporate imaging agents or microenvironment-responsive components also offer opportunities for theranostic and precision oncology applications. However, clinical adoption is currently hindered by challenges associated with large-scale nanomanufacturing, batch-to-batch reproducibility, long-term nanostability, regulatory acceptance, and limited human data. This review critically evaluates current nanocarrier platforms for SNB delivery, provides pharmacological advancements achieved through nanoformulation, and identifies key translational hurdles and future directions for clinical adoption.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-026-03493-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403305","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":"A Review on Modular Peptide Anchoring Strategies for Functionalizing Liposomal Nanocarriers: Advancing Non-covalent Design Toward Targeted Cancer Therapy","authors":"Adamu Safiyanu Maikifi,&nbsp;Veerakiet Boonkanokwong","doi":"10.1208/s12249-026-03488-2","DOIUrl":"10.1208/s12249-026-03488-2","url":null,"abstract":"<div><p>Targeted drug delivery systems play a crucial role in improving the effectiveness and precision of cancer treatments. Liposomes have been widely investigated as drug carriers due to their versatility. Traditional methods for functionalizing liposomes involve covalent bonding of targeting ligands, which, while effective, can be complex and may affect the activity of the ligands. In contrast, non-covalent peptide insertion offers a simpler, more adaptable approach for incorporating targeting peptides into liposomal membranes using mechanisms such as hydrophobic interactions and electrostatic forces. This review examines non-covalent peptide-liposome interactions as the primary focus. We analyze mechanisms, incorporation techniques, and therapeutic applications with emphasis on formulation-relevant criteria including stability, manufacturability, and clinical translation. Critical evaluation of comparative advantages and limitations of each strategy provides decision frameworks for formulation scientists. We also address manufacturing challenges, quality control strategies, and regulatory considerations that influence clinical translation.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403299","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":"Hot-Melt Extrusion of Bupropion with Three Ethylcellulose Grades for Pellet Feedstock Preparation and Screw-Based 3D Printing of Sustained-Release Tablets","authors":"Chrystalla Protopapa,&nbsp;Laura Andrade Junqueira,&nbsp;Siva Satyanarayana Kolipaka,&nbsp;Sophia Economidou,&nbsp;Dimitris Pappas,&nbsp;Dennis Douroumis,&nbsp;Marilena Vlachou","doi":"10.1208/s12249-026-03494-4","DOIUrl":"10.1208/s12249-026-03494-4","url":null,"abstract":"<div><p>3D printing has emerged as a novel technology for producing personalized dosage forms tailored to patients’ therapeutic needs. Hot-melt extrusion (HME) is commonly used to produce filaments for most extrusion-based 3D printers. This study aimed to investigate the effect of three different ethylcellulose (EC) grades (7N, 10N, and 20N) on the physicochemical properties, matrix restructuring, and sustained-release behavior of bupropion hydrochloride (BUP·HCl)-loaded tablets. The extrudates were fabricated using HME, pelletized, and used as feedstock for screw-based 3D printing, thereby overcoming the limitations of filament-based systems. The formulations were evaluated for drug release, hardness, swelling, and porosity before and after dissolution using micro-computed tomography (microCT). The influence of tablet geometry on drug release was also investigated. Morphology, crystallinity, and thermal properties were characterized using scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). All formulations exhibited sustained BUP·HCl release, with drug release decreasing as EC viscosity grade increased. Tablets prepared with higher-viscosity EC showed greater hardness, reduced swelling, and lower post-dissolution porosity. MicroCT analysis revealed raster-related internal pores in all tablets before dissolution. However, initial porosity did not correlate with release behavior; tablets containing EC 20N exhibited the highest initial porosity but the lowest post-dissolution porosity and slowest drug release, whereas EC 7N tablets showed the opposite trend. Larger, thinner tablets released drug faster due to higher surface-area-to-volume ratio. The findings demonstrate that EC molecular weight plays a critical role in governing hydration-driven matrix restructuring and controlling sustained-release behavior of the 3D-printed tablets.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-026-03494-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148395254","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":"Vegetable Butter-Based Nanocarriers: Do Nanoparticulation and Quercetin Loading Modulate In vitro Cellular Effects Involved in Wound Healing?","authors":"Ana Beatriz Chieco Costa,&nbsp;Regina Gomes Daré,&nbsp;Luciana B. Lopes","doi":"10.1208/s12249-026-03490-8","DOIUrl":"10.1208/s12249-026-03490-8","url":null,"abstract":"<div><p>The need for advanced yet cost-effective topical strategies for chronic skin wounds motivated this study to evaluate nanostructured lipid carriers (NLCs) based on shea or cocoa butter. Our first goal was to compare NLCs with conventional emulsions to evaluate whether butter nanoparticulation confers biological advantages for wound-related applications. NLCs were produced by hot homogenization-sonication and characterized in terms of particle size, polydispersity, morphology, and stability. Both butter-based NLCs formed stable, monodisperse nanometric systems (size 197–240 nm, PDI &lt; 0.2). In HaCaT keratinocytes, shea and cocoa butter-based NLCs significantly enhanced proliferation (up to 137% for shea and 127% for cocoa butter) and wound repopulation (up to 96% and 65%, respectively) compared with the respective emulsions. Our second goal was to assess the effect of quercetin (QT) incorporation in the NLCs, since oxidative stress has been related to healing difficulties. QT incorporation did not further increase proliferation or repopulation but significantly improved antioxidant protection, reducing H₂O₂-induced intracellular reactive oxygen species by up to 53–62% at 12 µg/mL QT. Shea butter-based NLCs exhibited superior biological performance, including a modest intrinsic antioxidant effect (~ 15% DPPH inhibition), probably due to endogenous lipid bioactives. QT-loaded shea butter NLCs promoted enhanced QT retention within the stratum corneum (~ 14 vs. ~ 9 µg/cm²) and dermis (~ 9 vs. ~ 3 µg/cm²) of injured porcine skin while limiting permeation. These results demonstrate that vegetable butter-based NLCs, particularly from shea butter, represent a promising wound management platform that combines intrinsic lipid bioactivity, nanoscale-mediated drug availability, and skin barrier support.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-026-03490-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148395240","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":"Enhanced Stability and Transdermal Delivery of Semaglutide Using an L-Arginine Based Dissolving Microneedle System","authors":"Priyanka Panchal,&nbsp;Snehal Daware,&nbsp;Yi Guo,&nbsp;Ganming Mao,&nbsp;Blase Billack,&nbsp;Pulkit Khatri,&nbsp;Ketan Patel","doi":"10.1208/s12249-026-03455-x","DOIUrl":"10.1208/s12249-026-03455-x","url":null,"abstract":"<div><p>Glucagon-like peptide-1 agonists, especially Semaglutide (SMG), have revolutionized the management of diabetes and obesity, yet its clinical application is hindered by challenges in oral bioavailability and patient adherence to injectable formulations. Transdermal delivery offers a promising alternative, and this study explores dissolving microneedle (DMN) technology for SMG administration. PETOX is a water-soluble polymer utilized for the fabrication of dissolving microneedles and unique stabilization of SMG by incorporating L-arginine. Our study presents the first comprehensive investigation of L-arginine as an excipient in dissolving microneedles to enhance peptide integrity and stability. This study focuses on the development and characterization of DMN arrays formulated with a polymeric blend of hyaluronic acid, PETOX, and L-arginine, designed for the transdermal delivery of SMG. The SMG loaded microneedles (SMG-DMNs) exhibit robust mechanical strength (3.47 N/needle; fracture force), excellent Parafilm M® insertion (&gt; 50% at 450 μm depth), and drug release over 12 h. Extensive SMG-DMNs characterization include <i>ex-vivo</i> porcine skin insertion, scanning electron microscopy, confocal microscopy, and unique agarose-based dissolution model showed effective optimization of polymeric matrix for SMG, ensuring better insertion capabilities. The florescence imaging verified efficient transdermal deposition and penetration of dye suggesting potential transdermal delivery of SMG upon insertion. While the DMN approach addresses key barriers such as low oral bioavailability, injection-related discomfort and patient compliance; challenges persist regarding loss of therapeutic activity and stability of peptide. Nevertheless, DMN technology presents a promising, patient-friendly alternative for peptide therapeutics, with the potential to significantly improve outcomes in T2DM and obesity 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":"27 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374188","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}