AAPS PharmSciTech最新文献

{"title":"Unveiling the Potential of Nanoclays in Pharmaceuticals.","authors":"Rabab Kamel, Giuseppina Nocca, Elena Mazzinelli, Somaia S Abd El-Karim, Valerio Papa, Ilaria Cacciotti, Nermeen A Elkasabgy","doi":"10.1208/s12249-025-03157-w","DOIUrl":"10.1208/s12249-025-03157-w","url":null,"abstract":"<p><p>Clay minerals or nanoclays are layered aluminosilicate nanoparticles with unique physicochemical properties, excellent biocompatibility, high surface area, lamellar structure, diverse ion-exchange capacity, tuneable surface chemistry enabling them to form different intermolecular interactions which offer supreme prospects for optimized pharmaceutical applications. This review article dives into the key characteristics of different types of nanoclays like Halloysite, Kaolinite, Sepiolite, Montmorillonite, Bentonite and Laponite, highlighting their possible exploitation within the pharmaceutical landscape. Also, the review describes the recent advances in nanoclay-based drug delivery systems and discusses the role of nanoclays as drug carriers and their use in tissue engineering and gene therapy. Nanoclays, are used to modulate drug release and stabilize the loaded active molecules as well as to enhance drug loading. Interdisciplinary research, advanced characterization techniques, and careful formulation designs are required to augment the use of nanoclays in various pharmaceutical applications. Despite the faced challenges, research on nanoclay-based drug delivery systems is growing. With targeted research and development, nanoclays are poised to redefine the biomedical domain, offering tailored and efficient therapies for a multitude of diseases.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":"167"},"PeriodicalIF":3.4,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265019","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":"Development and Evaluation of Huperzine A-Loaded Microneedles for Transdermal Delivery and Pretreatment of GD Poisoning.","authors":"Guixiang Yang, Yi Zhang, Chong Li, Xingle Xia, Qian Jin, Liqin Li, Xingxing Zong, Dongxin Liu, Jingchen Wei, Xuejun Chen, Chen Wang","doi":"10.1208/s12249-025-03149-w","DOIUrl":"10.1208/s12249-025-03149-w","url":null,"abstract":"<p><p>Huperzine A (Hup A), a reversible acetylcholinesterase inhibitor, shows protective potential against neurotoxic poisoning. Current formulations (oral tablets/capsules and injectables) face limitations: oral administration suffers from first-pass metabolism and fluctuating plasma concentrations due to frequent dosing, while injectables require sterile administration, reducing long-term compliance. The aim of this study was to prepare dissolving microneedles (MNs) patches containing Hup A for pretreatment against soman (GD) poisoning. Hyaluronic acid (HA), polyvinylpyrrolidone K30 (PVP K30) and sorbitol were selected as matrix materials in specific proportions and concentration ranges based on single-factor screening experiments and orthogonal design optimization. In order to further evaluate the potential of the Hup A MNs, optimized formulations were selected for subjected to characterization. This evaluation encompassed morphological observation, mechanical properties, skin penetration efficacy, recovery time, in vitro drug release study, permeability assays, pharmacokinetic study, and pharmacodynamic study. Statistical analyses were performed using Student's t-tests for pairwise comparisons and one-way ANOVA for multiple comparisons. The results demonstrated that prepared Hup A MNs had a conical shape with a smooth surface and sharp tips. Hup A MNs had sufficient mechanical strength (122.3 ± 15.3 N) to penetrate through the skin and could be quickly skin of recovery 6 min. In permeability assays, the cumulative Hup A release was about 35.4 μg at 2 h and 58 μg at 10 h. Pharmacodynamic results demonstrated that compared to oral administration, Hup A MNs reduced the onset time (30 min vs. 60 min) and extended the effective prevention duration against GD poisoning (6 h vs. 2 h). Pharmacokinetic analysis showed that MNS administration can maintain a more lasting and stable blood concentration as compared to oral administration. MNs are a valuable drug delivery system, benefiting the patients with minimal skin invasion. Taken together, these results demonstrated that Hup A-loaded MNs are acquiring a new alternative for pretreatment of OPNAs.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":"164"},"PeriodicalIF":3.4,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245668","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":"Nanosizing and Surface Modification by Propellant Assisted Aerosolization Enhances Solubility and Dissolution of Estradiol.","authors":"Gaurav K Jain, Gaurav Chaudhary, Mohammad Akhlaquer Rahman, Musarrat Husain Warsi, Mohammad Imran","doi":"10.1208/s12249-025-03151-2","DOIUrl":"10.1208/s12249-025-03151-2","url":null,"abstract":"<p><strong>Objective: </strong>A novel method for the development of uniform, nanosized, crystalline particles of estradiol valerate (EV) by the propellant assisted aerosolization (PAA) technique as an alternative to supercritical carbon dioxide assisted atomization is described.</p><p><strong>Methods: </strong>HFA 134a was used as a propellant. PAA process parameters such as nozzle diameter, pre-expansion pressure, and hot air pressure were optimized using 33 factorial Box-Behnken design for the preparation of uniform, nanosized EV (nano-EV). Nano-EV was characterized for physicochemical properties, crystallinity and enhancement of the solubility and dissolution.</p><p><strong>Results: </strong>The nano-EV, produced by the PAA technique, showed loose cuboidal aggregates with smooth surface morphology. PAA with 0.22 µm nozzle diameter, 120 psi pre-expansion pressure and 80 psi hot air pressure, yielded uniform (PDI, 0.27 ± 0.05) nano-EV particles with mean size of about 291 ± 5.8 nm. FTIR and DSC confirmed that no physical or chemical change occurred during nanosizing. XRD data showed that nano-EV particles were crystalline. The results demonstrated nearly twofold higher solubility and 2.3-fold enhanced dissolution of nano-EV compared to EV.</p><p><strong>Conclusion: </strong>The PAA process is a cost effective and scalable technique and has a potential industrial application for producing nanocrystals of BCS class II drugs.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":"165"},"PeriodicalIF":3.4,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245669","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":"Skin can Modulate the pH of Topical Creams and Gels.","authors":"Sanjeevini M, Harini Priya Pa, Rakshitha L, Prajwal N Murthy, Pragathi S G, Anusha V Matadh, Srujana N Murthy, Srinath R, Shivakumar H N, Howard Maibach, S Narasimha Murthy","doi":"10.1208/s12249-025-03161-0","DOIUrl":"10.1208/s12249-025-03161-0","url":null,"abstract":"<p><p>The pH of the formulation can affect the pH of the skin surface. However, the skin's pH is known to recover rapidly due to the substantial buffer capacity associated with the skin. The objective of the project was to investigate the effect of the buffer capacity of skin on the pH of the formulation. A few custom-made gel and cream formulations were used as test products in the study. Custom-made gel and cream formulations were prepared and applied to human skin, with parallel applications on an inert substrate serving as controls to isolate the effect of solvent evaporation. In the control group, pH changes due to evaporation were negligible across all formulations. In vivo application revealed that the skin's buffering capacity significantly modulates the pH of the applied formulation. When formulations had a pH higher than the skin's basal level, the skin responded by reducing the formulation pH. For instance, a cream adjusted to pH 9 showed a drop of more than one pH unit within 30 min post-application. Conversely, formulations with pH lower than the skin's baseline exhibited an increase in pH; creams adjusted to pH 4 increased by over 0.5 units in the same timeframe. This bidirectional shift highlights the skin's active role in restoring pH homeostasis. The incorporation of buffers with varying ionic strengths into the formulations reduced the extent of pH drift, offering greater resistance to skin-driven pH changes compared to unbuffered formulation.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":"166"},"PeriodicalIF":3.4,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245670","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: Laser-mediated Solutions: Breaking Barriers in Transdermal Drug Delivery.","authors":"Ehsan Haghsay Khashechi, Abolfazl Afaghmehr, Niloofar Heidarizade, Ashkan Barfar, Javad Shokri","doi":"10.1208/s12249-025-03125-4","DOIUrl":"10.1208/s12249-025-03125-4","url":null,"abstract":"","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":"161"},"PeriodicalIF":3.4,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144223925","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":"Application of Physiologically Based Biopharmaceutics Modeling (PBBM) to Establish Clinically Relevant Dissolution Specifications for a Prolonged Release Tablet Formulation of Verapamil, a BCS Class I Drug.","authors":"Anagha Damre, Aniruddha Banerjee","doi":"10.1208/s12249-025-03156-x","DOIUrl":"10.1208/s12249-025-03156-x","url":null,"abstract":"<p><p>Our work aimed at setting clinically relevant dissolution specifications for a prolonged release formulation of verapamil, a BCS Class I drug. We have used a two-pronged approach- a Level A IVIVC correlation supplemented with virtual bioequivalence assessment using Physiologically based biopharmaceutics modelling (PBBM). Dissolution studies were performed for two batches, Medium-release (BE batch) and Slow-release (non-BE batch), using a biorelevant method. Mechanistic absorption deconvolution method was used to obtain the in vivo release profiles and correlate with the respective in vitro release profiles to develop the IVIVC. Theoretical dissolution profiles for upper and lower limits were generated and used for convolution and calculation of Percent prediction errors (%PE). This was supplemented with virtual bioequivalence (VBE) assessments at each level to select clinically relevant dissolution specifications. A two-step deconvolution-correlation method resulted in a linear Level A IVIVC with R² = 0.951 which was internally and externally validated. Percent prediction errors (%PE) for C_max and AUC were calculated for each level to accept/reject the limits. VBE trials showed that the 90% CI fell within the acceptable limits of 80-125% for C_max, AUC_0-t and AUC_0-inf for the lower dissolution specification limit 5 and for the upper specification limit 3. The current investigation demonstrates new opportunities offered by mechanistic modelling and how this two-pronged approach (IVIVC and IVIVR-VBE) can be used to define clinically relevant dissolution specifications and the BE safe space, which can support post-approval changes for waiving bioequivalence studies and ensuring commercial product quality over the years.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":"163"},"PeriodicalIF":3.4,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144223924","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":"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":"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":"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":"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":"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}