AAPS PharmSciTech最新文献

{"title":"Intranasal Delivery of Cetrorelix Via Lipid Liquid Crystal Nanoparticles: Characterization and Pharmacokinetic Studies in Rats.","authors":"Soheil Tafazzoli Mehrjardi, Mohsen Tafaghodi, Saba Malek, Davood Yari, Amir Hooshang Mohammadpour, Hossein Kamali, Ali Nokhodchi","doi":"10.1208/s12249-025-03169-6","DOIUrl":"https://doi.org/10.1208/s12249-025-03169-6","url":null,"abstract":"<p><p>Nasal sprays are extensively researched due to their rapid absorption, high bioavailability, and low side effects. Lipid liquid crystal nanoparticles (LLCNs) are being considered as potential carriers for intranasal delivery. LLCs loaded with cetrorelix (GnRH antagonist) were utilized for intranasal drug delivery to enhance brain targeting while minimizing systemic exposure. A single-phase formulation incorporating HPMC as a mucoadhesive was developed to extend nasal residence time. Following intranasal administration of cetrorelix in rats, its distribution in various brain regions and serum was assessed using LC-MS-MS. In the LLC formulation, the particle diameter, PDI, and Zeta potential were measured as 204.92 ± 0.89 nm, 0.188 ± 0.019, and -21.63 ± 1.72 mV, respectively. A monomodal distribution and low polydispersity index were observed, along with a negative zeta potential. Cetrorelix was released from the LLC in a biphasic profile, with an initial burst release of 30%, followed by a gradual and sustained release phase. The LLCs containing cetrorelix exhibited lower cytotoxicity compared to the LLC base. The nasal administration of cetrorelix via LLCs presents a promising advancement for nose-to-brain drug transport. The pharmacokinetic data demonstrated that the AUC_0-360min for brain tissue analysis, following nasal administration of the single-phase formulation, was 3.104 ng/ml.min. The value was 7.104 ng/ml.min for LLC nasal administration and 6.104 ng/ml.min for subcutaneous injection. The maximum concentration (C_max) values for brain tissue analysis indicated a significant increase with LLC nasal administration (238 ± 6. 2 ng/ml) in comparison to the single-phase formulation (202.5 ± 6.3 ng/ml) and subcutaneous injection (218.2 ± 3. 1 ng/ml). In serum analysis, the C_max values were significantly elevated, with subcutaneous injection achieving (4983.3 ± 2.5 ng/ml), followed by LLC nasal administration at (93.1 ± 6.2 ng/ml), and the single-phase formulation at (43.7 ± 2.2 ng/ml). This innovative method aims to target the brain directly, eliminating the need for needles, and reducing adverse effects, hence offering new hope for brain-targeted drug delivery. This study introduces, for the first time, a cetrorelix-loaded lipid liquid crystal (LLC) nanoparticle formulation for intranasal nose-to-brain delivery. The LLC system achieved enhanced brain targeting efficiency while reducing systemic exposure compared to conventional subcutaneous injections and simple nasal formulations, representing a promising advancement in GnRH drug delivery strategies.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 6","pages":"176"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537714","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 the Local Drug Delivery Systems for Diabetic Wound Healing: A Comprehensive Review.","authors":"Reem Khaled Wassif, Rehab Nabil Shamma, Nada M El-Hoffy, Maha El-Kayal","doi":"10.1208/s12249-025-03172-x","DOIUrl":"https://doi.org/10.1208/s12249-025-03172-x","url":null,"abstract":"<p><p>Wound management in diabetic patients holds significant importance in both clinical and social contexts due to the delayed and compromised healing that these individuals experience. Diabetic wounds exhibit slow and incomplete healing, increasing patients' susceptibility to infections. Managing wounds in diabetic patients, particularly when complicated by diabetic foot infection or diabetic foot ulcer, becomes challenging. The ideal drug delivery systems for treating diabetic wounds should integrate diverse drugs and/or biological factors, offering advantages such as sustained and localized release of therapeutic compounds and enhanced wound healing outcomes. Several treatment modalities are under investigation for managing diabetic wounds, including advanced local drug delivery systems such as topical 3D scaffolds, particulate systems, and 3D scaffolds combined with particulate systems, in addition to gas therapy and skin grafts as advanced therapies. This review comprehensively discusses the state of the art for each treatment modality for diabetic wound healing associated with bioactive molecules. It also summarizes the forms of topically applied 3D scaffolds, including films, hydrogels, sponges, nanofibers, wafers, microneedles, and foams. The review differentiates their advantages and disadvantages as topical therapies while discussing various scaffold types that integrate therapeutic agents, which include polymeric, inorganic, composite, and biological scaffolds. With the emphasis on the newly investigated locally administered drug delivery systems for the management of diabetic wounds, the review also focuses on the challenges and the future perspectives for the production of such systems with the use of various drugs and biomaterials using innovative technologies such as 3D printing for effective healing of wounds.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 6","pages":"177"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537716","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":"Formulation Development and Characterization of Bigels Containing Curcumin for Topical Skin Delivery.","authors":"Lord Sam Liston, Suranate Phanapithakkun, Nuttakul Pimsarn, Nuttapon Dangkaokhia, Thanat Nakasan, Attawadee Sae Yoon, Hiroaki Todo, Teerapol Srichana, Somchai Sawatdee, Gerard Lee See, Florencio Arce, Pajaree Sakdiset","doi":"10.1208/s12249-025-03166-9","DOIUrl":"https://doi.org/10.1208/s12249-025-03166-9","url":null,"abstract":"<p><p>Curcumin, a pleiotropic molecule, has been reported to modulate skin health and functions owing to its anti-inflammation, wound healing, antimicrobial, and anti-aging effects. Curcumin, a lipophilic molecule, exhibits poor skin penetration that results in decreased efficacy in treating skin diseases. In this study, a bigel containing curcumin was formulated to enhance skin deposition of curcumin. Generally, bigels are composed of hydrogel (HG) and organogel (OG) and feature the ideal characteristics of both systems. The HG contained HPMC 2% w/v, and the OG contained Span® 60, almond oil, and curcumin (0.25%) mixed in different HG:OG proportions from 90:10 to 10:90. Three ratios of HG:OG, BG50 (50:50), BG40 (60:40), and BG30 (70:30) successfully formed yellowish turbid smooth bigels. The bigels were characterized as an o/w system with microdroplet size (7.10-30.60 µm) under a microscope. All bigel formulations showed pseudoplastic behavior and had low oil leaching. Skin permeation experiments revealed that BG30 provided the highest curcumin accumulation in the stratum corneum, and viable epidermis and dermis, which was higher than the control OG for 1.61 ± 0.17 and 3.63 ± 0.89-fold, respectively. All bigels were nontoxic on the murine fibroblast cell line L929 at 62.5-1,000 μg/mL of curcumin. B30 provided the highest wound healing effect as determined by the L929 scratch assay. The % migration increased to 70.11 ± 1.11 at 24 h and to 100% at 48 h. These findings suggest that BG30 could be potentially used to deliver curcumin intended for topical applications.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 6","pages":"175"},"PeriodicalIF":3.4,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511398","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":"Design of Passion Fruit Oil Emulgel for Topical Chrysin Delivery and Ex Vivo Evaluation of Skin Permeation by Photoacoustic Spectroscopy.","authors":"Bruna Gheller de Souza, Lidiane Vizioli de Castro Hoshino, Thalita Schilive Faccin, Mauro Luciano Baesso, Fernanda Belincanta Borghi-Pangoni, Marcos Luciano Bruschi","doi":"10.1208/s12249-025-03164-x","DOIUrl":"https://doi.org/10.1208/s12249-025-03164-x","url":null,"abstract":"<p><p>Chrysin, a flavonoid effective against various skin cancers, displays poor solubility, skin permeation, and bioavailability. Emulgel emerges as an innovative and promising strategy for the topical administration of chrysin, offering significant advantages over existing systems. Passion fruit oil (PFO) enhances topical formulations with improved safety, compatibility, and drug delivery. However, current emulgels raise safety concerns due to their surfactant, co-surfactant, and oily co-solvent content. This study aimed to develop innovative emulgel containing PFO, without unsafe surfactants, for the topical delivery of chrysin. ATR-FTIR and DSC analyses of chrysin and excipients were performed. A 3³-factorial design was used, and the formulations were evaluated for preliminary physicochemical stability, mechanical and rheological properties, in-vitro release profile of chrysin, bioadhesion and ex-vivo skin permeation by photoacoustic spectroscopy (PAS). ATR-FTIR and DSC analyses confirmed the compatibility of chrysin with the formulation excipients. Formulations F6, F11, and F21 were stable and exhibited hardness (0.2006-0.4299 N), compressibility (1.4737-3.4300 N.mm), elasticity (0.9924 - 1.0034 mm), adhesiveness (0.8077-2.2217 N.mm), cohesiveness (0.7637 - 0.8733), softness index (0.0648 - 0.1525 N), and bioadhesive strength (0.0648 - 0.0754 N), both values with relative standard deviation less than 9%. They were pseudoplastic with yield value, thixotropy, and viscoelasticity. Chrysin release profile was slow and governed by anomalous transport. PAS analysis showed chrysin could permeate the stratum corneum and epidermis, reaching the dermal layer. The selected emulgels are promising for effective topical application, and the formulation F21 standing out in particular for further both in vitro and in vivo biological evaluations.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 6","pages":"173"},"PeriodicalIF":3.4,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504366","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":"Co-delivery of Exemestane and Genistein via Chitosan Coated Liposomes for Enhanced Antitumor Effect and Bone Loss Prevention in Breast Cancer Therapy: In Vivo Evaluation.","authors":"Shwetakshi Sharma, S M Kawish, Priya Gupta, Shreshta Jain, Shahnawaz Ahmad, Zeenat Iqbal, Divya Vohora, Kanchan Kohli","doi":"10.1208/s12249-025-03163-y","DOIUrl":"10.1208/s12249-025-03163-y","url":null,"abstract":"<p><p>Breast cancer (BC) is the most prevalent form of cancer among women worldwide, accounting for approximately 36% of cancer cases. Due to its inimitable pathological expression and restricted success of accessible therapeutic modalities, fanatical research in this area is essential. Our group has developed a nanovesicular lipid carrier system consisting of Exemestane (EXM) and Genistein (GNS), which have been successfully incorporated into both uncoated and chitosan-coated liposomes. This combination aims to enhance anticancer efficacy. EXM is known to cause bone loss, while GNS, a natural isoflavone, has been shown in research to possess bone-protective effects. Therefore, we combined these two compounds to mitigate the side effects of EXM. Our previous publication details the formulation development of uncoated EXM-GNS liposomes (EXM-GNS-LPS) and chitosan-coated EXM-GNS liposomes (CH-EXM-GNS-LPS), where we addressed the pharmacotechnical challenges of combining a synthetic drug with herbal drug. Both uncoated and coated liposomes were tested for their budding effects on bone loss induced by hormonal therapy. Pharmacokinetic and pharmacodynamic studies were conducted on rat models with breast cancer, treated with different formulations. Biochemical investigations revealed significant changes in biomarker levels, indicating effects on bone development and resorption. Improvements in bone health and anticancer efficacy were observed to be statistically significant (p < 0.05). Micro-CT analysis of bone samples showed that the chitosan-coated EXM-GNS liposome treatment group yielded the best results when evaluate against other treatment groups. Additionally, histological examination of the bone treated with CH-EXM-GNS-LPS demonstrated a marked restoration of trabecular bone architecture, characterized by a well-connected bone matrix and narrower inter-trabecular spaces compared to the toxic control group. The synergistic effect of EXM and GNS, encapsulated in liposomes, offers an innovative solution to the challenges of breast cancer treatment. The chitosan coating not only improved the stability and controlled release of the drugs but also provided additional benefits in terms of biocompatibility and targeting potential. Overall, the results of this study indicate that the CH-EXM-GNS-LPS formulation holds significant promise as a therapeutic and preventive strategy for bone loss associated with hormonal therapy in breast cancer patients. This work lays the foundation for future clinical applications, highlighting the potential for combining synthetic and natural compounds in advanced drug delivery systems to address complex, multifactorial health issues.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 6","pages":"174"},"PeriodicalIF":3.4,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511397","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":"Phospholipid Complex-based Topical Gel for Codelivery of Erlotinib and Methotrexate in Psoriasis.","authors":"Sanyog Jain, Shivani Mali, Junia Akhtar, Chander Parkash Dora, Rahul R Mahajan","doi":"10.1208/s12249-025-03168-7","DOIUrl":"https://doi.org/10.1208/s12249-025-03168-7","url":null,"abstract":"<p><p>Topical drug delivery systems offer a targeted and patient-compliant approach for managing psoriasis, enabling noninvasive, localized, and sustained therapy, with reduced systemic side effects and improved therapeutic outcomes. In this study, we prepared phospholipid complex (PLC) based gel of methotrexate (MTX) and erlotinib (ERL) as a potential dual treatment for psoriasis. The phospholipids used in this study were biocompatible and exhibited enhanced skin permeation. The physical interactions between drugs and phospholipids in the MTX-loaded phospholipid complex (MPLC) and ERL-loaded phospholipid complex (EPLC) were characterized by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (¹H NMR), and powder X-ray diffraction (P-XRD). Scanning electron microscopy (SEM) confirmed amorphization of the drug upon complexation, and transmission electron microscopy (TEM) indicated that the complexes formed a spherical morphology. Furthermore, gel-embedded drug-phospholipid complexes exhibited slower diffusion-based sustained release profiles, with ~ 40% release of ERL from EPLC and ~ 60% release of MTX from MPLC over 24 h, in contrast to the faster release of ~ 65% and ~ 90% observed for free ERL and MTX, respectively. Skin permeation studies (Franz diffusion cells), dermal pharmacokinetics studies, and in vivo antipsoriatic activity studies (imiquimod (IMQ)-induced psoriasis model) were performed to evaluate the efficacy of the optimized formulation. This first-in-class combination therapy provides better lesion control and reduced inflammation while minimizing systemic adverse effects, highlighting the potential of drug-phospholipid complexes for targeted, sustained delivery in psoriasis treatment.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 6","pages":"172"},"PeriodicalIF":3.4,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504368","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 In Vitro Characterization of Azithromycin-PLGA Nanoparticles Loaded Thermoresponsive Hydrogels: A Quality by Design Approach Toward Intra-Articular Delivery of Macrolides.","authors":"Bao Ngoc Tran, Cam Le Ha, Duyen Thi Thuy Vu, Chien Ngoc Nguyen","doi":"10.1208/s12249-025-03170-z","DOIUrl":"https://doi.org/10.1208/s12249-025-03170-z","url":null,"abstract":"<p><p>Azithromycin (AZT), a macrolide antibiotic, has recently been explored as an injection therapy for osteoarthritis. However, its instability and poor solubility limit its effect due to an insufficient quantity and duration at the target sites. To address these challenges, this study developed poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) for AZT delivery, which were subsequently incorporated into a thermoresponsive injectable hydrogel suitable for intra-articular administration. The formulation was developed using a Quality by Design (QbD) approach, focusing on two steps: (i) preparation of AZT-PLGA NPs and (ii) loading the NPs into a poloxamer-based hydrogel. Critical material attributes (AZT, PLGA, surfactants) were evaluated for their impacts on the critical quality attributes (CQAs) of the NP formulation (size distribution and encapsulation efficiency). The optimized AZT-PLGA NPs exhibited a mean particle size of ~ 150 nm and a PDI of < 0.2, ensuring uniformity and stability. Secondly, these NPs were then embedded into a novel thermoresponsive hydrogel. The effects of NPs, hyaluronic acid, and mannitol on physical appearance, thermal sensitivity, the rheology (shear-thinning and thixotropic), pH, and sustained release properties of the final formulation were systematically investigated. Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analyses revealed interactions between AZT and PLGA, which, while not affecting the drug assay, enhanced the structural integrity and modified the thermal properties of the final product. Using QbD principles, a risk-based assessment was proposed for future drug development. This study introduced a novel thermoresponsive injectable hydrogel for the intra-articular delivery of AZT using PLGA nanoparticles.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 6","pages":"171"},"PeriodicalIF":3.4,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504367","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":"Optimizing Extended-release Formulation of l-tetrahydropalmatine Based on In Vivo Outcomes Using Integrated Modeling Approaches.","authors":"Thi-Phuong-Dung Pham, Huy Minh Dao, Nguyen-My-Linh Pham, Thanh-Vinh Dang, Hoang-Anh Nguyen, Cao-Son Tran, Linh Nguyen Tran, Nguyen-Thach Tung","doi":"10.1208/s12249-025-03165-w","DOIUrl":"https://doi.org/10.1208/s12249-025-03165-w","url":null,"abstract":"<p><p>l-Tetrahydropalmatine (l-THP) is a promising drug candidate for addiction treatment and needs to be delivered in extended-release dosage forms for safety and efficiency. This study aims to optimize extended-release formulations containing l-THP to achieve desired in vivo outcomes (C_max, onset of action, and duration of action) by integrating multiple computational tools including in vitro-in vivo correlation (IVIVC), physiologically based pharmacokinetic (PBPK), and design of experiments (DoE). The in vivo predictable dissolution method was chosen based on level A IVIVC. Then, PBPK model was developed and validated to explore the influences of physiological and formulation factors on the bioavailability of l-THP from hydrophilic matrix tablets. Finally, the PBPK model was incorporated with DoE to investigate the impact of formulation variables on in vivo outcomes and optimize the hydrophilic matrix tablet formulation for desired C_max, start time of action, and duration of action. USP Apparatus I, 450 ml HCl 0.1 N, 100 rpm demonstrated the highest level of correlation between in vitro dissolution and in vivo absorption, among the tested conditions. The PBPK model accurately predicted l-THP pharmacokinetics, meeting U.S.FDA requirements for prediction errors. The PBPK model identified dissolution parameters and gut first-pass extraction as key factors affecting l-THP bioavailability. The optimized formulation was estimated to exhibit an early onset of action (0.68 h), remain effective for more than 11.4 h, and be safe with C_max consistently falling within the therapeutic window. The present approach can be applied to design other drug delivery systems for flexible in vivo outcomes.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 6","pages":"170"},"PeriodicalIF":3.4,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493362","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, Characterization, and Molecular Dynamics Simulation of Andrographolide Nanosuspensions Utilizing Hummer Acoustic Resonance Technology.","authors":"Li Wang, Xiaoyang Zhang, Jianlu Qu, Zhanrui Zhang, Wei Wu, Wenlong Li","doi":"10.1208/s12249-025-03160-1","DOIUrl":"10.1208/s12249-025-03160-1","url":null,"abstract":"<p><p>Andrographolide (AG) is a diterpenoid lactone, widely recognized for its potent anti-inflammatory and immunomodulatory properties. However, AG's clinical applications are significantly limited due to its poor water solubility. The aim of this study was to rapidly develop an andrographolide nanosuspension (AG-NS) using Hummer Acoustic Resonance (HAR) technology to enhance AG's solubility. AG-NS was prepared using HAR technology for high-throughput screening of stabilizers. Quality risk assessment was performed to identify critical formulation and process variables influencing AG-NS. A Box-Behnken design (BBD) was applied to evaluate the effects of these critical variables on AG-NS. Following lyophilization, the redispersibility of AG-NS was evaluated, and physicochemical characterization was conducted to verify the absence of significant interactions between AG and the excipients. The optimized AG-NS formulation exhibited a Z-Ave of 183.96 ± 4.40 nm, a PDI of 0.151 ± 0.065, and a zeta potential of -42.85 ± 1.09 mV. MD simulations revealed the internal mechanisms of AG-NS stabilization. Lyophilized AG-NS demonstrated excellent redisperseability. In vitro dissolution studies showed that the lyophilized AG-NS had a significantly faster dissolution rate and higher cumulative dissolution (120 min) compared to AG crude powder and the physical mixture (PM). The optimized AG-NS demonstrated favorable physicochemical properties and enhanced dissolution performance. The lyophilized formulation exhibited excellent redispersibility upon reconstitution. HAR technology is an innovative and efficient approach for the rapid development and optimization of nanosuspension formulations.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":"169"},"PeriodicalIF":3.4,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293143","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":"Taste Masking of Primaquine Phosphate: A Comparative Evaluation of Three Taste Masking Agents.","authors":"Galande Ankit, Gagare Tejashree, Sahu Surbhi, Kulkarni Madhur","doi":"10.1208/s12249-025-03162-z","DOIUrl":"10.1208/s12249-025-03162-z","url":null,"abstract":"<p><p>The work involved taste masking of primaquine phosphate (PMQ), an intensely bitter drug used in the prevention and treatment of relapses of malarial infections caused by Plasmodium vivax and ovale. Drug and cation exchange resins viz, AmberLite™ IRP 64, 69, and 88 (IER 64, IER69, and IER88) were subjected to complex formation in 1:1 and 1:2 ratios using the shake flask method. Inclusion complexes of PMQ with hydroxypropyl beta cyclodextrin (HPBCD) were prepared to employ co-grinding, kneading, co-evaporation, and spray drying methods. Solid dispersions of PMQ with Eudragit E 100 (E 100) were prepared in various ratios by spray drying. In vitro, drug release studies of the composites were performed in 0.1N HCl and pH 6.8 phosphate buffer. The composites showing the least drug release in pH 6.8 buffer without compromising the release in an acidic medium were also evaluated for drug release in simulated salivary fluid (SSF). The selected composites were formulated into orally disintegrating tablets (ODTs) and subjected to human panel taste evaluation. PMQ-HPBCD spray-dried complex, PMQ-IER 69 (1:2) complex, and PMQ-E100 (1:4) dispersion exhibited drug release in decreasing order in SSF but > 85% release within 1 h in an acidic medium. Hence, these composites were formulated into ODTs. The human panel tasting indicated the most acceptable taste of the ODTs comprising PMQ-E 100 dispersion followed by PMQ- IER 69 (2) complex, and lastly PMQ HPBCD complex. The PMQ-E100 dispersion-based ODTs could thus be a promising option for treating pediatric and geriatric patients with PMQ.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":"168"},"PeriodicalIF":3.4,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273926","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}