AAPS PharmSciTech最新文献

{"title":"Novel Methods Developed in Bioequivalence Assays: Patent Review","authors":"Brian Sebastian Correa Barrera,&nbsp;Izabel Almeida Alves,&nbsp;Diana Marcela Aragón","doi":"10.1208/s12249-025-03079-7","DOIUrl":"10.1208/s12249-025-03079-7","url":null,"abstract":"<div><p>This study examines advancements in bioequivalence (BE) assessment methods, with a focus on <i>in vitro</i>-<i>in vivo</i> correlation (IVIVC) and dissolution testing technologies. A systematic patent search was conducted via Espacenet, following PRISMA criteria and the study objectives, revealing 216 relevant patents, of which 28 were selected based on their contributions to novel BE methodologies. Analysis indicates a rapid increase in patent filings from 2021 to 2022, with a significant concentration of contributions from China. Key innovations include enhancements in dissolution testing apparatus, application of physiologically based pharmacokinetic (PBPK) modeling for IVIVC, and advanced statistical approaches for BE assessment. In dissolution testing, ƒ1 and ƒ2 factors remain essential metrics for assessing similarity, especially in solid oral dosage forms. These innovations enhance the efficiency (streamline) of BE evaluations, optimizing the biowaiver process and minimizing the need for extensive clinical trials while ensuring greater precision and reliability. The dissolution test, particularly when combined with PBPK models, allows for predictive evaluation of formulation changes and population-specific responses, fostering efficiency in drug development. Overall, these novel BE assessment approaches provide a framework for regulatory compliance, cost-effective production, and assurance of therapeutic equivalence in generic formulations. While they may not always be implemented in practice, they contribute significantly to innovation in the field, driving advancements in bioequivalence evaluation. This review highlights the evolving landscape of BE and IVIVC methodologies and underscores the importance of incorporating innovative testing approaches to advance pharmaceutical science and regulatory practices.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698685","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":"Engineering pH-Dependent Orally Disintegrating Tablets for Modified Indomethacin Release: A Polymer-Based Approach","authors":"Nihad Al-hashimi,&nbsp;Eman Zmaily Dahmash,&nbsp;Mouhamad Khoder,&nbsp;Raid Alany,&nbsp;Amr Elshaer","doi":"10.1208/s12249-025-03082-y","DOIUrl":"10.1208/s12249-025-03082-y","url":null,"abstract":"<div><p>The application of pH-sensitive polymers has been widely explored in pharmaceutical industry because of their versatile properties. This work aims to delay the release of indomethacin (IND), a commonly used anti-inflammatory drug, using a pH-dependent polymer within orally disintegrating tablets (ODTs) and to investigate the effect of the polymer particle size on the ODTs. When developing delayed-release formulations for orally disintegrating tablets (ODTs), it's essential to balance the pellet's matrix properties to maintain integrity and delayed release. Different sizes of Eudragit L100 were used to create IND-containing pellets via extrusion spheronization, which were then embedded into the matrix of ODTs. The particle sizes displayed good elastic properties with low Young's modulus (YM) values, and there was no significant difference between the different sizes (45, 60, 93 µm; <i>p</i> &gt; 0.05). The tensile strength of the pellets was directly proportional to YM (<i>p</i> &lt; 0.05), providing enough support to maintain their integrity under compression. Pellets made from 63 µm Eudragit L100 had a suitable balance of mechanical and pharmaceutical properties compared to other sizes. 63 µm pellets had an aspect ratio of 1.49 ± 0.26 and 61% yield, while their ODTs showed a fast disintegration time of 14 ± 0.6 s, while modifying the drug release. Furthermore, IND exhibited modified release in acidic media (pH 1.2) and immediate release in buffer media (pH 6.8). Overall, protecting pellet integrity was crucial to delay release in acidic media and enable immediate release in alkaline media. The newly developed formulation will improve compliance and reduce side effects associated with IND and other irritant drugs particularly in elderly populations.</p><h3>Graphical Abstract</h3><p>Graphical illustration for developing delayed release indomethacin loaded Eudragit L100 pellets embedded in orally disintegrating tablets\u0000</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03082-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706928","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":"Amorphous Solid Dispersion/Salt of Efavirenz: Investigating the Role of Molecular Interactions on Recrystallization and In-vitro Dissolution Performance","authors":"Aastha Gadoya,&nbsp;Kiran Dudhat,&nbsp;Sunny Shah,&nbsp;Chetan Borkhataria,&nbsp;Trupesh Pethani,&nbsp;Viral Shah,&nbsp;Nilesh Janbukiya,&nbsp;Saina Jyotishi,&nbsp;Jainabparvin Ansari,&nbsp;Mori Dhaval","doi":"10.1208/s12249-025-03084-w","DOIUrl":"10.1208/s12249-025-03084-w","url":null,"abstract":"<div><p>Efavirenz (EFZ), a BCS (Biopharmaceutical classification system) class-II/IV drug, suffers from low oral bioavailability (40–50%) and significant inter/intra-individual variability due to its low solubility and poor dissolution properties. The present investigation aimed to prepare a stable amorphous system of EFZ to improve its dissolution using the slurry method with various polymers and examine the nature of the interaction between them and its impact on the stability (recrystallization) of the formed systems and their <i>in-vitro</i> dissolution performance. Differential Scanning Calorimetry (DSC) and Powder X-ray Diffraction (PXRD) studies proved the formation of a complete amorphous system of EFZ with Eudragit® E100, HPMC E5, and HPMCAS-LF up to 50% drug loading. During 90 days accelerated stability studies, amorphous systems prepared using Eudragit® E100 remained stable at 50% drug loading however those prepared with HPMC E5, and HPMCAS-LF only remained stable at 25% drug loading. The ability of Eudragit® E100 based system to stabilize the drug at higher drug loading was attributed to the formation of stronger ionic interaction as revealed by the Fourier-transform infrared spectroscopy (FTIR) study. During <i>in-vitro</i> dissolution study, Eudragit® E100 based amorphous system generated and maintained significantly higher supersaturation compared to those prepared with HPMC E5, and HPMCAS-LF due to the formation of ionic interaction between EFZ and Eudragit® E100 as revealed by solution ¹H NMR study.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645407","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 Optimization of Eberconazole Nanostructured Lipid Carrier Topical Formulations Based on the QbD Approach","authors":"Amarnath Reddy Ramireddy,&nbsp;Dilip Kumar Behara","doi":"10.1208/s12249-025-03083-x","DOIUrl":"10.1208/s12249-025-03083-x","url":null,"abstract":"<div><p>Eberconazole nanostructured lipid carrier (EBR-NLC) 1% w/w optimization was done using the Quality by Design (QbD) approach, employing a 2³ Full Factorial Design (FFD) for experimental planning, followed by thorough physico-chemical, in-vitro, and ex-vivo evaluations. The 2³ FFD assessed the impact of total lipid amount, surfactant amount, and sonication time on critical quality attributes such as particle size and % entrapment efficiency. <i>In-vitro</i>release testing (IVRT) validation was performed using vertical diffusion cells. IVRT, a compendial technique by pharmacopoeias, was for performing semi-solid formulations analysis. The optimized EBR-NLC 1% w/w was characterized for assay, organic impurities, amplitude sweep, viscosity, IVRT, ex-vivo permeation testing, and skin retention. The validated IVRT technique was meeting the acceptance criteria of regulatory guidelines. The results showed that in-vitro release, ex-vivo permeation, and skin retention were significantly higher (<i>P</i> &lt; 0.05) for the optimized EBR-NLC 1% w/w formulation compared to the innovator formulation (EBERNET^® Cream 1% w/w). Applying QbD principles systematically facilitated the successful development and optimization of an EBR-NLC 1% w/w. The optimized EBR-NLC 1% w/w formulation proved to be a viable alternative, showing stability for at least six months under conditions of 40°C/75% RH and 30°C/75% RH.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645409","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":"Quantitative Analysis of Salmon Calcitonin Hydroxyapatite Nanoparticle Permeation to substantiate Non-Invasive Bone Targeting via Sublingual Delivery","authors":"Darsheen Kotak,&nbsp;Esha Attar,&nbsp;Bhavik Dalal,&nbsp;Aruna Shankarkumar,&nbsp;Padma Devarajan","doi":"10.1208/s12249-025-03068-w","DOIUrl":"10.1208/s12249-025-03068-w","url":null,"abstract":"<div><p>We earlier reported comparable efficacy in bone parameters of sublingually administered salmon calcitonin hydroxyapatite nanoparticles (SCT-HAP-NPs) compared to the subcutaneous injection, in the ovariectomy rat model, despite a bioavailability of barely ~ 15%. We ascribed this intriguing finding to targeted bone delivery, facilitated by translocation of significant quantity of intact NP into systemic circulation. In the present study we track the translocation of FITC-SCT-HAP-NPs (~ 100 nm) across porcine sublingual mucosa using the Franz diffusion cell to validate our hypothesis. Confocal Laser Scanning microscopy (CLSM) established that SCT-HAP-NPs permeated into the deeper layers of sublingual porcine mucosal tissue. We confirmed the nanoparticles were present in the receptor medium of the Franz diffusion cell by DLS and TEM. We also demonstrate for the first time quantification of the NPs (%) translocated across the porcine mucosa, using the Amnis Image StreamX Mk II imaging flow cytometer. Computation revealed transport of ~ 60% of the FITC-SCT-HAP-NPs across mucosa in 2 h, substantiated that high NP concentrations could reach systemic circulation. Such high NP concentration in systemic circulation coupled with the small size (~ 100 nm) and the high bone affinity of HAP, validate our hypothesis of targeted bone delivery following sublingual administration. Furthermore, quantification of translocated NPs, which we demonstrate for the first time, would permit rational development of optimal targeted nanoparticulate carriers for delivery by noninvasive routes.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645408","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":"Brazilian Green Propolis Extract-Loaded Poly(Ε-Caprolactone) Nanoparticles Coated with Hyaluronic Acid: Antifungal Activity in a Murine Model of Vulvovaginal Candidiasis","authors":"Aniely Dos Reis Teixeira,&nbsp;Amanda De Vasconcelos Quaresma,&nbsp;Renata Tupinambá Branquinho,&nbsp;Patrícia Capelari De Oliveira,&nbsp;Jorge Andrés García Suárez,&nbsp;Geraldo Célio Brandão,&nbsp;Ana Paula Moreira Barboza,&nbsp;Marcelo Gonzaga De Freitas Araújo,&nbsp;Juliana Teixeira De Magalhães,&nbsp;Sandra Aparecida Lima De Moura,&nbsp;Gisele Rodrigues Da Silva","doi":"10.1208/s12249-025-03081-z","DOIUrl":"10.1208/s12249-025-03081-z","url":null,"abstract":"<div><p>Brazilian green propolis extract-loaded poly(ε-caprolactone) nanoparticles coated with hyaluronic acid (PE-NPsHA) were developed as a therapeutic strategy to treat vulvovaginal candidiasis (VVC) and combat the growing issue of fungal resistance. The chemical composition of PE was analyzed using UHPLC-MS/MS, revealing the presence of various bioactive compounds, such as phenolic acids, flavonoids, coumarins, and quinones. These compounds were encapsulated into the polymeric matrix of NPs, as indicated by FTIR and DSC. In addition, PE-NPsHA were characterized by DLS, AFM, encapsulation efficiency (EE), and <i>in vitro</i> release study. They displayed a spherical morphology with a hydrodynamic diameter of 170 nm, a low polydispersity index of 0.1, a zeta potential of -28.5 mV, and an EE of 78%. The <i>in vitro</i> release study indicated a controlled and sustained release of PE over a period of 96 h. The <i>in vitro</i> and <i>in vivo</i> PE-NPsHA biocompatibility were investigated as well as their antifungal activity in a murine model of VVC. PE-NPsHA did not impact the HaCaT cell viability and demonstrated no signs of <i>in vivo</i> vaginal toxicity. PE-NPsHA exhibited <i>in vivo</i> antifungal efficacy, effectively eliminating <i>Candida albicans</i> infection. PE-NPsHA could expand the available treatment options for VVC and counteract <i>Candida</i> resistance to antifungal drugs.</p></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143621792","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":"Unraveling the Effects of Filtration, Process Interruptions, and Post-Process Agitation on Protein Aggregation","authors":"Christina Winter,&nbsp;Anna Springer,&nbsp;Jean-Loup Descamps,&nbsp;Joris Hoefinghoff,&nbsp;Salehi Mohammad-Sadegh,&nbsp;Amrit Paudel,&nbsp;Milica Stankovic-Brandl","doi":"10.1208/s12249-025-03076-w","DOIUrl":"10.1208/s12249-025-03076-w","url":null,"abstract":"<div><p>Filtration is an essential process step for the manufacturing and filling of biopharmaceuticals. In filling operations, sterile filtration is typically achieved through dead-end filtration using fine membrane filters that completely retain colony-forming units per square centimeter of filter area. According to FDA and USP guidelines, sterilizing filters must be product-compatible and composed of non-fiber releasing materials, typically with a absolute pore size rating of 0.22 µm. However, it has been observed that protein interaction with filters and particle shedding from filter materials, can contribute to protein aggregation when exposed to routine stresses such as agitation during manufacturing, handling, storage or transportation. Since aggregates can cause severe immune responses upon parenteral application, it is crucial to understand the possible effects of various filter materials during different manufacturing and filling set-ups in order to choose the most suitable filter types and filtration processes. To address this, we investigated particle formation on the visible, subvisible and submicron scales as well as structural changes in a specific liquid glycoprotein (GP) formulation after constant and impulse filtration (i.e., stop and go mechanisms to assess possible film formation and film disruption on the filter material) with commonly used hydrophilic membrane materials, i.e., polyvinylidene fluoride (PVDF), polyether sulfone (PES), and cellulose acetate (CA) with a pore size of 0.22 μm. In addition, we exposed the material to stirring and heating to induce aggregation and investigate the filter performances in the case of initially high particle content.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143621793","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":"Characterizing the Complex Multi-Step Degradation Kinetics of Amphotericin B in a Microemulsified Drug Delivery System","authors":"Sarah R. A. Santos,&nbsp;Éverton N. Alencar,&nbsp;Silvana C. C. Urtiga,&nbsp;Wógenes N. Oliveira,&nbsp;Júlio Abreu Miranda,&nbsp;Lucas Amaral-Machado,&nbsp;Francine J. Azeredo,&nbsp;Lee E. Kirsch,&nbsp;Eryvaldo Sócrates T. Egito","doi":"10.1208/s12249-025-03080-0","DOIUrl":"10.1208/s12249-025-03080-0","url":null,"abstract":"<p>Amphotericin B (AmB), a potent amphiphilic drug with antifungal and antileishmanial properties, exhibits reduced nephrotoxicity when delivered via lipid-based systems like microemulsions (ME). However, the complexity of these multi-phasic systems challenges the use of simple schemes and models for describing AmB degradation. The aim of this study was to establish a degradation scheme and model for AmB within a ME, alongside a control micellar formulation. AmB degradation pathways and models in both lipidic and aqueous systems were evaluated based on prior research. Experimental investigations into interface degradation pathways were conducted using a micellar approach. High-Performance Liquid Chromatography (HPLC) was employed for AmB quantification. Oxidation emerges as the principal degradation pathway within micelles, dependent on surfactant-induced aggregation. Considering AmB's behavior in distinct media (lipidic, aqueous, and micellar), an empirical degradation scheme is proposed, translated into a complex multi-pathway mathematical model capable of describing experimental data on AmB degradation in ME under dark conditions. Aggregation and oxidation played significant roles, and kinetic constants were calculated for AmB in ME. The model presented here represents a significant step toward accurately describing the non-linear degradation of AmB in prospective liquid lipid-based dispersions, potentially advancing its market prospects.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602419","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":"Towards Enhanced Solubility of Cannabidiol: Preparation and Evaluation of Cannabidiol Solid Dispersions Using Vacuum Compression Molding","authors":"Achref Cherif,&nbsp;Janhavi Deshmukh,&nbsp;Kavish Sanil,&nbsp;Iman Taha,&nbsp;Daniel Treffer,&nbsp;Eman A. Ashour","doi":"10.1208/s12249-025-03078-8","DOIUrl":"10.1208/s12249-025-03078-8","url":null,"abstract":"<div><p>The present study aims to develop and characterize cannabidiol (CBD) solid dispersions using Vacuum Compression Molding (VCM) to enhance the drug solubility and release profile. Solid dispersions of CBD and polymers were processed using VCM at 130 °C for 4 min after a prior physical mixing. Five percent w/w of CBD was used with 5% w/w of poloxamer 188 and 90% w/w of polymeric carrier (Polyethylene Oxide, PEO-N80 or Hydroxypropyl cellulose, HPCEF). Discs were collected and milled to obtain formulations (F1V, F2V). The degradation temperature of CBD was determined using Thermogravimetric Analysis (TGA). The formulations were further characterized using differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and Fourier-Transform Infrared Spectroscopy (FTIR). <i>In vitro</i> dissolution testing of pure CBD and formulations was evaluated using USP apparatus II. TGA showed that CBD degradation occurs after 200 °C. FTIR spectra of formulations indicate potential interactions between the drug and polymers. DSC thermograms of F1V showed a thermal peak at 65 °C that could correspond to PEO-N80. F2V did not show any of the thermal event peaks, which suggests the conversion of the drug to the amorphous state. Images from the SEM showed irregular surfaces for both formulations. The release profile showed an increase in the CBD dissolution rate by 4.75 folds for F1V and 3.63 folds for F2V in four hours. In this study, solid dispersions of CBD formulations were successfully achieved. The VCM technology has proven to be successful in formulating solid dispersions of CBD for early-stage drug development.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03078-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143594723","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":"Eudragit S 100 Assisted Molecular Solid Dispersion of Andrographolide Tendered Augmented Drug Delivery and Apoptosis in Human Colon Cancer, HT-29 Cells","authors":"Pawan Devangan,&nbsp;Anamika Sharma,&nbsp;Nitin Wadate,&nbsp;Atul Mourya,&nbsp;Jitender Madan","doi":"10.1208/s12249-025-03073-z","DOIUrl":"10.1208/s12249-025-03073-z","url":null,"abstract":"<div><p>Colorectal cancer is the second most common cause of death due to growing incidence. Andrographolide (AGD) induces apoptosis in colorectal cancer cells; however, oral administration of AGD is associated with hindered aqueous solubility (3.29 ± 0.73-μg.mL⁻¹) and bioavailability of 15.87 ± 3.84%. Therefore, in the current investigation, AGD was amalgamated with Eudragit S100 (EUS100) to engineer a molecular amorphous solid dispersion (EUSD). EUSD4, an optimized molecular solid dispersion showed ~ 5.90 and ~ 7.14-fold augmentations in solubility at pH ~ 6.8 and ~ 7.4, respectively as compared to AGD alone. The% assay and drug loading were respectively measured to be 96.01 ± 3.52% and 19.85 ± 0.65%. ATR and ¹H-NMR spectroscopies confirmed that the -OH group of AGD formed an intermolecular hydrogen bond with the –C = O of EUS100. Moreover, a hallo pattern of PXRD, the disappearing of an endothermic peak in DSC, the absence of a birefringence pattern under polarized light, and disorders in the initial particle shape confirmed the amorphous state of EUSD4. In addition, a ~ 4.70- and ~ 2.94-fold enhancement in dissolution profile in simulated intestinal fluid (SIF, pH ~ 6.8) and simulated colonic fluid (SCF,pH ~ 7.4) of EUSD4 suggested amendment in the hydrophilicity, wettability properties, and dissolution rate. Furthermore, the IC50 of EUSD4 was ~ 1.42-fold higher than AGD, indicating improvement in anticancer efficacy against HT-29 cells. EUSD4 exhibited superior cytotoxicity over AGD owing to the induction of apoptotic cell death, mitochondrial membrane loss (ΔΨm), remarkable S-G2/M phase cell-cycle arrest and enhanced ROS generation in HT-29 cells. In conclusion, EUSD4 warrants further <i>in-vivo</i> antitumor testing under a set of stringent parameters against colorectal cancer.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143594693","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}