AAPS PharmSciTech最新文献

{"title":"Mupirocin-Doped α-Cellulose Nanopaper for Wound Dressing: Development, In Vitro Characterization and Antimicrobial Studies","authors":"Nivedita Pant,&nbsp;Sarika Wairkar","doi":"10.1208/s12249-024-03013-3","DOIUrl":"10.1208/s12249-024-03013-3","url":null,"abstract":"<div><p>This research aimed to develop a mupirocin-doped α-cellulose nanopaper (MDAC-NP) as a wound dressing to accelerate wound healing while limiting localized bacterial growth. The α-cellulose nanofibrils suspension was prepared by ultrasonication followed by microfluidization and subsequently doped with 0.05% w/v mupirocin to prepare nanopaper (MDAC-NP-A). The optimized batch of MDAC-NP had a porosity of 47.46 ± 0.60%, a thickness of 30 μm and a tensile strength of 0.113 MPa. The transmission electron microscopy images revealed long, slender, intertwined nanofibrillar structures and the scanning electron microscopy confirmed stable lamellar structures with tight nanofibrillar networks, giving them translucency. MDAC-NP-A had an excellent water vapor transmission rate of 2963 ± 10.26 g/m²/day, providing an optimal moist environment locally to promote wound healing. The mupirocin inclusion in the nanopapers was corroborated by the Fourier transform infrared spectroscopy and its crystallinity by X-ray diffraction, and differential scanning calorimetry results. The 100% drug release, was observed at 12 h from optimized MDAC-NP-A with a controlled release pattern. The MDAC-NP showed better antimicrobial activity, against <i>S. aureus</i> (41 mm) than <i>E. coli</i> (25 mm) and <i>P. aeruginosa</i> (17 mm) and was found to be better than marketed ointment. Thus, mupirocin-doped α-cellulose nanopapers emerge as a potential wound dressing for treating primary and secondary skin infections caused by external wounds.</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 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811182","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":"Mesogenic Architectures for Advanced Drug Delivery: Interrogating Lyotropic and Thermotropic Liquid Crystals","authors":"Induja Govindan,&nbsp;Angeeta Paul,&nbsp;Annamalai Rama,&nbsp;Anjana A. Kailas,&nbsp;K. A. Abutwaibe,&nbsp;Thamizharasan Annadurai,&nbsp;Anup Naha","doi":"10.1208/s12249-024-02985-6","DOIUrl":"10.1208/s12249-024-02985-6","url":null,"abstract":"<div><p>The possibility of precisely regulating and targeting drug release with mesophase or Liquid crystal drug delivery systems has drawn much attention recently. This review offers a thorough investigation of liquid crystal drug delivery systems with an emphasis on their mesogenic architecture. It describes the various liquid crystal forms such as thermotropic and lyotropic liquid crystals and their applicability in advanced drug delivery. Liquid crystals are used as excellent carriers due to their distinctive characteristics, such as stimuli-responsive drug delivery and sustained release patterns. Comprehending the materials that form mesophase provides insight into their distinct physiochemical characteristics and their use in drug delivery. This review highlights the important role lyotropic and thermotropic liquid crystals play in drug delivery, underscoring their considerable potential. The transition of thermotropic liquid crystals from their conventional technological applications to drug delivery has been studied. Nonetheless, a few challenges still need to be addressed, including formulation strategy refinement, regulating release rates, maximising the loading of hydrophilic drugs, and storage stability. In the pharmaceutical field, addressing these issues will open the door to a revolutionary paradigm that will revolutionise therapeutic outcomes and improve patient care.</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 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-024-02985-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142778577","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":"Impact of Storage on In Vitro Permeation and Mucoadhesion Setup Experiments Using Swine Nasal Mucosa","authors":"Jaiza Samara Macena de Araújo,&nbsp;Gabriela Gama Xavier Augusto,&nbsp;Aylla Mesquita Pestana,&nbsp;Francisco Carlos Groppo,&nbsp;Flávia Sammartino Mariano Rodrigues,&nbsp;Pedro Duarte Novaes,&nbsp;Michelle Franz-Montan","doi":"10.1208/s12249-024-03002-6","DOIUrl":"10.1208/s12249-024-03002-6","url":null,"abstract":"<div><p>Intranasal topical administration offers a promising route for local and systemic drug delivery, with <i>in vitro</i> permeation and mucoadhesion studies often using porcine models. However, the impact of storage on mucosal integrity after the procedure remains unaddressed. This study aimed to standardize the preparation process and evaluated whether storage of porcine nasal mucosa impairs its integrity and permeability for experimental comparisons. Additionally, an optimized <i>in vitro</i> mucoadhesion experiment using texture analyzer equipment was investigated. Porcine nasal mucosa was subjected to different storage conditions (\"fresh\"; refrigerated at 4°C for 24 h and 48 h, and frozen at -20°C for two or three weeks) and assessed using optical and transmission electron microscopy. <i>In vitro</i> permeation assays were performed in a Franz-type vertical diffusion system with lidocaine hydrochloride (LDC). <i>In vitro</i> mucoadhesion assays were conducted using fresh nasal mucosa and a commercial nasal topical formulation using TA.XT. Plus texture analyzer. The variables involved (probe speed, contact time, and application force) in assessing mucoadhesive capacity (maximum mucoadhesive force F_max and work of mucoadhesion W_muc) were optimized using a Central Composite Design. Fresh tissues showed no alterations in histological arrangement or in the ultrastructure of adherence junctions. Stored tissues exhibited histological disorganization, reduced thickness, and loss of epithelial integrity. LDC permeability increased in storage tissues (<i>p</i> &lt; 0.05). Contact force had a positive effect on F_max and W_muc (<i>p</i> &lt; 0.0001), with a minimum required value of 0.48 N. Variations in contact time and probe speed did not affect the responses (<i>p</i> &gt; 0.05). In conclusion, the preparation technique was adequate to maintain mucosa integrity for permeability studies. However, storing the mucosa at 4 or -20°C overestimated LDC permeation, which could mislead critical data for formulation development. Therefore, the use of fresh mucosa is recommended to ensure more reliable results. For <i>in vitro</i> mucoadhesion assays, a minimum contact force of 0.48N is required for optimal responses.</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 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142778377","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":"Pharmacokinetic Prediction of Immediate- and Extended-Release Tablets for Patients with Liver Disease Using Whole Body Physiologically-Based Pharmacokinetic Modeling for the Antipsychotic Drug Quetiapine","authors":"Ji-Hun Jang,&nbsp;Seung-Hyun Jeong","doi":"10.1208/s12249-024-02995-4","DOIUrl":"10.1208/s12249-024-02995-4","url":null,"abstract":"<div><p>Although quetiapine metabolism occurs extensively in the liver and careful dosing is recommended in patients with liver disease, there has been a paucity of pharmacometric studies to adjust the clinical dose of quetiapine according to liver-disease severity. This study aimed to establish a whole-body, physiologically-based pharmacokinetic (WB-PBPK) model to explain interindividual variability in quetiapine <i>PK</i> and quantitatively predict <i>PK</i> in patients with liver disease. The developed WB-PBPK model well described the PK characteristics of different quetiapine regimens in healthy populations. The PK predictions could also be applied to patients with schizophrenia (without significant differences from healthy subjects). For the same total dose of quetiapine, both immediate-release (IR) and extended-release (ER) tablets showed significantly increased exposure and decreased clearance in patients with liver disease compared to healthy subjects. The model showed that steady-state plasma quetiapine concentrations exceeded the usual therapeutic range after multiple doses of IR tablets 250 mg three times daily or ER tablets 800 mg once daily in patients with liver disease. Therefore, the doses of quetiapine IR or ER tablets could be reduced by 0.10–0.50 times depending on liver-disease severity, so that mean steady-state plasma concentrations could be positioned near the therapeutic range. WB-PBPK modeling for quetiapine enabled quantitative prediction of <i>PK</i> according to IR or ER formulation and liver-disease severity. The results of this study provide useful data for improving the therapeutic use of quetiapine by enabling dose selection based on formulation and liver-disease severity.</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 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142778580","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":"Isoquercitrin Loaded PEGylated Long Circulating Liposomes Improve Bone Mass and Reduce Oxidative Stress After Osteoporosis","authors":"Liangju Sheng,&nbsp;Fuping Gao,&nbsp;Zhe Lan,&nbsp;Bin Zong,&nbsp;Qilong Wang","doi":"10.1208/s12249-024-02993-6","DOIUrl":"10.1208/s12249-024-02993-6","url":null,"abstract":"<div><p>Osteoporosis has increasingly become a major public health concern because of its associated heightened risk of bone fragility and fractures. In order to avoid the adverse risk of hormone therapy, scientists have considered isoquercitrin (IQ) as a natural phytoestrogen to potentially prevent osteoporosis. However, IQ has poor solubility and bioavailability which culminates in rapid elimination of phytoestrogen. Herein, this study sought to solve limited applications of IQ by preparing IQ-loaded PEGylated long circulating liposomes (IQ-Lips) via thin-film hydration method. After appropriate characterization using zeta-potential, polydispersed index (PDI), particle size and entrapment efficiency (EE), IQ-Lips were applied to ovariectomized rat models to evaluate their effect on osteoporosis. The results showed that the prepared IQ-Lips exhibited smaller sized nanoparticles (125.35 ± 4.50 nm), excellent PDI (0.244 ± 0.001) and zeta-potential (-28.64 ± 0.71 mV) with stable property and higher EE (92.10 ± 0.32%). Importantly, administration of IQ-Lips through oral route increased aqueous solvability, bioavailability and circulation time of IQ. Moreover, the IQ-Lips could increase bone microstructural densities and bone mass, as well as reduce oxidative stress in ovariectomized rat models. Altogether, the IQ-Lips may serve as a novel avenue to potentially prolong the circulation of IQ in the body and improve the bioavailability of IQ for treatment of osteoporosis.</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 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142778579","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":"Investigation of Minipigs as the Optimal Non-rodent Pre-clinical Species: Exploring Plasma Protein Binding of Marketed Cardiovascular Drugs Across Species","authors":"Subodh Mondal,&nbsp;Ritika Uppal,&nbsp;Satish CS","doi":"10.1208/s12249-024-03005-3","DOIUrl":"10.1208/s12249-024-03005-3","url":null,"abstract":"<div><p>Pre-clinical studies in animals are an essential part of drug development for new chemical entities. Before clinical trials in humans, submission of safety data from one rodent and one non-rodent species is compulsory as per regulatory guidelines. Even though minipigs and monkeys are physiologically closer to humans, dogs are usually employed as the non-rodent pre-clinical species. In this study, the <i>in vitro</i> plasma protein binding of eleven marketed cardiovascular drugs was studied in dog, minipig, monkey and human to determine the preferred species. To conduct plasma protein binding studies, the most reliable equilibrium dialysis method was adopted. Ten out of eleven tested cardiovascular drugs showed statistically similar plasma protein binding in minipig and human plasma which was different from dog and monkey plasma. The results from the studies showed greater similarity between minipigs and humans suggesting that the minipig species maybe a better pre-clinical non-rodent model during drug development of cardiovascular drugs instead of the conventional dog species. Additionally, use of the more accessible minipig species may help in saving time, and resources during pre-clinical studies and may also be more predictive during the safety studies in humans during later stage clinical trials.</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 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-024-03005-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142778576","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":"Cyclodextrin Drugs in Liposomes: Preparation and Application of Anticancer Drug Carriers","authors":"Lanni Feng,&nbsp;Ruting Wei,&nbsp;Jiali Wu,&nbsp;Xinmei Chen,&nbsp;Yan Wen,&nbsp;Jianming Chen","doi":"10.1208/s12249-024-02999-0","DOIUrl":"10.1208/s12249-024-02999-0","url":null,"abstract":"<div><p>Cyclodextrin complexes have been widely used in pharmaceutical applications, but disadvantages such as the rapid clearance of cyclodextrins from the blood stream after <i>in vivo</i> administration or their replacement by other molecules in the biological medium with higher luminal affinity for cyclodextrins limit the application of cyclodextrins as drug carriers. Liposome-encapsulated hydrophobic drugs have low and unstable drug loading rates. Drug-in-CD-in-liposome (DCL), which encapsulate cyclodextrin inclusion complexes into liposomes, combine the advantages of both delivery systems, can effectively avoid the leakage and rapid release of lipophilic drugs in the lipid bilayer, and help to maintain the integrity of liposomes. This paper focuses on the preparation method, characterization and application of DCL, with a view to providing methods and references for the research and application of DCL technology.</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 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142778396","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":"A Novel Self-Assembled Paclitaxel Nanodispersion Facilitates Rapid In-Vitro/In-Vivo Dissociation and Protein Binding","authors":"Ajay J. Khopade,&nbsp;Malay D. Shah,&nbsp;Bhushan Borole","doi":"10.1208/s12249-024-02996-3","DOIUrl":"10.1208/s12249-024-02996-3","url":null,"abstract":"<div><p>The study aims to prepare and characterize a novel paclitaxel (PtX) preconcentrate formulation using polymer and lipid excipients that forms nanodispersion upon dilution. The goal was to understand the mechanism of nanodispersion formation and its properties. The water-insoluble PtX was dissolved in organic solvents containing ethanol, polyethylene glycol (PEG400), povidone (PVP), caprylic acid (CA), and sodium cholesterol sulfate (CS). This formulation was diluted in 5% w/v dextrose medium to form PtX nanodispersion, which was assessed for particle size, stability, <i>in-vitro</i>/<i>in-vivo</i> dissociation and protein binding. Transmission electron microscopy (TEM), Small Angle Neutron Scattering (SANS), and Molecular Dynamics (MD) simulations were used to analyse the structure of the nanoparticles. The formulation was a clear, slightly yellow solution. The PtX nanodispersion displays particle size of ~ 100 nm with a zeta potential of -25, and the pH of 4.0. It displayed nearly spherical coacervate nanoparticles with a sponge-like structure, lacking internal structure order as revealed by TEM and SANS. MD simulations confirmed self-assembly of PtX and excipients forming nanoparticles. <i>In vitro</i> dissociation studies in simulated plasma demonstrated rapid dissociation of nanodispersion, releasing free PtX that immediately binds to plasma proteins. <i>In vivo</i> studies in rabbits corroborated these findings, showing rapid dissolution. The results present a novel formulation design that forms sponge-like coacervate nanoparticle due to complimentary interactions of the excipients that otherwise are unable to self-assemble under similar conditions of dilution. This alternative formulation solves the limitations of currently marketed PtX products and can provide its effective delivery in clinical settings.</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 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142778578","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":"Bifunctional Oxaliplatin (IV) Prodrug Based pH-Sensitive PEGylated Liposomes for Synergistic Anticancer Action Against Triple Negative Breast cancer","authors":"Lavkesh Bhute,&nbsp;Sayali Dighe,&nbsp;Oly Katari,&nbsp;Vivek Yadav,&nbsp;Sanyog Jain","doi":"10.1208/s12249-024-02988-3","DOIUrl":"10.1208/s12249-024-02988-3","url":null,"abstract":"<div><p>Triple negative breast cancer (TNBC) exhibits higher susceptibility towards oxaliplatin (OXA) due to a faulty DNA damage repair system. However, the unfavorable physicochemical properties and risk of toxicities limit the clinical utility of OXA. Therefore, to impart kinetic inertness, site-specific delivery, and multidrug action, an octahedral Pt(IV) prodrug was developed by using chlorambucil (CBL) as a choice of ligand. The combination of OXA and CBL exhibited synergistic anti-cancer action in TNBC cell lines. Further, to maximize tumor-specific delivery, intracellular accumulation, and <i>in-vivo</i> performance, the developed prodrug (OXA-CBL) was encapsulated in pH-sensitive PEGylated liposomes into (OXA-CBL/PEG-Liposomes). The fabricated liposomes had smaller particle size &lt; 200 nm and higher drug loading (~ 4.26 ± 0.18%). <i>In-vitro</i> release displayed pH-dependent sustained release for up to 48 h. Cellular internalization revealed maximal uptake via clathrin-mediated endocytosis. The cytotoxicity assay showed reduced IC₅₀ in the 4T1 (~ 1.559-fold) and MDA-MB-231 (~ 1.539-fold) cell lines than free OXA-CBL. <i>In-vivo</i> efficacy in 4T1-induced TNBC model revealed a marked increase in % tumor inhibition rate, while diminished % tumor burden in OXA-CBL/BSA-NPs treated animals. Toxicity assessment displayed no signs of systemic and hemolytic toxicity. Overall, delivery of Pt (IV) prodrug as a pH-sensitive PEGylated liposomes offers a safer and efficient system to manage TNBC.</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 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142778183","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":"Physiologically Based Biopharmaceutics Modeling Coupled with Biopredictive Dissolution in Development of Bioequivalent Formulation for Mesalamine Enteric Coated Tablet: A Tough Nut to Crack","authors":"Sivacharan Kollipara,&nbsp;Pankaj Kumar Prabhat,&nbsp;Paramita Saha,&nbsp;Saurabh Gupta,&nbsp;Venkat Ramana Naidu,&nbsp;Tausif Ahmed","doi":"10.1208/s12249-024-02990-9","DOIUrl":"10.1208/s12249-024-02990-9","url":null,"abstract":"<div><p>Mesalamine is a locally acting anti-inflammatory drug used to treat mild to moderate ulcerative colitis. Because of complex formulation principle and high <i>in vivo</i> variability, development of bioequivalent formulation for mesalamine is challenging. Further, fed state possess significant challenges for bioequivalence (BE) due to interplay of multiple factors. In the work, we have developed a novel biopredictive media for mesalamine enteric coated tablets and integrated into physiologically based biopharmaceutics model (PBBM) to predict <i>in vivo</i> fed behavior. USP III based gradient media was developed to mimic <i>in vivo</i> fed condition. The developed PBBM was initially validated with literature data and subsequently re-optimized with pilot BE study data. Further, virtual bioequivalence (VBE) was performed to evaluate model predictability for pilot BE data. Later, the model was applied for prospective BE predictions with increased subjects and parametric sensitivity analysis was performed to identify physiological factors that can impact <i>in vivo</i> performance. Further, the model was used to predict luminal and enterocyte concentrations in colon to demonstrate equivalent efficacy. Additionally, a novel dissolution/permeation tool (Dissoflux) was employed to compare permeability behavior of formulations. Overall, this work enabled BE prediction for complex mesalamine enteric coated tablets and helped to understand parameters that can impact <i>in vivo</i> performance.</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 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142761957","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}