Drug metabolism and bioanalysis最新文献

{"title":"Emerging Trends in Ophthalmic Drug Delivery: Focus on NSAIDs and Corticosteroids.","authors":"Sheetal Devi, Vipin Saini, Manish Kumar, Navneet Mehan, Dushyant, Smita Narwal, Ashwani K Dhingra, Gurvirender Singh","doi":"10.2174/0131173853470970260930074014","DOIUrl":"https://doi.org/10.2174/0131173853470970260930074014","url":null,"abstract":"<p><p>Ocular drug delivery is severely affected by anatomical and physiological ocular barriers, preventing drug permeation and therapeutic effects. Uveitis, keratitis, and inflammatory postoperative ocular complications demand accurate, sustained, and localized therapy. Nonsteroidal Anti-inflammatory Drugs (NSAIDs) and Steroidal Anti-inflammatory Drugs (Corticosteroids) are cornerstones for managing anterior and posterior ocular inflammation. Their traditional formulations, however, are flawed, with compromised bioavailability, tear clearance, and systemic toxicity. Nano-formulations prepared using the latest breakthroughs in nanotechnology have transformed ophthalmic drug delivery by offering enhanced solubility, prolonged retention time, and extended drug release. Liposomes, nanoemulsions, dendrimers, and polymeric nanoparticle-based nanocarriers enhance the therapeutic index of Corticosteroids and NSAIDs by improving penetration across ocular barriers and reducing dosing intervals at the systemic level. Of particular interest, prodrug medications, such as nepafenac, are metabolized intraocularly and provide greater inhibition of cyclooxygenase-2 (COX-2). To this end, biopharmaceutical drug evaluation tools, e.g., in vitro models of the cornea, pharmacokinetic profiling, and ocular imaging, are of utmost significance for determining the drug's efficacy and safety. Immunopharmacology, by the design of immunosuppressive drugs such as cyclosporine A, is also another branch of anti-inflammatory therapies, such as for chronic ocular surface diseases, such as dry eye. Nano-based and combination corticosteroids have been effective methods for controlled inflammation and synergy. Together with nanotechnology and the incorporation of biopharmaceutical screening, the era is opening to a new generation of ophthalmic anti-inflammatory therapy with lower risk, greater efficacy, and a patient-centered approach.</p>","PeriodicalId":521353,"journal":{"name":"Drug metabolism and bioanalysis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response Surface Methodology-driven RP-HPLC-PDA Approach to Analytical Method Development, Validation, and Quantitation of Ixazomib in its Pharmaceutical Formulations.","authors":"Aradhana Panigrahy, Pratap Kumar Patra, Bikash Ranjan Jena, Himansu Bhusan Samal, Surya Kanta Swain","doi":"10.2174/0131173853504893260910071717","DOIUrl":"https://doi.org/10.2174/0131173853504893260910071717","url":null,"abstract":"<p><strong>Introduction: </strong>The second most common malignancy in adults that impairs immune function is multiple myeloma. For the treatment of this kind of cancer, Ixazomib is one of the second-generation medications used. It is a reversible oral proteasome inhibitor.</p><p><strong>Method: </strong>A response surface approach using the RP-HPLC method was established to analyze the drug. A Waters Alliance 2695e RP-HPLC unit with a 2998 PDA detector and a Zorbax SB C18 Analytical column (75˟4.6mm˟5μm particle size) was used for the study. The study was conducted at 215 nm to separate the drug. A total of 13 runs were suggested by the CCD experimental design and were conducted to optimize the method. Using an arithmetic model, the effects of dependent variables on the responses were examined.</p><p><strong>Results: </strong>The ideal experimental conditions for the proposed study include a mobile phase comprising acetonitrile and an aqueous solution of glacial acetic acid and sodium salt of 1- hexanesulfonic acid (30:70% v/v). Over the concentration range of 25-750 μg/mL, a linear calibration curve was obtained. Recoveries ranged from 99% to 101% across three concentrations.</p><p><strong>Discussion: </strong>The Design Expert version 13 software was used to conduct the statistical evaluation of the runs. The analysis suggests that the most significant parameters influencing the intended responses were column temperature and flow rate, as indicated by the 3D response surface curves.</p><p><strong>Conclusion: </strong>The developed method demonstrated remarkable results across different analyses within the limits of estimation for Ixazomib. Forced degradation studies and solution stability studies also confirmed the drug's stability. This indicates that the suggested method could be a valuable technique for the precise and accurate estimation of Ixazomib.</p>","PeriodicalId":521353,"journal":{"name":"Drug metabolism and bioanalysis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting Cinacalcet HCl Hepatic Disposition: Insights from Isolated Perfused Rat Liver.","authors":"Katayoon Mireskandari, Ahmadreza Barazesh, Mostafa Rostamnezhad, Majid Darabi, Hoda Lavasani, Mohammadreza Rouini","doi":"10.2174/0131173853473593260918121024","DOIUrl":"https://doi.org/10.2174/0131173853473593260918121024","url":null,"abstract":"<p><strong>Introduction: </strong>Hepatic drug handling determines systemic exposure, yet the balance between tissue uptake, intracellular binding, and metabolic clearance is difficult to dissect in vivo. Cinacalcet hydrochloride (CINA), a calcimimetic used to manage secondary hyperparathyroidism, has low oral bioavailability and is widely described as a high-extraction drug subject to extensive hepatic metabolism. Whether tissue sequestration rather than biotransformation underlies its rapid hepatic removal has not been tested directly in an intact ex vivo liver model.</p><p><strong>Methods: </strong>We investigated the hepatic clearance of cinacalcet hydrochloride (CINA) using the isolated perfused rat liver (IPRL) model. A validated high-performance liquid chromatography (HPLC) method was established to quantify CINA and its primary metabolite, M7, in both liver tissue and perfusate samples. To evaluate the influence of perfusate composition and protein binding, experiments were conducted under single-pass perfusion modes, in the presence and absence of bovine serum albumin (BSA).</p><p><strong>Results: </strong>Dose recovery and mass balance analysis indicated that ~93% of the administered dose was recovered: ~63% in liver tissue and ~29% in the outlet perfusate. No metabolites were detected in any sample, pointing to tissue uptake and retention as the dominant clearance mechanism. Drug loss to plastic perfusion tubing was substantial and was only partially offset by BSA. Inclusion of BSA also shifted the apparent drug distribution between liver and perfusate.</p><p><strong>Discussion: </strong>In the IPRL, hepatic tissue sequestration rather than metabolic conversion was the dominant clearance mechanism for CINA. Non-specific adsorption to plastic perfusion tubing and the protein content of the perfusion medium were important confounders that must be controlled in future ex vivo studies.</p><p><strong>Conclusion: </strong>CINA was extensively retained in rat liver tissue with negligible in situ metabolism over 90 min of single-pass perfusion, raising the question of whether metabolic extraction truly explains its low oral bioavailability in vivo.</p>","PeriodicalId":521353,"journal":{"name":"Drug metabolism and bioanalysis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging Piperazine Derivatives: Synthesis, Characterization, Biological Evaluation, Molecular Docking, and ADMET In silico Studies.","authors":"Renu Verma, Ankur Yadav, Nitin Kumar, Uma Agarwal, Vijay Kumar Sharma","doi":"10.2174/0118723128439196260603153133","DOIUrl":"https://doi.org/10.2174/0118723128439196260603153133","url":null,"abstract":"<p><strong>Introduction: </strong>Antimicrobial resistance (AMR) is a major global concern, with pathogens such as E. coli, B. subtilis, P. aeruginosa, and S. aureus showing increasing resistance to conventional antibiotics. Piperazine, a six-membered heterocyclic scaffold, is widely used in drug design due to its flexibility and diverse biological activities.</p><p><strong>Methods: </strong>A new series of piperazine derivatives was synthesized with aromatic and heterocyclic substituents. The compounds were characterized using spectroscopic and physicochemical techniques. Their antibacterial activity was evaluated in vitro against Gram-positive and Gram-negative bacteria using the cup-plate method, with ciprofloxacin employed as the standard reference drug. Molecular docking studies and in silico ADME/Tox analyses were performed to assess protein binding, pharmacokinetic properties, and toxicity. Based on the results, a structure-activity relationship (SAR) analysis was also carried out.</p><p><strong>Results: </strong>Among the synthesized derivatives, compound 13 exhibited the most potent broad-spectrum antibacterial activity, showing maximum inhibition against Bacillus subtilis (21.3 mm) along with notable activity against Escherichia coli and Staphylococcus aureus. Molecular docking studies revealed strong binding affinity toward DHFR from S. aureus (-10.60 kcal/mol) and ankyrin repeat protein from B. subtilis (-9.02 kcal/mol). Additionally, in silico ADME/Tox predictions suggested favorable oral bioavailability, low toxicity risk, and minimal inhibition of CYP enzymes. The SAR analysis showed that piperazine derivatives containing well-placed electron-withdrawing groups and balanced physicochemical properties displayed improved antibacterial activity, with compound 13 emerging as the most potent due to its strong molecular interactions.</p><p><strong>Discussion: </strong>SAR analysis indicated that electron-withdrawing substituents on the piperazine core enhanced antibacterial potency. The combination of structural modification, strong protein binding, and favorable pharmacokinetic properties explains the superior activity of compound 13.</p><p><strong>Conclusion: </strong>Compound 13 emerges as a promising broad-spectrum antibacterial agent. The study demonstrates the potential of SAR-guided piperazine derivatives for developing novel antibacterial therapeutics and supports further in vivo evaluation and structural optimization.</p>","PeriodicalId":521353,"journal":{"name":"Drug metabolism and bioanalysis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Green and Robust RP-HPLC for Simultaneous Quantification of Gallic, Ferulic, and Caffeic Acids in Human Plasma via Box-Behnken Design-Based Optimization.","authors":"Lalitha Repudi, Mohana Vamsi Nuli, Pavan Kumar Jaini, Ramanjaneyulu Seemaladinne, Kirankumar Chagarlamudi, Kumaraswamy Gandla","doi":"10.2174/0118723128455332260605064308","DOIUrl":"https://doi.org/10.2174/0118723128455332260605064308","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to develop and validate a sustainable reversed-phase high-performance liquid chromatography (RP-HPLC) method for the simultaneous quantification of Gallic Acid (GA), Ferulic Acid (FA), and Caffeic Acid (CA) in human plasma, aligning with green analytical chemistry principles and regulatory guidelines.</p><p><strong>Methods: </strong>Chromatographic conditions were optimized using a Box-Behnken design under the framework of response surface methodology, evaluating the influence of acetonitrile concentration, mobile-phase pH, and flow rate on retention time, peak symmetry, and efficiency. Method validation was performed in accordance with ICH M10 and EC 2002/657/EC guidelines, including assessment of linearity, accuracy, precision, recovery, stability, and matrix effects. The environmental impact of the analytical workflow was assessed using ComplexGAPI, AGREE, AGREEprep, Eco-Scale, and BAGI metrics.</p><p><strong>Results: </strong>The optimized chromatographic parameters, 35% acetonitrile, pH 2.8, and a flow rate of 0.6 mL/min, produced well-resolved peaks with retention times of 2.039 min for GA, 3.077 min for FA, and 3.990 min for CA, while yielding minimal deviations (<5%) between predicted and experimental responses. The method demonstrated excellent linearity (R² > 0.999), with limits of detection and quantification ranging from 0.151-1.236 μg/mL and 0.453-3.70 μg/mL, respectively. Accuracy, precision, and recovery were within acceptable regulatory limits. The analytes exhibited robust stability under stress and storage conditions with negligible matrix interference.</p><p><strong>Discussion: </strong>The integration of chemometric optimization and multi-tool environmental evaluation confirmed the method's analytical efficiency and ecological compatibility. Compared with conventional RP-HPLC protocols, the proposed workflow significantly reduces solvent usage and hazardous waste generation while maintaining analytical performance.</p><p><strong>Conclusion: </strong>The developed RP-HPLC method provides a validated, reliable, and environmentally sustainable analytical platform for quantifying phenolic acids in human plasma. Its regulatory compliance, robustness, and reduced ecological footprint make it suitable for routine clinical and pharmacokinetic studies.</p>","PeriodicalId":521353,"journal":{"name":"Drug metabolism and bioanalysis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial Intelligence in LC-MS/MS Data Analysis for Pharmacokinetic Studies Dayananda Sagar University, India.","authors":"Darshan Gowda B S, Yashaswini G, K B Premakumari","doi":"10.2174/0118723128434043260513112516","DOIUrl":"https://doi.org/10.2174/0118723128434043260513112516","url":null,"abstract":"<p><p>Liquid chromatography-tandem mass spectrometry (LC-MS/MS) plays a critical role in pharmacokinetic research by enabling precise quantification of drugs and their metabolites in biological matrices such as blood and tissue samples. Owing to its high sensitivity and accuracy, the technique is extensively employed during drug development and evaluation processes. Beyond simple quantification, LC-MS/MS provides comprehensive insights into drug absorption, distribution, metabolism, and excretion. Recent advancements in computational technologies have significantly transformed the interpretation of LC-MS/MS data. Advanced software systems and machine learning algorithms facilitate the identification of complex patterns that may not be readily detectable through conventional analytical approaches. In addition to improving signal discrimination and reducing analytical noise, these technologies enhance the detection of low-abundance compounds and improve performance when analyzing complex biological samples. Consequently, analytical workflows have become more efficient while maintaining high levels of reliability and reproducibility. Artificial intelligence (AI) and machine learning applications further contribute to pharmacokinetic investigations by predicting drug disposition patterns, identifying metabolic pathways, and assessing potential drug-drug interactions. Compared with traditional analytical methods, AI-driven systems enable rapid data processing, minimize manual intervention, ensure greater consistency, and support compliance with regulatory standards. Recent developments demonstrate that these systems are increasingly capable of recognizing intricate chemical signatures, detecting anomalous findings, and generating more accurate predictive outcomes. Despite these advancements, several challenges remain. Interpretation of complex datasets, validation of algorithmic reliability, and regulatory acceptance continue to limit widespread implementation. Furthermore, emerging innovations such as adaptive analytical workflows, cloud-based laboratory platforms, and integration of pharmacogenomic data with pharmacokinetic studies are beginning to reshape the field. Overall, the integration of AI with LCMS/ MS is advancing pharmacokinetic research by improving analytical precision, streamlining workflows, and enhancing consistency. These developments are expected to support personalized medicine approaches and facilitate more efficient drug development processes. Rather than replacing scientific expertise, artificial intelligence serves as a complementary tool that enhances the accuracy, efficiency, and reliability of pharmaceutical research and drug evaluation.</p>","PeriodicalId":521353,"journal":{"name":"Drug metabolism and bioanalysis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Nano-Emulsion Intranasal Delivery Systems for Neurotherapeutics like Depression.","authors":"Megha Gautam, Nakul Gupta, Sarfaraz Alam, Shreyasi Thakur","doi":"10.2174/0118723128427116260331043534","DOIUrl":"https://doi.org/10.2174/0118723128427116260331043534","url":null,"abstract":"<p><p>Introduction Major Depressive Disorder (MDD) is a prevalent global mental health challenge with a multifactorial etiology, including genetic, environmental, and biochemical influences. Current pharmacological treatments, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), face limitations, including delayed therapeutic onset, systemic side effects, and poor permeability across the blood-brain barrier (BBB). To overcome these challenges, intranasal NE (NE) drug delivery systems have emerged as a promising approach for enhancing drug bioavailability and facilitating direct nose-to-brain transport. Methods A comprehensive review of recent advancements in NE-based drug delivery for MDD was conducted, focusing on formulation strategies, pharmacokinetic improvements, and therapeutic outcomes. Studies evaluating the efficacy of NE formulations for delivering antidepressants, antipsychotics, and natural compounds, such as curcumin and resveratrol, were analyzed. The role of mucoadhesive agents like chitosan in enhancing nasal retention and drug absorption was also explored. Results NE formulations demonstrated superior drug delivery to the CNS, bypassing the BBB and reducing systemic toxicity. Preclinical and clinical studies indicate enhanced therapeutic efficacy, increased drug concentration at target sites, and improved patient compliance. The inclusion of mucoadhesive agents further optimized nasal retention, prolonging drug absorption and enhancing therapeutic effects. Additionally, NEs mitigated hepatic first-pass metabolism, leading to lower dosing requirements and reduced side effects. Discussion Nanoemulsion-based intranasal delivery presents a promising strategy for treating MDD, offering physiological and pharmacological advantages over oral routes. By bypassing the blood-brain barrier, these systems enable rapid and targeted brain delivery, enhancing drug efficacy. The nanoscale size improves solubility and absorption of poorly water-soluble compounds like curcumin and resveratrol. Incorporation of mucoadhesive agents such as chitosan further enhances nasal retention and drug uptake. Despite encouraging preclinical results, challenges remain in translating this approach clinically. Conclusion Intranasal NE-based drug delivery presents a transformative strategy for treating MDD and other CNS disorders. By integrating nanoscale formulation approaches with tailored pharmacokinetics, this system offers improved drug efficacy, safety, and patient adherence. Future research should focus on optimizing formulations, ensuring long-term stability, and advancing clinical translation for broader CNS applications.</p>","PeriodicalId":521353,"journal":{"name":"Drug metabolism and bioanalysis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148364713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Quantitative Efflux Ratio-Integrated Model for Passive Permeability Estimation from Caco-2 Assays.","authors":"Grace Zang, Chunyan Han, Xin Wang, Kent Wong, Zhongyuan Zhao, Tao Zhang","doi":"10.2174/0131173853500625260530130306","DOIUrl":"https://doi.org/10.2174/0131173853500625260530130306","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Reliable estimation of passive permeability in the presence of active efflux remains a key challenge in early drug discovery. In bidirectional Caco-2 assays, apparent permeability reflects both passive diffusion and transporter-mediated efflux, preventing direct determination of intrinsic passive permeability from baseline measurements. Existing approaches typically require additional experimental systems, increasing complexity and cost. This study aimed to develop a quantitative method to estimate passive permeability directly from standard Caco-2 data without additional assays.</p><p><strong>Methods: </strong>An empirical Efflux Ratio Integrated Model (ERIM) was developed, incorporating Efflux Ratio (ER) into a correction framework applied to bidirectional apparent permeability data. The model was evaluated using a dataset of 125 in-house compounds and 13 reference compounds. Performance was assessed through repeated train-test validation, comparison with a Global Average Model (GAM), and classification-based error analysis.</p><p><strong>Results: </strong>GAM showed systematic overestimation of passive permeability that increased with ER, resulting in a high false-positive rate. ERIM eliminated efflux-dependent bias, substantially reduced false-positive classifications, and maintained low false-negative rates, with consistent performance across validation rounds.</p><p><strong>Discussion: </strong>The conventional averaging method (GAM) showed that efflux-driven distortion on passive permeability estimate is systematic and can be corrected using ER and a scaling factor. Results showed reduced bias without increasing false negatives, supporting its utility for early-stage screening.</p><p><strong>Conclusion: </strong>ERIM provides a simple and practical framework for estimating passive permeability directly from a single Caco-2 assay by correcting efflux-related bias. This approach improves the interpretability of permeability data and supports more efficient compound prioritization in early-stage drug discovery.</p>","PeriodicalId":521353,"journal":{"name":"Drug metabolism and bioanalysis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148207638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formulation, Development, and In vitro Evaluation of Sustained Release Buccal Films for Optimized Memantine Therapy.","authors":"Dushyant, Subhashish Nayak, Vrint Panchal, Smita Narwal, Jagdeep Singh, Ashwani K Dhingra, Sakshi, Jasmeen Kaur, Neha Yadav, Jasvinder Saini","doi":"10.2174/0131173853466482260428064458","DOIUrl":"https://doi.org/10.2174/0131173853466482260428064458","url":null,"abstract":"<p><strong>Introduction: </strong>Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is employed in moderate to severe Alzheimer's disease but has the disadvantage of low oral bioavailability owing to first-pass metabolism and multiple doses. Buccal drug delivery is one such alternative that has received attention for enhancing systemic availability and patient compliance.</p><p><strong>Methods: </strong>Sustained-release buccal films of memantine hydrochloride were prepared by the solvent casting technique using Hydroxypropyl Methylcellulose (HPMC) and Carbopol 940 as film-forming and mucoadhesive polymers, polyethylene glycol 400 as plasticizer, and menthol as permeation enhancer. UV and FTIR were used for preformulation studies and for compatibility testing. The films were assessed for their physicochemical properties, tensile strength, swelling studies, surface pH, drug content, residence time, and in vitro release. Optimization of the result was carried out by statistical regression analysis with Design Expert® software.</p><p><strong>Results: </strong>The prepared films possessed uniform thickness, good mechanical properties, surface pH compatible with the buccal mucosa, and provided constant drug release for 8 h. FTIR studies revealed that there was no chemical incompatibility between memantine and excipients. F11 was found to have the highest drug content (90.1%), a good swelling index (19.4%), good folding endurance, and a conducive residence time of approximately 5 h.</p><p><strong>Discussion: </strong>The sustained release and the positive mucoadhesive properties observed are in line with those reported for other buccal film systems. The swelling profile and drug release kinetics were markedly affected by the polymer concentration.</p><p><strong>Conclusion: </strong>The developed sustained-release buccal films of memantine hydrochloride demonstrated favorable physicochemical and in vitro release characteristics, indicating their potential as a noninvasive alternative drug delivery system. Although buccal administration is theoretically capable of bypassing hepatic first-pass metabolism and improving systemic availability, such benefits could not be conclusively established in the absence of in vivo pharmacokinetic and ex vivo permeation studies. Therefore, further investigations are required to validate these potential advantages.</p>","PeriodicalId":521353,"journal":{"name":"Drug metabolism and bioanalysis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148207640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Routes of Drug Administration in Chronic Obstructive Pulmonary Disease: Evidence-based Evaluation.","authors":"Montasir Mohamedsaeed Ahmed Yousif, Rizwana Singanamala, Poornima Manjulatha Gari, Bhargav Eranti","doi":"10.2174/0131173853464075260427185435","DOIUrl":"https://doi.org/10.2174/0131173853464075260427185435","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) remains a major global healthcare burden, necessitating multimodal pharmacologic strategies optimized for effective drug delivery. Inhalation is the preferred route due to targeted pulmonary deposition, rapid onset, reduced systemic exposure, and lower dose requirements. Pressurized metered-dose inhalers, dry-powder inhalers, soft-mist inhalers, and nebulizers demonstrate proven efficacy; however, effectiveness is limited by patient technique, inspiratory capacity, and device-dependent variability. Oral agents, including corticosteroids, phosphodiesterase-4 inhibitors, and theophylline, provide systemic anti-inflammatory and bronchodilator effects but are constrained by adverse event profiles and narrow therapeutic windows. Parenteral therapy, such as intravenous corticosteroids and bronchodilators, remains primarily reserved for severe exacerbations; however, evidence suggests limited superiority over oral corticosteroids. Intravenous alpha-1 antitrypsin replacement offers a disease-modifying benefit in genetically deficient populations, slowing emphysema progression and improving survival. Transdermal nicotine replacement therapy contributes indirectly to COPD management via smoking cessation support. Collectively, inhalation continues to dominate COPD maintenance therapy, while systemic routes are reserved for specific indications. The optimal outcomes depend on individualized route selection based on disease severity, patient ability, and therapeutic goals.</p>","PeriodicalId":521353,"journal":{"name":"Drug metabolism and bioanalysis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148207633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}