Bastiancich C, Molinar C, Tchoghandjian A
… +2 more, Cavalli R, Scomparin A
Expert Opin Drug Deliv
· 2025 Dec · PMID 41042278
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INTRODUCTION: Dextrins are biodegradable, highly soluble, natural derivatives of starch, which occur in two main forms, either as linear polymers or as cyclic oligosaccharides, commonly known as cyclodextrins. The two st...INTRODUCTION: Dextrins are biodegradable, highly soluble, natural derivatives of starch, which occur in two main forms, either as linear polymers or as cyclic oligosaccharides, commonly known as cyclodextrins. The two structures present favorable features to be exploited in the development of drug delivery systems. AREAS COVERED: This review explores dextrin- and cyclodextrin-based polymeric systems as innovative platforms for drug delivery in the treatment of glioblastoma, one of the most aggressive and lethal brain tumors. Despite advances in oncology, glioblastoma remains largely incurable due to the absence of effective therapeutic protocols. Consequently, novel strategies are being investigated, including both local and systemic administration of chemotherapeutic and targeted agents. Cyclodextrins, in particular, show promise as drug carriers owing to their ability to interact with the blood - brain barrier and enhance drug permeation. We summarize key preclinical studies employing cyclodextrin-based systems to deliver diverse anticancer agents, including cytotoxic drugs, immunotherapies, oligonucleotides, and antioxidants. Special emphasis is placed on unmet clinical needs, the challenges of experimental models, and the advantages offered by cyclodextrin formulations in glioblastoma therapy. EXPERT OPINION: Albeit far from clinical application, cyclodextrin-based polymers hold a strong potential as innovative treatment against glioblastoma.
Iyer J, Hariharan A, Kanai R
… +4 more, Peng Y, Badwelan M, Sumita Y, Tran SD
Expert Opin Drug Deliv
· 2025 Dec · PMID 41042197
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INTRODUCTION: Systemic equilibrium, oral health, and digestion depend on the health of the salivary glands (SGs). SG disorders, such as Sjögren's syndrome, oral and maxillofacial cancer, and radiation-induced damage, are...INTRODUCTION: Systemic equilibrium, oral health, and digestion depend on the health of the salivary glands (SGs). SG disorders, such as Sjögren's syndrome, oral and maxillofacial cancer, and radiation-induced damage, are usually associated with xerostomia, which severely impacts the patient's quality of life. Current therapeutic modalities primarily provide symptomatic therapy without addressing the basic underlying tissue damage or promoting regeneration. Emerging pharmacological and stem cell treatments may restore SG function, but tailored delivery, effectiveness, and safety issues restrict their clinical application. AREAS COVERED: This review summarizes preclinical and clinical findings on systemic and localized stem cell and pharmaceutical drug administration. We discuss various SG conditions to match therapy methods to disease-specific demands and underline the necessity for accurate, efficient delivery systems to improve results and reduce adverse effects. We conclude with existing limits, future views, and prospective SG medicine regenerative therapy advancements. EXPERT OPINION: Advancements in drug and stem cell delivery systems for SGs offer the potential to move beyond symptomatic relief and instead regenerate damaged tissues. These approaches promise more targeted, cost-effective, and long-lasting therapies, though challenges like immune rejection, safety, and cost remain significant. Future research should focus on improving stem cell sources, delivery, and tracking, while integrating technologies such as gene editing, nanocarriers, and tissue engineering to enhance efficacy. Ultimately, treatment strategies are shifting toward regenerative solutions aimed at restoring SG function with fewer systemic side effects.
Pathak S, Bera R, Sharma A
… +5 more, Kakkar D, Kurmi BD, Srivasatava P, Ghosh M, Sharma N
Expert Opin Drug Deliv
· 2025 Dec · PMID 41042160
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INTRODUCTION: Colorectal cancer remains one of the most prevalent and lethal malignancies worldwide, with treatment often hampered by poor drug bioavailability, systemic toxicity, and resistance to conventional therapies...INTRODUCTION: Colorectal cancer remains one of the most prevalent and lethal malignancies worldwide, with treatment often hampered by poor drug bioavailability, systemic toxicity, and resistance to conventional therapies. Biomimetic nanocarriers have emerged as a promising strategy to overcome these limitations by combining nanotechnology with the biological functions of cell-derived membranes. AREAS COVERED: This review critically examines the design, fabrication, and application of biomimetic nanocarriers specifically for colorectal cancer. Focusing on various membrane coatings, including red blood cells, platelets, and cancer cells, and their role in enhancing drug delivery efficacy. It further explores the application of these nanocarriers in chemotherapy, immunotherapy, gene therapy, photothermal therapy, and cancer theranostics, while also discussing advances in targeting the unique tumor microenvironment of colorectal cancer.Literature was retrieved from PubMed, Scopus, Web of Science and Google Scholar databases covering publications from 2012 to May 2025. EXPERT OPINION: Despite encouraging preclinical results, the clinical translation of biomimetic nanocarriers faces challenges including scalability, membrane heterogeneity, immunogenicity, and regulatory hurdles. Furthermore, existing studies often overlook the unique features of the colorectal cancer tumor microenvironment. Future research should focus on precision nanomedicine tailored to colorectal cancer, addressing current limitations to enable safer, more effective, and targeted cancer management.
Khan TU, Sharaf M, Khan S
… +2 more, Ahmad K, Liu CG
Expert Opin Drug Deliv
· 2026 Jan · PMID 41041824
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INTRODUCTION: infections demand innovative therapeutic strategies due to rising antibiotic resistance. This review consolidates recent advances in nanoparticle (NP)-based drug delivery systems engineered to optimize ant...INTRODUCTION: infections demand innovative therapeutic strategies due to rising antibiotic resistance. This review consolidates recent advances in nanoparticle (NP)-based drug delivery systems engineered to optimize antimicrobial efficacy against . AREAS COVERED: We critically examine the design, functionality, and performance of metallic, polymeric, lipid-based, and biomimetic nano-carriers, highlighting their advantages over conventional antibiotic delivery. EXPERT OPINION: Key innovations include: Lipid-based systems enabling synergistic co-delivery of hesperidin (0.064 μg mL⁻¹) and clarithromycin (0.15 mg mL⁻¹) for enhanced drug bioavailability; Polymeric NPs (e.g. rhamnolipid-chitosan hybrids) achieving deep biofilm penetration ( > 99% eradication) within gastric mucus at minimal inhibitory concentrations (32-132 µg/mL). These nanoplatforms demonstrate precision gastric-mucosa targeting, improved penetration of biological barriers, and controlled antimicrobial release. By maximizing localized drug delivery while minimizing systemic exposure, NP-based systems address critical limitations of current therapies, including resistance and microbiota disruption. We further emphasize the need for clinical validation to translate these delivery technologies into standardized treatments, ultimately reducing the global burden of -associated diseases.
Awad N, Cruz DRD, Melaragno L
… +3 more, Pinhas S, Larson PJ, Dion GR
Expert Opin Drug Deliv
· 2025 Dec · PMID 41037004
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INTRODUCTION: Vocal fold (VF) scarring poses a significant challenge. It is characterized by prolonged and often irreversible impairment of vocal function due to loss of pliability and disruption of the lamina propria's...INTRODUCTION: Vocal fold (VF) scarring poses a significant challenge. It is characterized by prolonged and often irreversible impairment of vocal function due to loss of pliability and disruption of the lamina propria's native extracellular matrix. Current treatments remain largely palliative, aiming to improve glottic closure rather than restore normal tissue biomechanics. As research deepens into the wound healing pathways and fibrotic mechanisms underlying scar formation, injectable therapies are emerging as approaches to modulate healing and restore vibratory function. AREAS COVERED: This review outlines the pathophysiology of VF scarring and evaluates emerging injectable strategies designed to restore tissue architecture and function. These include biomaterial-based implants, antifibrotic and pro-regenerative biologics, stem cell therapies, and advanced drug delivery systems. The translational challenges include anatomical constraints, delivery precision, animal models, immune compatibility, degradation kinetics, and the lack of standardized outcome measures. EXPERT OPINION: The review highlights the ongoing research on injections of implants for VF scarring that support biomechanical properties and modulate local tissue repair. However, further advanced and long-term studies, including clinical trials, are needed to fully elucidate their safety, efficacy, and toxicity profiles. In addition, their scalability and reproducibility within pharmaceutical manufacturing must be rigorously validated to support clinical translation.
Expert Opin Drug Deliv
· 2026 Jan · PMID 41036766
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INTRODUCTION: Amygdalin, is arguably, one of the most controversial molecules found in nature, with several therapeutic properties, including anticancer, but there are concerns over its toxicity in healthy tissue alike,...INTRODUCTION: Amygdalin, is arguably, one of the most controversial molecules found in nature, with several therapeutic properties, including anticancer, but there are concerns over its toxicity in healthy tissue alike, which warrants a modified approach toward its utilization in therapy. AREAS COVERED: This review examines a rational approach toward its effective deployment in managing several diseases, anticancer, and anti-fibrotic, anti-inflammatory effects. The search for relevant articles was conducted by scouting the PubMed and Scopus on published articles from 2014-2025. We capture the key modulatory pathways of amygdalin that conveys several of its therapeutic effects and paradoxically, the observed toxicity in healthy tissue. The review contends that amygdalin remains as a formidable therapeutic contender for treating several diseases, if the dose can be attenuated through controlled release from nanotechnological-based formulation. EXPERT OPINION: Toxicity concerns and stability associated with amygdalin are best addressed through slow and controlled release from nano-encapsulation delivery systems. A further frontier can involve co or trio- nano-encapsulation of amygdalin with other therapeutic agents, whereby toxicity concerns and drug resistance are simultaneously addressed.
D'Souza AA, DiFrancesco V, Yang A
… +2 more, Bleier BS, Amiji MM
Expert Opin Drug Deliv
· 2026 Jan · PMID 41017598
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INTRODUCTION: Nose-to-brain drug delivery provides a promising noninvasive route to bypass the blood-brain barrier through direct nasal cavity-brain connections. Therapeutic agents reach the central nervous system via sy...INTRODUCTION: Nose-to-brain drug delivery provides a promising noninvasive route to bypass the blood-brain barrier through direct nasal cavity-brain connections. Therapeutic agents reach the central nervous system via systemic circulation or olfactory/trigeminal nerve pathways. Only the olfactory epithelium enables direct brain transport through olfactory neurons, bypassing the blood-brain barrier, while the respiratory epithelium primarily supports systemic absorption before CNS access via trigeminal nerves. AREAS COVERED: This review examines anatomical and functional differences between olfactory and respiratory epithelia, focusing on receptor, lectin, microbial, and enzymatic expression variations, particularly species-specific differences. These distinctions create opportunities for selective olfactory epithelium targeting. Key studies using formulation strategies and physical delivery methods to enhance olfactory-specific drug delivery are discussed, alongside analytical techniques for assessing olfactory accumulation. A systematic literature search across major databases through June 2025 supports these findings. EXPERT OPINION: Despite decades of research, nose-to-brain drug delivery faces unresolved challenges. Major limitations include imprecise targeting of the olfactory epithelium and the lack of standardized in vitro and in vivo models for determining exact transport mechanisms and enabling cross-comparisons. Addressing these gaps is essential for advancing targeted nose-to-brain drug delivery systems.
Seifelnasr A, Si X, Zhang JY
… +3 more, Luo MZ, Lei RL, Xi J
Expert Opin Drug Deliv
· 2025 Dec · PMID 41017593
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INTRODUCTION: Nasal sprays offer a versatile, noninvasive delivery route for topical, systemic, immunological, and nose-to-brain therapies, yet effective targeting is limited by nasal anatomical complexity and physiologi...INTRODUCTION: Nasal sprays offer a versatile, noninvasive delivery route for topical, systemic, immunological, and nose-to-brain therapies, yet effective targeting is limited by nasal anatomical complexity and physiological constraints. AREAS COVERED: The literature related suboptimal intranasal spray deposition to nasal valve constriction, convoluted nasal passages, mucociliary clearance, and vast geometrical variability. This review examined recent strategies that enhanced dosimetry realism and improved target delivery: (1) including mucus coating and nasal cycle effects, (2) optimizing delivery protocols such as the spray angle, head position, and dosing regimen, (3) engineering device features to improve targeting, and (4) tailoring formulation properties like the viscosity and surface tension to support liquid film translocation. Experimental findings highlighting protocol-driven improvements in spray targeting to the nasopharynx and olfactory region are also discussed. EXPERT OPINION: The effectiveness of nasal sprays hinges on their ability to deliver medication beyond the anterior nasal cavity to the intended target sites. Achieving this requires not only optimized spray dynamics and device design, but also the strategic use of liquid film translocation following initial deposition. Advances in physiologically realistic models and anatomically guided protocols will be key to unlocking the full therapeutic potential of nasal spray technologies.
Expert Opin Drug Deliv
· 2025 Dec · PMID 40991896
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BACKGROUND: In the present study, we fabricated a multifunctional hydrogel nanocomposite for wound healing applications. RESEARCH DESIGN AND METHODS: Computational simulations were employed to optimize gelatin and synthe...BACKGROUND: In the present study, we fabricated a multifunctional hydrogel nanocomposite for wound healing applications. RESEARCH DESIGN AND METHODS: Computational simulations were employed to optimize gelatin and synthesize Ti3AlC2 (104) and clarify gelatin adsorption behavior on Ti3AlC2 (104). The experiments concentrated on the synthesis, characterization, and integration of Mxene into a gelatin hydrogel. The MTT assay, hemolysis assay, and antibacterial assay were performed to assess the biological activities of the hydrogels, and a full-thickness wound was induced on a rat for the animal experiments. RESULTS: The chosen composite exhibited a satisfactory docking score, with a binding energy of - 115.408 kcal mol. The results showed that the synthesized MXenes had a zeta potential of +24.5 ± 3.2 mV and a hydrodynamic size of 2.091 ± 0.32 μm. The hydrogel that was made had a porous structure, was biodegradable, and could soak up much water. The biological test showed the hydrogel was biocompatible, hemocompatible, and antibacterial. The animal trials demonstrated that the MXene-loaded gelatin hydrogel expedited wound healing. CONCLUSIONS: The fabricated gelatin hydrogel loaded with MXenes nanocomposite can be applied to contaminated wounds to eradicate the contamination and accelerate the healing process.
Lozza I, Fraguas-Sánchez AI, Martín-Sabroso C
… +1 more, Torres-Suárez AI
Expert Opin Drug Deliv
· 2025 Dec · PMID 40985997
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INTRODUCTION: In situ forming implants (ISFIs) are long-acting drug delivery systems that solidify at the injection site, creating a depot for sustained drug release from days to months. Compared with preformed implants,...INTRODUCTION: In situ forming implants (ISFIs) are long-acting drug delivery systems that solidify at the injection site, creating a depot for sustained drug release from days to months. Compared with preformed implants, ISFIs offer unique advantages, including easier and more convenient administration and simpler manufacturing. Among the different types, solvent-based ISFIs are the most extensively studied and developed formulations. AREAS COVERED: This review analyses advances in solvent-based ISFIs at both preclinical and clinical levels, with emphasis on formulation strategies and therapeutic applications. A literature search was conducted using PubMed and WOS. EMA and FDA databases were also consulted. EXPERT OPINION: Solvent-based ISFIs represent an important strategy for achieving long-lasting effects with a single administration independent of patient compliance. Their main impact has been in mental and substance use disorders, but they are also useful for local effects. To date, one formulation has been approved for periodontitis, though applications in ocular diseases and osteoarthritis are anticipated. A key formulation challenge is to reduce the initial drug release. Most marketed formulations are based on PLGA/PLA dissolved in NMP. Recently, DMSO and PEGylated-based-ISFIs have been approved, which generally provide better drug release control and will likely lead to the development of new formulations.
Aamir Hassan M, Abdelaziz M, Noor S
… +4 more, Nangmo Kemda P, Tan A, Park J, Rotello VM
Expert Opin Drug Deliv
· 2025 Dec · PMID 40981743
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INTRODUCTION: Antimicrobial resistance (AMR) in bacterial infections is a critical global health threat, contributing significantly to increased morbidity and mortality. This challenge is further amplified by biofilms th...INTRODUCTION: Antimicrobial resistance (AMR) in bacterial infections is a critical global health threat, contributing significantly to increased morbidity and mortality. This challenge is further amplified by biofilms that act as a protective barrier around bacteria, limiting the effective action of antibiotics and host immune responses. AREAS COVERED: This review highlights the potential of nanoemulsion (NE) systems in delivering hydrophobic payloads, particularly essential oils (EOs), into biofilms, negatively charged extracellular polymeric substance (EPS) matrix. While essential oils exhibit strong antimicrobial properties, their effectiveness against biofilms is restricted due to poor bioavailability and limited biofilm penetration. EXPERT OPINION: NE systems employing natural, semisynthetic, and synthetic polymeric scaffolds offer an effective delivery method for EOs, enabling enhanced penetration into the negatively charged EPS matrix of biofilms. These therapeutics have significant potential for treating refractory biofilm-related AMR infections.
Pan S, Dong N, Yuan H
… +6 more, Zhang Y, He H, Yin T, Wang Y, Gou J, Tang X
Expert Opin Drug Deliv
· 2025 Dec · PMID 40977331
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BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists have demonstrated significant clinical efficacy in recent years for the treatment of type 2 diabetes mellitus (T2DM) and obesity. However, their widespread ap...BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists have demonstrated significant clinical efficacy in recent years for the treatment of type 2 diabetes mellitus (T2DM) and obesity. However, their widespread application remains constrained by limitations such as low oral bioavailability and poor patient compliance due to frequent injections. This study developed a biphasic delivery system (Ex-NPs-gel) integrating poly(lactic-co-glycolic acid)-poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PLGA-PEG-PLGA) thermosensitive hydrogel with nanoparticles (NPs) for sustained-release injectable formulations. METHODS: Exenatide-loaded nanoparticles (Ex-NPs) were prepared via the double emulsion solvent evaporation method and encapsulated into PLGA-PEG-PLGA hydrogel. The prepared NPs and hydrogel composite were subsequently evaluated for their physicochemical properties and in vitro/in vivo performance. RESULTS: In vitro studies demonstrated that Ex-NPs-gel achieved sustained exenatide release over 31 days with an initial burst release below 9% within the first 24 h. In T2DM rat models, a single administration induced fasting blood glucose stabilization for over 15 days and restored hepatic/pancreatic functions. CONCLUSIONS: This system overcomes technical bottlenecks of conventional PLGA carriers and single-phase gels through modulation of release kinetics, offering a biocompatible and clinically translatable solution for long-acting polypeptide delivery.
Expert Opin Drug Deliv
· 2025 Dec · PMID 40974615
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INTRODUCTION: Recent advances in nanoformulations are reshaping the treatment landscape for helminthiasis by addressing critical challenges such as drug resistance, poor bioavailability, and off-target effects. AREAS COV...INTRODUCTION: Recent advances in nanoformulations are reshaping the treatment landscape for helminthiasis by addressing critical challenges such as drug resistance, poor bioavailability, and off-target effects. AREAS COVERED: This review examines current innovations in nanotechnology applied to anthelmintic therapy, with a particular focus on lipid- and polymer-based systems designed to enhance drug solubility, stability, and targeted delivery. A comprehensive literature search was performed to identify recent developments, highlight preclinical and translational studies, and evaluate the performance of solid lipid nanoparticles, nanoemulsions, and self-nanoemulsifying drug delivery systems. Relevant articles were retrieved from peer-reviewed journals indexed in PubMed, Scopus, and Web of Science, covering publications up to June 2025. EXPERT OPINION: The integration of nanotechnologies into helminthiasis treatment offers promising therapeutic advantages but faces important challenges related to industrial scalability, regulatory approval, and implementation in low-resource settings. Addressing these issues requires coordinated efforts between academia, industry, and public health stakeholders. The review outlines key considerations for technology transfer and commercialization, underscoring the importance of cost-effectiveness, patient acceptability, and cross-sector collaboration to ensure the successful translation of nanomedicine-based solutions for neglected tropical diseases.
Jog S, Dighe S, Nathani K
… +4 more, Waghmare A, Mangrulkar SV, Sawarkar SP, Omri A
Expert Opin Drug Deliv
· 2025 Dec · PMID 40964960
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BACKGROUND: Felodipine (FLD) is an L-type calcium channel blocker with pronounced neuroprotection against Alzheimer's disease (AD). Unfortunately, the efficacy of FLD has been impeded by limited solubility, poor bioavail...BACKGROUND: Felodipine (FLD) is an L-type calcium channel blocker with pronounced neuroprotection against Alzheimer's disease (AD). Unfortunately, the efficacy of FLD has been impeded by limited solubility, poor bioavailability, and sub-optimal accumulation. Thus, the current study unfolds the potential of nanostructured lipid carriers based on in-situ gel of FLD (FLD-NLCs gel) to ameliorate dementia. METHODS: The FLD-contained NLCs were prepared using the microemulsion-sonication method and further integrated into thermosensitive gel comprised poloxamer 407 and HPMC K4M. The formulation was evaluated by ex-vivo permeation study, cell culture studies, and in-vivo efficacy study. The toxicity of formulation was assessed by HET-CAM assay, and nasal cilitoxicity study. RESULTS: The optimized FLD-NLCs had nanoscaled dimension, spherical shape, and augmented %EE (~96%). The FLD-NLCs gel displayed biphasic release, with ~1.3-fold higher permeation as relative to free FLD. The HET-CAM assay and cell culture study revealed compatible nature of formulation. The in-vivo biochemical, neurotransmitter, and inflammatory marker determination revealed neuroprotective and restorative potential of the FLD-NLCs gel. CONCLUSIONS: The repurposing tactic of FLD presents a viable concept to combat AD. Also, the NLC-based temperature responsive intranasal gel exemplifies a practical approach to augment the efficacy of FLD.
Hummel MA, Shaw A, Liu MS
… +3 more, Jaiswal A, Smith JP, Bertoch T
Expert Opin Drug Deliv
· 2025 Dec · PMID 40957583
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BACKGROUND: MR-107A-02 is a novel faster dissolving oral formulation of meloxicam to provide rapid absorption and faster onset of action in acute pain settings. This study compared the single-dose pharmacokinetics of MR-...BACKGROUND: MR-107A-02 is a novel faster dissolving oral formulation of meloxicam to provide rapid absorption and faster onset of action in acute pain settings. This study compared the single-dose pharmacokinetics of MR-107A-02 tablets to reference meloxicam (Mobic®) tablets under fasting conditions. RESEARCH DESIGN AND METHODS: A single-dose, randomized, two-period crossover study was conducted at a single center in India. Healthy adult volunteers, aged 18-45 years, were randomized to receive a single, oral dose of 15 mg (1 × 15 mg) of MR-107A-02 or reference. Plasma samples were analyzed for meloxicam using LC-MS/MS. Pharmacokinetic parameters were derived using non-compartmental analysis, and 90% geometric confidence intervals for test/reference ratios were calculated. Safety was assessed through adverse event (AE) monitoring. RESULTS: Eighteen adult male volunteers were randomized and 16 completed the study. MR-107A-02 showed faster absorption, with a geometric mean C value of 2734.342 (ng/mL) compared to reference 1592.102 (ng/mL) and a significantly shorter median T (hour) (0.75 vs 4.00). There were no AEs, or serious AEs reported. CONCLUSIONS: MR-107A-02 demonstrated more rapid absorption than reference, as evidenced by a higher C, and shorter T values. These findings highlight the potential utility of oral MR-107A-02's fast-release design in an acute pain setting.