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Due to the complex nature of Alzheimer’s disease (AD), it begins insidiously in the brain many years before the appearance of the first symptoms and is usually diagnosed, when the disease is progressive and symptoms have appeared. It can be said that AD’s emergence is almost untrackable and the straightforward mechanism of AD is still unclear for the most part. Therefore, any kind of research on the emergence of AD can lead to valuable results for predicting and treating AD. Previously, we proposed a novel mathematical model based on cellular automata for the study of Alzheimer’s disease progress. In this paper, cellular automata (CA) mathematical modeling is used as a tool for simulation and experimenting with drugs’ effects in this far-fetched situation. For this goal, immune system interactions and neuron-to-neuron communications are assumed to have prominent roles. We have used the CA network, pathophysiological process, and physiological realities to get a clear insight into neuron-to-neuron communications. Our simple model investigates the influence of three Acetylcholinesterase Inhibitor injections, including Donepezil, Rivastigmine, and Galantamine on the reduction of defined factors such as Alzheimer’s Rate (AR), Critical Rate (CR), and Warning Rate (WR). It is shown that using drugs has different effects on the betterment of neurons and can decrease AR and CR factors and enhance WR, many years before the appearance of symptoms. [ABSTRACT FROM AUTHOR]

In this study, spectrophotometric determination of donepezil and rivastigmine in healthy human urine samples was carried out by the statistical method. Partial least squares (PLS) and principal component regression (PCR) from multivariate calibration methods were used to evaluate the data obtained from the UV–Vis spectroscopy analysis of the urine sample. Mixtures of each early substance were prepared prior to urine sample analysis, and simultaneous determination of donepezil and rivastigmine was performed on the established chemometric model without any prior separation. The calibration curves of each drug were analyzed, and linearity values were also analyzed. For donepezil and rivastigmine, they were 0.9989 and 0.9997, respectively, and were linear over the concentration range of the synthetic mixture. When both chemometric methods (PLS and PCR) were evaluated in terms of accuracy and reproducibility, very high recoveries and small standard deviations were determined. In the PLS method, the standard error of prediction (SEC), the sum of the prediction residual errors (PRESS), the limit of quantitation (LOQ), and the limit of detection (LOD) values were 0.015, 0.0030, 0.067, 0.24, 0.018, 0.0042, 0.089, and 0.301 for donepezil and rivastigmine, respectively. In the PCR method, SEC, PRESS, LOD, and LOQ values are 0.016, 0.0054, 0.066, and 0.23 for donepezil and 0.022, 0.0062, 0.091, and 0.300 for rivastigmine. Chemometrics is used for speed, simplicity, and reliability. The proposed methods have been successfully applied to a sample of urine. [ABSTRACT FROM AUTHOR]

Objective: Alzheimer's disease (AD), affecting over 55 million people globally, poses a substantial public health challenge. Early diagnosis and appropriate treatment are vital to slowing its progression and enhancing patient quality of life. The fixed-dose combination of citicoline with rivastigmine emerges as a promising strategy AD treatment. Methods: A real-time Delphi consensus was reached with the participation of 11 Mexican experts. Results: The combination offers neuroprotective benefits, enhancing neuronal regeneration and reducing glutamate levels linked to neuronal damage in AD. These effects translate into improved cognitive function and delayed cognitive decline in AD. Conclusions: The Mexican Consensus for the Combined Management of AD endorses this fixed-dose combination of rivastigmine with citicoline as a new therapeutic perspective. Its efficacy and safety make it a valuable option for the treatment of this neurodegenerative disease. [ABSTRACT FROM AUTHOR]

In this study, we report the synthesis of 3-((2-(4-chloro-5-ethoxy-2-nitrophenoxy)acetamido)methyl)phenyl-dimethylcarbamate, designed on the basis of the structures of the commercial acetylcholinesterase inhibitor drug rivastigmine and a substituted aryloxyacetic acid, aiming at a multi-target approach to the therapy of Alzheimer's disease. The hybrid was obtained thanks to a synthesized intermediate by-product. The compound was fully characterized by using 1H and 13C NMR, FT-IR and HRMS. [ABSTRACT FROM AUTHOR]

This research aimed to create and optimize a transethosomal patch containing Rivastigmine Hydrogen Tartarate, a cholinesterase inhibitor, for the symptomatic management of Alzheimer's disease that would reduce drug loading and patch size. Transethosomes are elastic vesicles made up of phospholipids, ethanol, and edge activator. Transethosomes of Rivastigmine were prepared by cold method, which were then incorporated into a transdermal adhesive patch prepared by solvent casting method. The transethosomes were optimised using the central composite design. The optimized transethosomes showed low vesicle size, good entrapment efficiency and enhanced transdermal flux. The electron microscopy revealed that the vesicles were uniform and sphere-shaped, also the vesicle surface was found to be smooth. Rivastigmine Hydrogen Tartarate was released slowly in the study, and the mechanism of drug release followed the Korsemeyer-Peppas model. Transethosomal formulation showed significant increase in the steady state flux to 2.18 times than the pure drug solution. Also, the transethosomal patch showed significant increase in the steady state flux to 1.55 times than the conventional patch. Based on the results, Rivastigmine Hydrogen Tartarate loaded transethosomal patch was the best formulation since it provided long-term drug release. [ABSTRACT FROM AUTHOR]

The article describes the case of a 79-year old Caucasian man who was treated with donepezil after developing a pruritic erythematous maculopapular eruption at the application site of rivastigmine transdermal patches, which was used to treat his Lewy body disease. The patient's skin lesions did not regress after antihistaminic treatment with cetirizine. A Naranjo scale assessment showed the high probability of the relation of cutaneous adverse effects with rivastigmine transdermal patches.

Alzheimer’s disease is a neurodegenerative disorder with polygenic etiology. Genetic risk variants for Alzheimer’s disease differ among populations. Thus, discovering them in each population is clinically important. A total of 118 patients and 97 controls for VDR rs11568820 and 88 patients and 100 healthy controls for MTHFR C677T polymorphism were genotyped to evaluate the association of these polymorphisms with late-onset Alzheimer’s disease in the Iranian population, along with their impacts on the response to Rivastigmine treatment. The VDR C allele was significantly associated with Alzheimer’s disease and provided protection against it (P = 0.003, RR = 1.14, 95% CI 1.04–1.24), while the T allele increased susceptibility (P = 0.003, RR = 1.93, 95% CI 1.23–3.02). These results were also considerable upon excluding the effect of APOE ε4 allele. The Prevalence-corrected Positive Predictive Value was 1.71% for the VDR CC genotype and 4% for the VDR CT genotype, indicating lower and almost twofold higher chances of developing Alzheimer’s disease, respectively. No significant correlation was observed between MTHFR C677T and Alzheimer’s disease. Based on our pharmacogenetic study, MTHFR T allele carriers lacking APOE ε4 allele showed a better response to Rivastigmine treatment after a 2-year follow-up. Moreover, patients with VDR CC genotype displayed milder Alzheimer’s disease, particularly when coincided with the APOE ε4 allele. The VDR rs11568820 polymorphism affects both Alzheimer’s disease risk and the response to Rivastigmine in Iranian patients. Also, MTHFR C677T polymorphism may play a role in the response to Rivastigmine, through a pathway that needs to be elucidated in future studies. [ABSTRACT FROM AUTHOR]

A series of new 1,2,4-oxadiazole-based derivatives were synthesized and evaluated for their anti-AD potential. The results revealed that eleven compounds (1b, 2a-c, 3b, 4a-c, and 5a-c) exhibited excellent inhibitory potential against AChE, with IC50 values ranging from 0.00098 to 0.07920 µM. Their potency was 1.55 to 125.47 times higher than that of donepezil (IC50 = 0.12297 µM). In contrast, the newly synthesized oxadiazole derivatives with IC50 values in the range of 16.64–70.82 µM exhibited less selectivity towards BuChE when compared to rivastigmine (IC50 = 5.88 µM). Moreover, oxadiazole derivative 2c (IC50 = 463.85 µM) was more potent antioxidant than quercetin (IC50 = 491.23 µM). Compounds 3b (IC50 = 536.83 µM) and 3c (IC50 = 582.44 µM) exhibited comparable antioxidant activity to that of quercetin. Oxadiazole derivatives 3b (IC50 = 140.02 µM) and 4c (IC50 = 117.43 µM) showed prominent MAO-B inhibitory potential. They were more potent than biperiden (IC50 = 237.59 µM). Compounds 1a, 1b, 3a, 3c, and 4b exhibited remarkable MAO-A inhibitory potential, with IC50 values ranging from 47.25 to 129.7 µM. Their potency was 1.1 to 3.03 times higher than that of methylene blue (IC50 = 143.6 µM). Most of the synthesized oxadiazole derivatives provided significant protection against induced HRBCs lysis, revealing the nontoxic effect of the synthesized compounds, thus making them safe drug candidates. The results unveiled oxadiazole derivatives 2b, 2c, 3b, 4a, 4c, and 5a as multitarget anti-AD agents. The high AChE inhibitory potential can be computationally explained by the synthesized oxadiazole derivatives' significant interactions with the AChE active site. Compound 2b showed good physicochemical properties. All these data suggest that 2b could be considered as a promising candidate for future development. [ABSTRACT FROM AUTHOR]

Rivastigmine is one of the several pharmaceuticals widely prescribed for the treatment of Alzheimer's disease. However, its practical synthesis still faces many issues, such as the involvement of toxic metals and harsh reaction conditions. Herein, we report a chemo‐enzymatic synthesis of Rivastigmine. The key chiral intermediate was synthesized by an engineered alcohol dehydrogenase from Lactobacillus brevis (LbADH). A semi‐rational approach was employed to improve its catalytic activity and thermal stability. Several LbADH variants were obtained with a remarkable increase in activity and melting temperature. Exploration of the substrate scope of these variants demonstrated improved activities toward various ketones, especially acetophenone analogs. To further recycle and reuse the biocatalyst, one LbADH variant and glucose dehydrogenase were co‐immobilized on nanoparticles. By integrating enzymatic and chemical steps, Rivastigmine was successfully synthesized with an overall yield of 66 %. This study offers an efficient chemo‐enzymatic route for Rivastigmine and provides several efficient LbADH variants with a broad range of potential applications. [ABSTRACT FROM AUTHOR]

Memory is one of the most important abilities of our brain. The process of memory and learning is necessary for the proper existence of humans in the surrounding environment. However, sometimes there are unfavourable changes in the functioning of the brain and memory deficits occur, which may be associated with various diseases. Disturbances in the cholinergic system lead to abnormalities in memory functioning and are an essential part of clinical symptoms of many neurodegenerative diseases. However, their treatment is difficult and still unsatisfactory; thus, it is necessary to search for new drugs and their targets, being an alternative method of mono- or polypharmacotherapy. One of the possible strategies for the modulation of memory-related cognitive disorders is connected with the endocannabinoid system (ECS). The aim of the present study was to determine for the first time the effect of administration of natural cannabinoid compound (cannabidiol, CBD) and rivastigmine alone and in combination on the memory disorders connected with cholinergic dysfunctions in mice, provoked by using an antagonist of muscarinic cholinergic receptor—scopolamine. To assess and understand the memory-related effects in animals, we used the passive avoidance (PA) test, commonly used to examine the different stages of memory. An acute administration of CBD (1 mg/kg) or rivastigmine (0.5 mg/kg) significantly affected changes in scopolamine-induced disturbances in three different memory stages (acquisition, consolidation, and retrieval). Interestingly, co-administration of CBD (1 mg/kg) and rivastigmine (0.5 mg/kg) also attenuated memory impairment provoked by scopolamine (1 mg/kg) injection in the PA test in mice, but at a much greater extent than administered alone. The combination therapy of these two compounds, CBD and rivastigmine, appears to be more beneficial than substances administered alone in reducing scopolamine-induced cognitive impairment. This polytherapy seems to be favourable in the pharmacotherapy of various cognitive disorders, especially those in which cholinergic pathways are implicated. [ABSTRACT FROM AUTHOR]

We conducted a systematic review evaluating the efficacy of rivastigmine augmentation for treatmentrefractory posttraumatic stress disorder (PTSD). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. The databases Ovid MEDLINE, PubMed, CINAHL, and EMBASE were searched using key words: 'rivastigmine' OR 'Exelon' OR 'rivastigmine augmentation' OR 'Exelon augmentation' AND 'posttraumatic stress disorder*' OR 'post-traumatic stress disorder*' OR 'PTSD' OR 'combat disorder*' OR 'post-traumatic symptoms'. The asterisk specified plural forms of the relevant word. Four papers were identified, comprising one double-blind randomised controlled trial, one non-controlled open trial, one case series (presenting three case studies), and one paper with two case studies. The randomised controlled trial found no statistically significant difference in efficacy, using the PTSD CheckList'Military Version as the relevant outcomes measure, between the active add-on rivastigmine interventions and placebo or treatment as usual. The open trial, although reporting relatively positive outcomes, had a weak study design and lacked reporting of key information, including participant sex and age and pre-rivastigmine PTSD measures. The assessment of efficacy was based on participants' reporting of subjective benefits, and clinician-rating using a Clinical Global Impression, rather than established PTSD assessments scales. Although the five case studies reported improvement in PTSD symptoms, there were confounding factors and limitations in clinical and demographic data, warranting caution regarding attributed benefits. There is a lack of methodologically robust evidence supporting the efficacy of add-on rivastigmine for the treatment of refractory PTSD. Additional research may help in further evaluating its possible clinical efficacy. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is characterized by the accumulation of beta-amyloid plaques and neurofibrillary tangles. Effective therapeutic strategies involve inhibiting the formation of beta-amyloid aggregates and destabilizing existing ones. A significant challenge in current treatments is the inability of therapeutic agents to cross the blood-brain barrier, a limitation addressed by employing drug nanocarriers. This study investigates the interactions between memantine, rivastigmine, beta-amyloid structures, and graphene oxide nanocarriers using molecular docking and in silico methods. The goal is to enhance drug development through cost-effective and efficient computational techniques. Results indicate that the binding energies for memantine-beta-amyloid and rivastigmine-beta-amyloid complexes are −9.03 kcal/mol and −7.81 kcal/mol, respectively, suggesting superior stability for the memantine-beta-amyloid complex. The electrostatic energies are −1.91 kcal/mol for memantine and −0.81 kcal/mol for rivastigmine, further supporting the greater stability of the memantine complex. Additionally, memantine's interaction with graphene oxide results in more negative adsorption energy (−92.47 kJ/mol) compared to rivastigmine (−86.36 kJ/mol), indicating a stronger binding affinity. The charge transfer (Q) values are −0.41 kJ/mol for memantine and −0.33 kJ/mol for rivastigmine. The negative enthalpy (ΔH) of −85.71 kJ/mol and Gibbs free energy (ΔG) of −41.52 kJ/mol for the memantine-graphene oxide interaction suggest a spontaneous process. Both memantine and rivastigmine display similar electronic properties, but memantine shows a more effective interaction with graphene oxide, likely due to its amine functional group and spatial configuration. The adsorption energy analysis confirms that memantine forms a more stable complex with graphene oxide than rivastigmine.

INTRODUCTION: This guideline establishes clinical practice recommendations for the management of rapid eye movement sleep behavior disorder (RBD) in adults. METHODS: The American Academy of Sleep Medicine (AASM) commissioned a task force of experts in sleep medicine to develop recommendations and assign strengths based on a systematic review of the literature and an assessment of the evidence using Grading of Recommendations, Assessment, Development and Evaluation methodology. The task force provided a summary of the relevant literature and the certainty of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations that support the recommendations. The AASM Board of Directors approved the final recommendations. GOOD PRACTICE STATEMENT: The following good practice statement is based on expert consensus, and its implementation is necessary for the appropriate and effective management of patients with RBD: It is critically important to help patients maintain a safe sleeping environment to prevent potentially injurious nocturnal behaviors. In particular, the removal of bedside weapons, or objects that could inflict injury if thrown or wielded against a bed partner, is of paramount importance. Sharp furniture like nightstands should be moved away or their edges and headboard should be padded. To reduce the risk of injurious falls, a soft carpet, rug, or mat should be placed next to the bed. Patients with severe, uncontrolled RBD should be recommended to sleep separately from their partners, or at the minimum, to place a pillow between themselves and their partners. RECOMMENDATIONS: The following recommendations, with medications listed in alphabetical order, are a guide for clinicians in choosing a specific treatment for RBD in adults. Each recommendation statement is assigned a strength (strong or conditional). A strong recommendation (ie, We recommend…) is one that clinicians should follow under most circumstances. A conditional recommendation (ie, We suggest…) is one that requires that the clinician use clinical knowledge and experience and strongly consider the patients values and preferences to determine the best course of action. UNLABELLED: Adult patients with isolated RBD. UNLABELLED: 1. The AASM suggests that clinicians use clonazepam (vs no treatment) for the treatment of isolated RBD in adults. (CONDITIONAL). UNLABELLED: 2. * The AASM suggests that clinicians use immediate-release melatonin (vs no treatment) for the treatment of isolated RBD in adults. (CONDITIONAL). UNLABELLED: 3. * The AASM suggests that clinicians use pramipexole (vs no treatment) for the treatment of isolated RBD in adults. (CONDITIONAL). UNLABELLED: 4. The AASM suggests that clinicians use transdermal rivastigmine (vs no treatment) for the treatment of isolated RBD in adults with mild cognitive impairment. (CONDITIONAL). UNLABELLED: Adult patients with secondary RBD due to medical condition. UNLABELLED: 5. * The AASM suggests that clinicians use clonazepam (vs no treatment) for the treatment of secondary RBD due to medical condition in adults. (CONDITIONAL). UNLABELLED: 6. * The AASM suggests that clinicians use immediate-release melatonin (vs no treatment) for the treatment of secondary RBD due to medical condition in adults. (CONDITIONAL). UNLABELLED: 7. The AASM suggests that clinicians use transdermal rivastigmine (vs no treatment) for the treatment of secondary RBD due to medical condition (Parkinson disease) in adults. (CONDITIONAL). UNLABELLED: 8. * The AASM suggests that clinicians not use deep brain stimulation (DBS; vs no treatment) for the treatment of secondary RBD due to medical condition in adults. (CONDITIONAL). UNLABELLED: Adult patients with drug-induced RBD. UNLABELLED: 9. * The AASM suggests that clinicians use drug discontinuation (vs drug continuation) for the treatment of drug-induced RBD in adults. (CONDITIONAL). UNLABELLED: * The Recommendations section of this paper includes remarks that provide additional context to guide clinicians with implementation of this recommendation. CITATION: Howell M, Avidan AY, Foldvary-Schaefer N, et al. Management of REM sleep behavior disorder: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2023;19(4):759-768.

Background: Few reviews have addressed delirium prevention among intermediate to high‐risk older surgical patients. Aims: To map preoperative delirium prevention interventions for older surgical patients at intermediate to high risk of developing delirium, assess outcomes and identify gaps in knowledge. Design: Systematic narrative review of randomised controlled trials reported following the PRISMA checklist. Methods: A systematic search was conducted of the literature published from 1990 to October 2022 in Medline, CINAHL and Ageline and of the grey literature in Google Scholar. Randomised controlled trials were retrieved that assessed the effectiveness of preoperative delirium prevention interventions for older surgical patients at intermediate to high risk of delirium. Data were extracted using a data extraction tool, and results were tabulated. Studies were assessed for bias using the Cochrane Collaboration Risk of Bias tool. Results: Twenty‐one studies met the selection criteria including N = 5096 participants. Two studies tested cognitive training, two studies tested fascia iliaca compartment block and one study assessed femoral nerve block. Ten studies tested prophylactic medications including methylprednisolone. Five studies investigated geriatric assessment and management. One study assessed transcutaneous electrical acupoint stimulation. In the two studies testing fascia iliaca compartment block, there was a reduction in postoperative delirium for orthopaedic patients. Methylprednisolone reduced postoperative delirium in orthopaedic patients and in those undergoing gastrointestinal surgery. Results of all other interventions on the occurrence of postoperative delirium and additional outcomes including the severity and duration of delirium were inconclusive. Conclusions: Despite the promising results for fascia iliaca compartment block and methylprednisolone, there is limited knowledge regarding evidence‐based delirium prevention interventions. Most studies had small sample sizes indicating that the current evidence is exploratory. There is an urgent need for the funding and conduct of trials to test preventative interventions for older surgical patients at intermediate to high risk of developing delirium. [ABSTRACT FROM AUTHOR]

Background An updated time-trend analysis of anti-dementia drugs (ADDs) is lacking. The aim of this study is to assess the incident rate (IR) of ADD in individuals with dementia using real-world data. Setting Primary care data (country/database) from the UK/CPRD-GOLD (2007–20), Spain/SIDIAP (2010–20) and the Netherlands/IPCI (2008–20), standardised to a common data model. Methods Cohort study. Participants: dementia patients ≥40 years old with ≥1 year of previous data. Follow-up: until the end of the study period, transfer out of the catchment area, death or incident prescription of rivastigmine, galantamine, donepezil or memantine. Other variables: age/sex, type of dementia, comorbidities. Statistics: overall and yearly age/sex IR, with 95% confidence interval, per 100,000 person-years (IR per 105 PY (95%CI)). Results We identified a total of (incident anti-dementia users/dementia patients) 41,024/110,642 in UK/CPRD-GOLD, 51,667/134,927 in Spain/SIDIAP and 2,088/17,559 in the Netherlands/IPCI. In the UK, IR (per 105 PY (95%CI)) of ADD decreased from 2007 (30,829 (28,891–32,862)) to 2010 (17,793 (17,083–18,524)), then increased up to 2019 (31,601 (30,483 to 32,749)) and decrease in 2020 (24,067 (23,021–25,148)). In Spain, IR (per 105 PY (95%CI)) of ADD decreased by 72% from 2010 (51,003 (49,199–52,855)) to 2020 (14,571 (14,109–15,043)). In the Netherlands, IR (per 105 PY (95%CI)) of ADD decreased by 77% from 2009 (21,151 (14,967–29,031)) to 2020 (4763 (4176–5409)). Subjects aged ≥65–79 years and men (in the UK and the Netherlands) initiated more frequently an ADD. Conclusions Treatment of dementia remains highly heterogeneous. Further consensus in the pharmacological management of patients living with dementia is urgently needed. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disease that affects a wide range of populations and is the primary cause of death in various countries. The treatment of AD is still restricted to oral conventional medicines that act only superficially. Fabrication of intranasal solid lipid nanoparticulate system for the uptake of therapeutic agents will act as a convincing approach with limited off-site toxicity and increased pharmacological activity. The objective of this study was to formulate, optimize, and evaluate the efficiency of rivastigmine tartrate (RT)-loaded intranasal solid lipid nanoparticles (SLNs) employing the solvent-evaporation diffusion method. To optimize the formulation parameters, the central composite design (CCD) was used. Lipid concentration (X1) and surfactant concentration (X2) were considered to be independent variables, while particle size (Y1), percentage entrapment efficiency (Y2), and percentage drug release (Y3) were considered as responses. The solid lipid was glyceryl monostearate, while the surfactant was polysorbate 80. The optimized formulation has a particle size of 110.2 nm, % entrapment efficiency of 82.56%, and % drug release of 94.86%. The incompatibility of drug excipients was established by differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). Nasal histopathology tests on sheep mucosa revealed that the developed SLNs were safe to utilize for intranasal delivery with no toxicity. Ex vivo permeation investigations revealed that the flux and diffusion coefficients for RT solid lipid nanoparticles and RT solution were 3.378 g/cm² /h and 0.310-3 cm² /h, respectively. Stability studies demonstrated that the developed SLNs were stable when stored under various storage conditions. The viability and vitality of adopting a lipid particle delivery system for improved bioavailability via the intranasal route were also established in the in vivo pharmacokinetic investigations. According to the histopathological and pharmacokinetic investigations, the developed formulations were safe, non-lethal, efficient, and robust. These results suggest the potentiality provided by rivastigmine tartrate-loaded solid lipid nanoparticles for nasal delivery. [ABSTRACT FROM AUTHOR]

Basal forebrain cholinergic dysfunction, most likely linked with tau protein aggregation, is a characteristic feature of Alzheimer's disease (AD). Recent evidence suggests that tau protein is a putative target for the treatment of dementia, and the tau aggregation inhibitor, hydromethylthionine mesylate (HMTM), has emerged as a potential disease-modifying treatment. However, its efficacy was diminished in patients already receiving approved acetylcholinesterase inhibitors. In this study, we ask whether this negative interaction can also be mimicked in experimental tau models of AD and whether the underlying mechanism can be understood. From a previous age profiling study, 6-month-old line 1 (L1) tau transgenic mice were characterized by a severe reduction in several cholinergic markers. We therefore assessed whether long-term pre-exposure with the acetylcholinesterase inhibitor rivastigmine alone and in conjunction with the tau aggregation inhibitor HMTM can reverse cholinergic deficits in L1. Rivastigmine and HMTM, and combinations of the two compounds were administered orally for 11 weeks to both L1 and wild-type mice. The brains were sectioned with a focus on the basal forebrain, motor cortex and hippocampus. Immunohistochemical staining and quantification of choline acetyltransferase (ChAT), tyrosine kinase A (TrkA)-positive neurons and relative optical intensity (ROI) for vesicular acetylcholine transporter (VAChT), and acetylcholinesterase (AChE) reactivity confirmed reversal of the diminished cholinergic phenotype of interneurons (nucleus accumbens, striatum) and projection neurons (medial septum, nucleus basalis magnocellularis) by HMTM, to a greater extent than by rivastigmine alone in L1 mice. Combined administration did not yield additivity but, in most proxies, led to antagonistic effects in which rivastigmine decreased the benefits shown with HMTM alone. Local markers (VAChT and AChE) in target structures of the basal forebrain, motor cortex and hippocampal CA3 seemed to be normalized by HMTM, but not by rivastigmine or the combination of both drugs. HMTM, which was developed as a tau aggregation inhibitor, strongly decreased the tau load in L1 mice, however, not in combination with rivastigmine. Taken together, these data confirm a cholinergic phenotype in L1 tau transgenic mice that resembles the deficits observed in AD patients. This phenotype is reversible by HMTM, but at the same time appears to be subject to a homeostatic regulation induced by chronic pre-treatment with an acetylcholinesterase inhibitor, which interferes with the efficacy of HMTM. The strongest phenotypic reversal coincided with a normalization of the tau load in the cortex and hippocampus of L1, suggesting that tau accumulation underpins the loss of cholinergic markers in the basal forebrain and its projection targets. [ABSTRACT FROM AUTHOR]

The microneedle (MN) delivery system presents an attractive administration route for patients with Alzheimer's disease (AD). However, the passive drug delivery mode and low drug loading of MNs often result in unsatisfactory therapeutic efficiency. To address these dilemmas, we developed dual engine-drive bionic MNs for robust AD treatment. Specifically, free rivastigmine (RVT) and RVT particles were co-loaded within the MNs to construct the valve and chambers of the guava, respectively, which can serve as an active engine to promote drug permeation by generating capillary force. K 2 CO 3 and citric acid were introduced as a pneumatic engine into the MNs to promote the permeation of free RVT into deeper skin layers for early intervention in AD. Further, the RVT particles served as a drug depot to provide continuous drug release for prolonged AD treatment. Compared with free RVT-loaded MNs, the dual engine-driven bionic MNs showed an increase in drug loading, cumulative transdermal permeability, and normalized bioavailability of approximately 40%, 22%, and 49%, respectively. Pharmacodynamic studies further confirmed that the dual engine-driven bionic MNs were most effective in restoring memory and recognition functions in mice with short-term memory dysfunction. Therefore, the dual engine-driven bionic MNs hold great promise for highly efficient AD treatment. [Display omitted] • Bionic MNs driven with dual pneumatic and capillary forces significantly enhanced the drug loading and bioavailability of rivastigmine. • Bionic MNs with biphasic drug release behavior provided early intervention and prolonged treatment of Alzheimer's disease. • Bionic MNs effectively restored the memory and recognition functions of mice. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a brain illness that causes cognitive impairment in the elderly, especially females, as a result of genetics, hormones, and life experiences. It becomes more severe with age and is associated with cardiovascular disease, hypertension, and diabetes. Beta-amyloid plaques and hyper phosphorylated Tau protein buildup are common clinical findings. Misfiling of amyloid precursor protein (APP) and Amyloid beta peptide (Aβ) proteins contributes to Alzheimer's disease. Enzyme Acetylcholinesterase enzyme interacts with amyloid-beta, enhancing its accumulation in insoluble plaques, leading to successful treatment for Alzheimer's disease primarily based on lowering this enzyme. Treatments include using the Rivastigmine for mild, moderate, or severe Alzheimer's disease, which inhibits acetylcholinesterase, but may cause side effects; Solanine derivatives, nightshade toxin, it is cholinesterase inhibitory, may mitigate Alzheimer's illness is progressing. In this research utilized a molecular docking program, which is a computer's computational ability to determine the optimal position for a specific compound to bind to a protein or target, forming a target-ligand complex and displaying biological activity and aiding in the development of effective anti-AD treatments and understanding AD pathological mechanisms. The study examined complexes of 3LII (Acetylcholinesterase receptor) in the A and B chain with Solanine and Rivastigmine derivatives, using an in-silico approach. PyRx default sorter was used to improve docking accuracy. Four compounds were selected based on their higher binding affinities in chain A and B. The results showed that Solanine derivatives (alpha-Solanine, Beta1-Solanine and Beta2-Solanine) have higher binding strength (−9.0,-9.3 and −8.6) than Rivastigmine (−7.2) in chain A, and also the binding strength was high for the Solanine derivatives (alpha-Solanine, Beta1-Solanine, and Beta2-Solanine) (−9.0,-8.8 and −8.9) is higher than Rivastigmine (−6.0) in the chain B. Solanine derivatives showed higher binding strength with acetylcholinesterase, potentially for to reduce the progression of the disease.

In clinical trials for Alzheimer’s disease (AD), hydromethylthionine mesylate (HMTM) showed reduced efficacy when administered as an add-on to symptomatic treatments, while it produced a significant improvement of cognitive function when taken as monotherapy. Interference of cholinesterase inhibition with HMTM was observed also in a tau transgenic mouse model, where rivastigmine reduced the pharmacological activity of HMTM at multiple brain levels including hippocampal acetylcholine release, synaptosomal glutamate release and mitochondrial activity. Here, we examined the effect of HMTM, given alone or in combination with the acetylcholinesterase inhibitor, rivastigmine, at the level of expression of selected pre-synaptic proteins (syntaxin-1; SNAP-25, VAMP-2, synaptophysin-1, synapsin-1, α-synuclein) in brain tissue harvested from tau-transgenic Line 1 (L1) and wild-type mice using immunohistochemistry. L1 mice overexpress the tau-core unit that induces tau aggregation and results in an AD-like phenotype. Synaptic proteins were lower in hippocampus and cortex but greater in basal forebrain regions in L1 compared to wild-type mice. HMTM partially normalised the expression pattern of several of these proteins in basal forebrain. This effect was diminished when HMTM was administered in combination with rivastigmine, where mean protein expression seemed supressed. This was further confirmed by group-based correlation network analyses where important levels of co-expression correlations in basal forebrain regions were lost in L1 mice and partially re-established when HMTM was given alone but not in combination with rivastigmine. These data indicate a reduction in pharmacological activity of HMTM when given as an add-on therapy, a result that is consistent with the responses observed in the clinic. Attenuation of the therapeutic effects of HMTM by cholinergic treatments may have important implications for other potential AD therapies.

Alzheimer’s disease (AD) is a neurodegenerative disorder. Although the first case of Alzheimer’s disease was recorded over a century ago, the etiology of the disease remains unknown. There are several hypotheses regarding the process of neurodegeneration, however, it is impossible to provide a specific cause of Alzheimer’s disease in humans, due to the lack of in vivo models. Only a few specific changes in the body occurring in the course of this disease have been described so far, and no effective drugs have been developed to stop its progression. The effect of the currently used drugs is limited only to improving the cognitive functions and general patients’ well-being. Four medicinal substances have been approved for the treatment of Alzheimer's disease so far, namely, donepezil, rivastigmine, galantamine, and memantine. In this article, a brief description of marketed drugs used for the treatment of Alzheimer's disease is presented as well as selected substances in phase III clinical trials. Moreover, a strategy of multifunctional ligands along with a description of the activity of selected compounds containing in their structure a moiety of one of the drugs used in the treatment of Alzheimer’s disease, namely, donepezil, rivastigmine, or galantamine, is presented in the paper. Selected compounds synthesized over the last five years are described. Taking into account the multifactorial nature of Alzheimer's disease, the multifunctional ligands strategy directed at more than one biological target is used by many research groups. A large group of multi-target ligands is based on derivatives containing in their structure a moiety of selected acetylcholinesterase inhibitors. These moieties are combined with various types of compounds with known biological activity. As a result, derivatives with multi-target effects are obtained, mainly cholinesterase inhibitory properties and inhibition of the β-amyloid aggregation process, as well as antioxidant and neuroprotective effects.

Abstract Background To assess the effectiveness, safety, and tolerability of anti-Alzheimer agents (memantine, galantamine, rivastigmine, and donepezil) in controlling ADHD symptoms in children, adolescents, and adults. Methods Following the PRISMA guideline, clinical trials assessing the potency of anti-Alzheimer medications in managing ADHD symptoms were imported from PubMed, Web of Science, and Scopus (until February 2023). Screening stages were conducted by two independent researchers. Two independent researchers also extracted data from clinical trials reporting the outcomes as the reduction in scores of ADHD questionnaires. The risk of bias within the included studies was assessed using the Cochrane Collaboration tool, while the certainty of outcomes was evaluated based on the GRADE criteria. Results Of the initial 1597 studies, 11 studies were included. No studies were available for rivastigmine, and only a single study was conducted for galantamine. The results of the other two medications had a slight inconsistency. While both memantine and donepezil were reported to be effective in several studies, they were reported to be ineffective in some other studies. Side effects were mostly reduced appetite and headache. The tolerability of memantine, donepezil, and galantamine was all convincing. Conclusions While galantamine did not demonstrate a promising efficacy in ADHD, memantine and donepezil showed effectiveness. However, future studies are needed to confirm their efficacy in ADHD since there was some inconsistency.

Objective: To evaluate the efficacy and safety of Chinese herbal medicines (CHMs) combined with chemical drugs for the treatment of Alzheimer's disease (AD). Materials and Methods: Databases were searched to retrieve randomized controlled trials (RCTs) of CHMs combined with tacrine, galantamine, rivastigmine, donepezil, or memantine, following strict inclusion and exclusion criteria. Only research papers published in English, Chinese, and Japanese were considered. The primary outcome was the mini-mental state examination (MMSE) score and the secondary outcomes were AD assessment scale cognitive subscale (ADAS-Cog) score and safety evaluation. Meta-analysis was carried out using RevMan 5.3 and subgroup analysis was conducted to identify the sources of heterogeneity. Results: A total of 15 RCTs with 1386 participants were included in this study. Only donepezil was used in the retrieved literature. Meta-analyses showed that the combination of CHMs with donepezil led to significant improvement in the MMSE score (Z = 9.45; P < 0.00001; weighted mean difference [WMD] =2.68, 95% confidence interval [CI]: 2.12–3.24) and a significant decrease in the ADAS-Cog score (Z = 5.53; P < 0.00001; WMD = −3.79; 95% CI: −5.13–−2.44). Safety evaluation demonstrated that these combination treatments relieved adverse events such as insomnia (risk ratio [RR] =0.20, 95% CI: 0.06–0.68; P = 0.01) and hive (RR = 0.10; 95% CI: 0.01–0.73; P = 0.02). Conclusions: The combination of CHMs with a chemical drug like donepezil led to significant improvements in patient cognition as well as a better safety profile when compared to the application of a chemical drug alone.

Background: To assess the effectiveness, safety, and tolerability of anti-Alzheimer agents (memantine, galantamine, rivastigmine, and donepezil) in controlling ADHD symptoms in children, adolescents, and adults. Methods: Following the PRISMA guideline, clinical trials assessing the potency of anti-Alzheimer medications in managing ADHD symptoms were imported from PubMed, Web of Science, and Scopus (until February 2023). Screening stages were conducted by two independent researchers. Two independent researchers also extracted data from clinical trials reporting the outcomes as the reduction in scores of ADHD questionnaires. The risk of bias within the included studies was assessed using the Cochrane Collaboration tool, while the certainty of outcomes was evaluated based on the GRADE criteria. Results: Of the initial 1597 studies, 11 studies were included. No studies were available for rivastigmine, and only a single study was conducted for galantamine. The results of the other two medications had a slight inconsistency. While both memantine and donepezil were reported to be effective in several studies, they were reported to be ineffective in some other studies. Side effects were mostly reduced appetite and headache. The tolerability of memantine, donepezil, and galantamine was all convincing. Conclusions: While galantamine did not demonstrate a promising efficacy in ADHD, memantine and donepezil showed effectiveness. However, future studies are needed to confirm their efficacy in ADHD since there was some inconsistency. [ABSTRACT FROM AUTHOR]

Efficient drug delivery remains a critical challenge for treating neurodegenerative diseases, such as Alzheimer's disease (AD). Using innovative nanomaterials, delivering current medications like acetylcholinesterase inhibitors to the brain through the intranasal route is a promising strategy for managing AD. Here, we developed a unique combinational drug delivery system based on N,N,N-trimethyl chitosan nanoparticles (NPs). These NPs encapsulate rivastigmine, the most potent acetylcholinesterase inhibitor, along with insulin, a complementary therapeutic agent. The spherical NPs exhibited a zeta potential of 17.6 mV, a size of 187.00 nm, and a polydispersity index (PDI) of 0.29. Our findings demonstrate significantly improved drug transport efficiency through sheep nasal mucosa using the NPs compared to drug solutions. The NPs exhibited transport efficiencies of 73.3% for rivastigmine and 96.9% for insulin, surpassing the efficiencies of the drug solutions, which showed transport efficiencies of 52% for rivastigmine and 21% for insulin ex vivo. These results highlight the potential of a new drug delivery system as a promising approach for enhancing nasal transport efficiency. These combinational mucoadhesive NPs offer a novel strategy for the simultaneous cerebral delivery of rivastigmine and insulin, which could prove helpful in developing effective treatments of AD and other neurodegenerative conditions. [ABSTRACT FROM AUTHOR]

Background and purpose: Neuropsychiatric symptoms including depression, apathy and psychosis occur frequently in patients with Parkinson's disease. A subgroup of patients develop cognitive impairment, which may increase the risk of falls due to reduced attention. The acetylcholinesterase inhibitor rivastigmine is beneficial in Parkinson's disease dementia, but whether the use of rivastigmine is effective earlier in the disease course is unclear. The aim of this systematic review was to assess the evidence for rivastigmine in the treatment of neuropsychiatric symptoms in Parkinson's disease without dementia. Methods: Embase, Medline, PsychINFO, Cochrane CENTRAL, NGLC, National Institute for Health and Care Excellence Evidence and medRxiv.org were searched for studies with terms relating to population (Parkinson's disease) and intervention (rivastigmine). Of 1922 references identified, 358 were duplications. Following title and abstract review, 1331 articles were excluded. After full‐text review, nine articles remained. Results: Outcomes were heterogenous, therefore, the results are presented in narrative form. The articles included six randomized controlled trials, two open‐label trials and one case series. Outcome measures included: time to develop psychosis; frequency of rapid eye movement sleep behaviour disorder (RBD) episodes; apathy; gait variability; falls; cognitive ability; Neuropsychiatric Inventory score; and regional spontaneous brain activity. Conclusions: There is evidence that rivastigmine is beneficial for RBD and apathy in Parkinson's disease patients without dementia. There is high level evidence that rivastigmine reduces falls, which may be due to improved attention. The impact of rivastigmine on psychotic symptoms is less clear, but is supported by current theoretical models which involve acetylcholine dysfunction in the generation of visual hallucinations in Parkinson's disease. [ABSTRACT FROM AUTHOR]

Anticholinergic agents are commonly taken in overdose, often causing delirium. The spectrum of anticholinergic delirium ranges from mild agitation to severe behavioural disturbance. Physostigmine is an effective treatment for anticholinergic delirium, but its availability is limited. As rivastigmine is readily available, it has been used to manage anticholinergic delirium; however, there is limited research investigating its use. This was a retrospective review of patients with anticholinergic delirium treated in two toxicology units with rivastigmine (oral capsule or transdermal patch) from January 2019 to June 2023. The primary outcome was the use of further parenteral treatment (sedation or physostigmine) for delirium post rivastigmine administration. Fifty patients were administered rivastigmine for the management of anticholinergic delirium. The median age was 36 years (interquartile range: 25–49 years) and 27 (54 per cent) were females. Features consistent with anticholinergic toxicity included tachycardia in 44 (88 per cent) and urinary retention requiring catheterisation in 40 (80 per cent). Forty-three patients (86 per cent) were treated with physostigmine before rivastigmine administration. Twenty-two were managed with transdermal rivastigmine (most commonly 9.5 mg/24 hour patch), and 28 with oral rivastigmine 6 mg. Further parenteral sedation and/or physostigmine treatment were required more often in patients given transdermal than oral rivastigmine [16/22 (73 per cent) versus 9/28 (32 per cent), P = 0.010)]. No patients had bradycardia or gastrointestinal symptoms following rivastigmine administration. One patient with a history of epilepsy had a seizure, 1.5 hours post physostigmine administration and 7 hours post transdermal rivastigmine. Rivastigmine has been increasingly used for the management of patients with anticholinergic delirium, due to the lack of availability of physostigmine. In this case series, rivastigmine transdermal patch appeared to be less effective than oral rivastigmine capsules, likely due to its slow onset of action and/or insufficient dose. Rivastigmine can be used to treat anticholinergic delirium. In our case series oral rivastigmine appeared more effective than transdermal rivastigmine. [ABSTRACT FROM AUTHOR]

Objective: Cholinesterase inhibitor (ChEIs) is the first-line drug for Alzheimer's disease (AD). Understanding torsade de pointes (TdP)/QT prolongation with different ChEIs is essential for its safe and rational administration. This study aimed to evaluate the correlation between different ChEIs and TdP/QT prolongation. Methods: All ChEIs related TdP/QT prolongation cases were retrieved from the FAERS database using standard MedDRA query (SMQ) from the first quarter of 2004 to the third quarter of 2022. Disproportionality and sensitivity analysis were used to determine the signal of TdP/QT prolongation related to ChEIs. Results: 557 cases of TdP/QT prolongation related to 3 ChEIs were searched by SMQ. The patients were mostly elderly people, with markedly more female than male. The signals of TdP/QT prolongation for ChEIs were detected by disproportionality analysis, and the signal of Donepezil was the strongest. The sensitivity analysis results indicate a robust and stable correlation between these signals with ChEIs. TdP/QT prolongation usually occurs within 1 month after taking ChEIs. The drug with the highest frequency of combination with donepezil and galantamine is citalopram, and the drug with the highest frequency of combination with rivastigmine is atorvastatin. Conclusion: The signals of TdP/QT prolongation related to ChEIs were strong and stable. It is necessary to be vigilant about the TdP/QT prolongation of various ChEIs, especially in elderly women, the initial stage after taking ChEIs, and when ChEIs combining with drugs that could prolong the QT interval. [ABSTRACT FROM AUTHOR]

Background: The present study aims to develop an Elementary Osmotic tablet (EOP) of Rivastigmine Hydrogen Tartrate (RHT). EOP consists of a core tablet suitably coated with a polymeric solution, and an orifice drilled on one side of the tablet. Materials and Methods: The influence of core variables, including sodium chloride (osmogen) concentration and Polyvinyl Pyrrolidine K30 (PVP K30) concentration, have been investigated and optimized by factorial design. The effect of membrane (coating) variables, including polyethylene glycol 400 (PEG 400) amount and percent coating weight gain have been studied. The rivastigmine release of the optimized system has been investigated in various dissolution media, at different stirring rates, at variable pH, and variable osmotic pressure. Results: It was observed that PEG 400 incorporated in the coating membrane improved drug release. The sodium chloride had a profoundly positive influence, and PVP K30 had a negative influence on the rivastigmine release. The finding reveals that the core tablet containing sodium chloride (50 mg) and PVP K30 (2.5 mg) coated with the solution containing 20% PEG 400 and 5% weight gain was optimized. Conclusion: The developed EOP provides the RHT release for up to 24 hr with improved bioavailability. The results instigated a controlled release of rivastigmine. [ABSTRACT FROM AUTHOR]

Selective butyrylcholinesterase inhibitors are considered promising drug candidates for the treatment of Alzheimer's disease. In this work, one rivastigmine–bambuterol hybrid (MTR-1) and fourteen of its analogues were synthesized, purified, and characterized. In vitro cholinesterase assays showed that all the compounds were more potent inhibitors of BChE when compared to AChE. Further investigations indicated that MTR-3 (IC50(AChE) > 100,000 nM, IC50(BChE) = 78 nM) was the best compound in the series, showing high butyrylcholinesterase selectivity and inhibition potency, the potential to permeate the blood–brain barrier, and longer-lasting BChE inhibition than bambuterol. These compounds could be used to discover novel specific BChE inhibitors for the treatment of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Rivastigmine is an acetylcholinesterase (AchE) and butyrylcholinesterase (BchE) inhibitor drug approved by the US Food and Drug Administration (FDA) for the treatment of mild to moderate dementia of Alzheimer's type. However, its first-pass metabolism and gastrointestinal side effects negatively affect the tolerability and efficacy of oral therapy. These adverse effects could be avoided with the use of a sustained -release formulation as an intramuscular (IM) administration system. The objective of this work was to develop polylactic co-glycolic acid (PLGA) microparticles for the sustained release of rivastigmine and to evaluate its stability during storage, tissue tolerance, in vitro release, and in vivo pharmacokinetics after its IM administration. The microparticles were made by the solvent evaporation emulsion method. A series of formulation parameters (the type of polymer used, the amount of polymer used, the initial amount of rivastigmine, and the volume of PVA 0.1% w/v) were studied to achieve an encapsulation efficiency (EE) and a rivastigmine load of 54.8 ± 0.9% and 3.3 ± 0.1%, respectively. The microparticles, whose size was 56.1 ± 2.8 μm, had a spherical shape and a smooth surface. FT-IR analysis showed that there is no chemical interaction between rivastigmine and the polymer. PLGA microparticles maintain rivastigmine retained and stable under normal (5 ± 3 °C) and accelerated storage (25 ± 2 °C and 60 ± 5 % RH) conditions for at least 6 months. The microparticles behaved as a sustained release system both in vitro and in vivo compared to non-encapsulated rivastigmine. The IM administration of the formulation in rats did not produce significant tissue damage. However, it is necessary to reproduce the experiments with multiple doses to rule out a negative effect in terms of tolerability in chronic treatment. To the best of our knowledge, this study is the only one that has obtained the sustained release of rivastigmine from PLGA microparticles after IM administration in an in vivo model. [Display omitted] [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive age‐related neurodegenerative brain disorder, which leads to loss of memory and other cognitive dysfunction. The underlying mechanisms of AD pathogenesis are very complex and still not fully explored. Cholinergic neuronal loss, accumulation of amyloid plaque, metal ions dyshomeostasis, tau hyperphosphorylation, oxidative stress, neuroinflammation, and mitochondrial dysfunction are major hallmarks of AD. The current treatment options for AD are acetylcholinesterase inhibitors (donepezil, rivastigmine, and galantamine) and NMDA receptor antagonists (memantine). These FDA‐approved drugs mainly provide symptomatic relief without addressing the pathological aspects of disease progression. So, there is an urgent need for novel drug development that not only addresses the basic mechanisms of the disease but also shows the neuroprotective property. Various research groups across the globe are working on the development of multifunctional agents for AD amelioration using different core scaffolds for their design, and carbamate is among them. Rivastigmine was the first carbamate drug investigated for AD management. The carbamate fragment, a core scaffold of rivastigmine, act as a potential inhibitor of acetylcholinesterase. In this review, we summarize the last 10 years of research conducted on the modification of carbamate with different substituents which primarily target ChE inhibition, reduce oxidative stress, and modulate Aβ aggregation. [ABSTRACT FROM AUTHOR]

Purpose: Due to impairments in memory and judgment, it is difficult for dementia patients to understand why they need medicine. Moreover, they often have swallowing difficulties. In this investigation, an oral dissolving film of rivastigmine tartrate (RT-ODF) was developed, offering a unique and convenient formulation for dementia patients. Methods: RT-ODF was developed using a solvent-casting technique. Sodium alginate and sodium carboxymethyl cellulose were used as film-forming polymers, and glycerol was used as a plasticizer. A full factorial design (32) was employed to estimate the impact of two factors at three levels: polymer concentration (1, 1.5, and 2% w/v) and plasticizer concentration (30, 40, and 50% w/v) on the responses, i.e., the tensile strength (TS), the disintegration time (DT), and the quantity of drug released (Q10 min). Results: The optimized formula (A1) that had the highest desirability value (0.923) exhibited the lowest tensile strength (3.67 ± 0.72 MPa), the shortest disintegration time (20 ± 2.0 s), and the highest percentage of drug released after 10 min (97.12 ± 2.01%). It was composed of 1% w/v sodium alginate (ALG-Na) and plasticized with 30% w/v glycerol. The pharmacokinetic study revealed that the RT-ODFs enhanced the drug's bioavailability by 1.91-fold relative to the reference product (Exelon® capsule). Conclusion: Oral dissolving films of rivastigmine tartrate could be a promising approach to promote drug bioavailability and convenience for geriatric patients. [ABSTRACT FROM AUTHOR]