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The purpose of this research was to prepare and evaluate monolithic drug-in-adhesive type patches of Rasagiline Mesylate (RM) containing penetration enhancer and having seven day wear property. Preformulation studies like solubility in permeation enhancers, compatibility study, transmission study, uptake study and crystallization study of Rasagiline Mesylate in various pressure sensitive adhesive polymers were performed. Transdermal system was prepared by solvent casting method. The effects of various permeation enhancers (Propylene Glycol, Oleic Acid, Isopropyl Palmitate, and lauryl lactate) on the ex-vivo transcutaneous absorption of Rasagiline Mesylate through human cadaver skin were evaluated by modified Franz diffusion cell system. Ex-vivo transcutaneous absorption of prepared transdermal patch was performed using different concentration of Lauryl lactate (3%, 5%, and 7%). In-vitro Adhesion testing (Peel, tack shear etc.) was performed on different dry GSM (Grams per Square Meter) of patch like 80GSM, 100 GSM and 150 GSM. The final transdermal patches were tested for appearance, weight of matrix, thickness, % assay of drug content, in-vitro adhesion testing, cold flow study and ex-vivo skin permeation studies. Based on crystallization study and adhesion testing, Durotak-4098 (14% drug concentration) was selected as pressure sensitive adhesive. Patch containing Lauryl lactate showed highest cumulative permeation compared to other permeation enhancers. The patch containing 5% laurel lactate showed greater transdermal flux (2.36 µg/cm2 /hr). Patch with 150 dry GSM showing promising adhesion properties. Backing film Scotchpak 9723 and release liner Saint Gobain 8310 was selected based on transmission and uptake study of Rasagiline Mesylate. Stability study indicates that developed formulation remains stable. In conclusion, the present research confirms the practicability of developing Rasagiline Mesylate transdermal system.
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A novel reversed phase-high-performance liquid chromatography (HPLC) method for the estimation of rasagilinemesylate (RM), a potent anti-Parkinson drug in Active Pharmaceutical Ingredient (API), and tablet dosage form wasdeveloped and validated in the present research. HPLC instrument (Shimadzu) comprises ultraviolet detector andphenomenex 100 C18 (250 × 4.6 mm, 5 µm) column was utilized in the study. A mixture of acetonitrile and waterin the ration of 50:50, adjusted to pH 3.0 ± 0.05 with ortho-phosphoric acid was used as the mobile phase. Thechromatographic conditions; flow rate 0.8 ml/minute, run time 6.0 minutes, injection volume 50 µl, and detectionwavelength 268 nm were maintained during the study at room temperature. To ensure performance of novel methoddeveloped, it was validated according to International conference on harmonization guidelines. The developed methodwas subjected to the forced degradation studies to find out the stability indicating nature of the method by quantifyingthe RM in presence of its degradation products and the peaks which were responsible for the degraded products werenot interfered with the API principle peak. The proposed stability indicating newly developed and validated methodcan be adopted for the quantification of RM in bulk and pharmaceutical formulations.
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OBJECTIVE: To establish a determination method of trace hydroxylamine in rasagiline mesylate by ion chromatography with on line SPE. METHODS: First, the sample was injected and hydroxylamine was transferred to the analytical column, and the matrix of rasagiline mesylate was trapped on the SPE column, IonPac CG12A. Second, the IonPac CG12A column was washed with acetonitrile and equipped with MSA solution of the same concentration as eluent. RESULTS: The liner calibration curve was obtained over the range of 0.04-3.75 μg·mL-1with a correlation coefficient (r2) of 0.999 9. And the detection limit of hydroxylamine was 0.02 μg·mL-1. The method was applied to detect trace hydroxylamine in rasagiline mesylate samples successfully. The spiked recoveries were 94%-103%. CONCLUSION: The method has high automation degree, selectivity and sensitivity for trace hydroxylamine analysis.
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The present study was to prepare and characterize Rasagiline mesylate loaded nanoscale solid lipid particles and evaluate its In-vitro release. Rasagiline mesylate loaded solid lipid nanoparticles was fabricated by microemulsion technique and then characterized with respect to particle size, polydispersity index and zeta potential were measured by photon correlation spectroscopy. Morphological examination was visualized by transmission electron microscopy. The release of Rasagiline mesylate from solid lipid nanoparticles was performed by using the incubator shaking technique. The fabricated formulations particle size ranged from 160.20±3.2 to 210.12±5.3 nm and the zeta potential measurements indicates a narrow size distribution. The Polydispersity index values shown narrow that means the nanoparticles are homogenous in nature. Drug loading and entrapment efficiency of RMSLN-I & RMSLN-II were 33.34±1.45 % & 76.24±1.2 % and 16.67±0.86 % & 73.75±1.02 %, respectively. TEM revealed the particles were monodisperse, uniform size and quasispherical shape. Release of Rasagiline mesylate loaded nanoscale solid lipid particles were shown efficient prolonged drug release and followed by Fickian diffusion mechanism. Furthermore, RM loaded SLNs were found to be stable, after 6 months of storage at different conditions. The developed solid lipid nanoparticles were able to control the drug release for a prolonged period of time.
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@#This study aimed at investigating the neuroprotective effect and behavior improvement of rasagiline on 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine(MPTP)model mice of Parkinson′s disease. The tyrosine hydroxylase(TH)-positive dopaminergic neurons in substantia nigra were observed by immunocytochemistry. HPLC-ECD was used to detect the dopamine and its metabolite levels. Western blot was used to examine the protein expression of TH. The results showed that the mice appeared a series of acute behavior change after the injection of MPTP. Rasagiline(20 mg/kg)exerted significant protection against MPTP-induced loss of TH-positive dopaminergic neurons. The TH-positive neurons in rasagiline-treated mice brain increased significantly compared with those of MPTP-treated group. Rasagiline also enhanced dopamine and its metabolite levels in striatum significantly. In conclusion, rasagiline has protective effect on the acute mouse model of MPTP-induced Parkinsonism.
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Aim To develop LC-MS/MS method to de-termine rasagiline mesylate in human plasma and its application in a pharmacokinetics study .Methods Plasma samples were extracted using liquid-liquid ex-traction with clopidogrel as internal standard .The con-tent of rasagiline mesylate in human plasma was detec-ted by selectivelypositive ion reaction monitoring on a triple quadrupoles tandem mass spectrometer .The de-tected ions were m/z 172.3→117.1 ( rasagiline ) , m/z 322.3 →184.0 ( clopidogrel ) .The linear calibration curve was obtained in the concentration range of 0.1047~20.93 μg · L-1 .The lower limit of quantifi-cation was 0.1047 μg · L-1 .Indicators of the method validation were in line with requirements .The method was used to determine the concentration of rasagiline in human plasma after oral administration of rasagiline mesylate capsule to 24 healthy Chinese volunteers ( with half males and females ) and the results were compared statistically .Results The single oral dose of 0.5 ,1.0 and 2.0 mg presented linear pharmacokinetics in the health volunteers .No accumulation was observed with multiple doses .Meanwhile , no significant difference was identified between the gender groups . High fat postprandial has obvious effects on the peak serum con-centration of rasagiline , but there was no effect on the absorption amount and cumulative excretion .Conclu-sion The LC-MS/MS method is specific and sensi-tive, and can be successfully applied to the pharmaco-kinetic study of Rasagiline mesylate tablets in healthy Chinese volunteers .
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A simple RP-HPLC method for the determination of Rasagiline Mesylate in bulk and tablet dosage form was devel-oped. Numerous HPLC conditions were tested for determination of rasagiline. The best result was achieved by using Purosphere star RP-18, (150×4.6mm), 5μm column and a mobile phase consisting of Potassium Orthophosphate: Acetonitrile (60:40 v/v) adjusted to pH 7.0(±0.05) with Ammonia solution, a flow rate of 1.5 ml/min with ultraviolet detection at 210nm. The correlation coefficients for calibration curves within the detection range of 5-30μg/ml were 0.9993. The within and between-day precision was determined for both retention time and peak area. The retention time of rasagiline is 6.0 minutes.
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A simple RP-HPLC method for the determination of Rasagiline Mesylate in bulk and tablet dosage form was devel-oped. Numerous HPLC conditions were tested for determination of rasagiline. The best result was achieved by using Purosphere star RP-18, (150×4.6mm), 5μm column and a mobile phase consisting of Potassium Orthophosphate: Acetonitrile (60:40 v/v) adjusted to pH 7.0(±0.05) with Ammonia solution, a flow rate of 1.5 ml/min with ultraviolet detection at 210nm. The correlation coefficients for calibration curves within the detection range of 5-30μg/ml were 0.9993. The within and between-day precision was determined for both retention time and peak area. The retention time of rasagiline is 6.0 minutes.
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INTRODUCTION: Parkinson's disease (PD) is a second most common neurodegenerative disorder which affects 1 % to 2% of people older than 60 years and is characterized by cardinal features of bradykinesia, rigidity, and rest tremor (2). Most of the motor disability experienced by patients results from progressive loss of dopaminergic neurons of the Substantia Nigra pars compacta (SNpc). However, recent studies have shown that PD is also associated with extensive non-dopaminergic pathology. Recent trend in the treatment of PD include development of new drugs that will not only address the symptom relief but will also ameliorate the progression of dopaminergic neuron degeneration (3).OBJECTIVE: To assess the evidence from randomized controlled trials the effects of Rasagiline compared with placebo in the treatment of patients with Parkinson's diseaseDESIGN: Meta-analysis of 3 randomized trials identified through Medline/Pubmed and Cochrane Library. Summary of the outcome variables was computed using difference of two means of the United Parkinson's disease rating scale (UPDRS) score and their corresponding standard error of the means under fixed effects models. The chi-square test was done to test heterogeneity. Statistical analysis was done using Revman version 5.RESULTS: The sample size of the studies ranged from 13 to 595 patients. The mean age of the trial participants were in the 60s with a relatively narrow standard deviation. All studies were randomized and placebo controlled. The main outcome measure was change in the UPDRS score from baseline. The mean difference between Rasagiline 1 mg and placebo is -3.06 (95% CI -3.81, -2.31) and Rasagiline 2mg and placebo is -3.17 (95% CI -3.92, -2.42). The overall effect was statistically significant (z=8.01; pCONCLUSION: Based on this meta-analysis, Rasagiline is effective as monotherapy in early Parkinson's disease.
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Humanos , Neurônios Dopaminérgicos , Hipocinesia , Indanos , Rigidez Muscular , Degeneração Neural , Doença de Parkinson , Parte Compacta da Substância Negra , TremorRESUMO
Monoamine oxidase inhibitors (MAO-I) belong to the earliest drugs tried in Parkinson's disease (PD). They have been used with or without levodopa (L-DOPA). Non-selective MAO-I due to their side-effect/adverse reaction profile, like tranylcypromine have limited use in the treatment of depression in PD, while selective, reversible MAO-A inhibitors are recommended due to their easier clinical handling. For the treatment of akinesia and motor fluctuations selective irreversible MAO-B inhibitors selegiline and rasagiline are recommended. They are safe and well tolerated at the recommended daily doses. Their main differences are related to (1) metabolism, (2) interaction with CYP-enzymes and (3) quantitative properties at the molecular biological/genetic level. Rasagiline is more potent in clinical practise and has a hypothesis driven more favourable side effect/adverse reaction profile due to its metabolism to aminoindan. Both selegiline and rasagiline have a neuroprotective and neurorestaurative potential. A head-to head clinical trial would be of utmost interest from both the clinical outcome and a hypothesis-driven point of view. Selegiline is available as tablet and melting tablet for PD and as transdermal selegiline for depression, while rasagiline is marketed as tablet for PD. In general, the clinical use of MAO-I nowadays is underestimated. There should be more efforts to evaluate their clinical potency as antidepressants and antidementive drugs in addition to the final proof of their disease-modifying potential. In line with this are recent innovative developments of MAO-I plus inhibition of acetylcholine esterase for Alzheimer's disease as well as combined MAO-I and iron chelation for PD.
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Acetilcolina , Doença de Alzheimer , Antidepressivos , Depressão , Congelamento , Manobra Psicológica , Cabeça , Indanos , Ferro , Levodopa , Moclobemida , Monoaminoxidase , Inibidores da Monoaminoxidase , Doença de Parkinson , Fenelzina , Selegilina , TranilciprominaRESUMO
An isocratic stability indicating liquid chromatographic method has been developed and validated for the determination of Rasagiline in bulk drug and its pharmaceutical dosage forms. Separation of the drug with degradation products was achieved using Puroshere Star, C18, 150 x 4.6mm; 5μm column as stationary phase and pH 7.0(±0.05) buffer: Acetonitrile (40:60,v/v) as mobile phase at a flow rate of 1.0 mL/min. UV detection was performed at 210 nm. The method is linear over the range of 4.8 – 150.5 μg/mL. The percent recovery of drug in dosage forms was ranged from 98.0 to 102.1. The method is simple, rapid, precise, selective and stability indicating and can be used for the assay in quality control and stability studies samples.
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Parkinson's disease (PD) and Alzheimer's Disease (AD) are severe neurodegenerative disorders, with no drugs that are currently approved to prevent the neuronal cell loss characteristic in brains of patients suffering from PD and AD and all drug treatment are synptomactic. Due to the complex pathophysiology, including a cascade of neurotoxic molecular events that results in neuronal death and predisposition to depression and eventual dementia and etiology of these disorders, an innovative approach towards neuroprotection or neurorestoration (neurorescue) may be the development and use of multifunctional pharmaceuticals. Such drugs target an array of pathological pathways, each of which is believed to contribute to the cascades that ultimately lead to neuronal cell death. In this short review, we discuss examples of novel multifunctional ligands that may have potential as neuroprotective-neurorestorative therapeutics in PD and AD. The compounds discussed originate from synthetic chemistry as well as from natural sources.