ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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 .
ABSTRACT
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.