Intranasal thermosensitive gel for rasagiline mesylate (RM) was developed for effective treatment of Parkinson's disease. Intranasal gels were prepared by combination of poloxamer 407 and poloxamer 188 (1:1) with mucoadhesive polymers (carbopol 934 P and chitosan). The formulations were evaluated for sol-gel transition temperature, in-vitro drug release and in-vivo mucociliary transit time. Further, optimal intranasal gel formulations were tested for in-vivo pharmacokinetic behavior, nasal toxicity studies and brain uptake studies. It was found that optimal formulations had acceptable gelation temperature (28-33 °C) and adequate in-vitro drug release profile. Pharmacokinetic study in rabbits showed significant (p < 0.05) improvement in bioavailability (four- to six-folds) of the drug from intranasal gels than oral solution. Chronic exposure studies in Wistar rats showed that these intranasal gels were non-irritant and non-toxic to rat nasal mucosa. Estimation of RM in rat brain tissue showed significant (p < 0.01) improvement in uptake of RM form intranasal gel formulations than nasal solution.
A simple, rapid and sensitive reverse-phase liquid chromatographic method is developed and validated for estimation of rasagiline mesylate in different plasma matrices (rat, rabbit and human plasma). The method employs an isocratic elution technique with a Kromasil C18 column and has an optimized mobile phase composition of 10 mM ammonium acetate buffer-acetonitrile (40:60 v/v). The plasma samples displayed linear detector responses in the concentration range of 0.5-20 µg/mL in all plasma matrices when monitored at 265 nm using an ultraviolet detector. Because the simple protein precipitation method yields over 95% recovery of rasagiline mesylate from all plasma matrices, no internal standard was used in this method. A detailed validation study of the method proves the accuracy, precision and selectivity (in estimating rasagiline mesylate) in all plasma matrices. The drug is also stable under various processing and storage conditions in all plasma matrices, as evident from the study. The present method was applied to determine the drug-protein binding ratio in all the plasma matrices. The use of this method in determining pharmacokinetic parameters of rasagiline mesylate by non-compartmental analysis after oral dosing in rabbits is also discussed.
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