Microemulsion-based gel for the transdermal delivery of rasagiline mesylate: In vitro and in vivo assessment for Parkinson's therapy.

Rasagiline mesylate (RSM) is a selective and irreversible monoamine oxidase B inhibitor used for the treatment of Parkinson's disease (PD). However, its unfavorable biopharmaceutical properties, such as extensive degradation in the gastrointestinal tract and first-pass metabolism are responsible for its low oral bioavailability and suboptimal therapeutic efficacy. Here, we report the feasibility of delivering RSM via the transdermal route using RSM containing microemulsion-based gel (RSM-MEG) to achieve effective management of PD. Our in vitro skin permeation studies of RSM-MEG showed significantly higher (at least ~1.5-fold) permeation across rat skin compared to the conventional RSM hydrogel. Our skin irritation studies in rabbits showed that RSM-MEG is safe for transdermal application. Finally, using the rat model of rotenone-induced Parkinsonism, we demonstrated that the topical application of RSM-MEG was equally effective in reversing PD symptoms when compared to oral RSM therapy. Thus, our study confirmed the feasibility and potential of transdermal delivery of RSM via simple topical application of RSM-MEG, and this approach could be an alternative therapeutic intervention for the treatment of Parkinson's disease.

Colloidal soft nanocarrier for transdermal delivery of dopamine agonist: ex vivo and in vivo evaluation.

Ropinirole, an antiparkinsoism dopamine agonist, is used to treat Restless Legs Syndrome. However, orally it undergoes degradation in gastrointestinal tract and extensive first pass metabolism, resulting in its poor and variable bioavailability of the commercially available oral tablets. In the present investigation, soft nanocarriers, viz., microemulsion of ropinirole with the globule size of 160.2 ± 3.87 nm and zeta potential of -4.24 mV was explored for transdermal application. Transdermal drug delivery offers benefits such as sustained therapeutic plasma levels of drugs, avoidance of first pass effect, and improved patient compliance. In comparison to the hydrogel, the developed microemulsion enhanced the drug permeation across the rat skin and porcine ear skin by 3.5 and 2 folds, respectively. Further, the developed microemulsion antagonized the catalepsy in the haloperidol-induced catalepsy rat model by 10 folds as compared to the marketed tablets. Additionally, in rotenone induced Parkinsonism rat model, the microemulsion showed improvement in the motor function by 76% whereas the oral tablet showed only 5% restoration of the normal function. Besides this, the developed formulation successfully restored the catalase and superoxide dismutase levels which were significantly reduced by rotenone administration. Overall, the in vivo studies suggested the potential of the developed transdermal microemulsion of Ropinirole as a viable alternative to marketed formulations.