Department of Pharmacy
Permanent URI for this collectionhttp://localhost:4000/handle/123456789/1931
Browse
3 results
Search Results
Item Nose-to-brain delivery of rotigotine redispersible nanosuspension: In vitro and in vivo characterization(Elsevier, 2023-01) Pandey, Murali MonoharRotigotine (RTG) is an anti-Parkinson's drug approved by the USFDA to treat motor and non-motor symptoms of both early and advanced stages of the disease. However, issues like poor aqueous solubility, low oral bioavailability (<1%), first-pass metabolism, low systemic bioavailability (∼37%) and low brain bioavailability demean the therapy. This work developed poloxamer-stabilized RTG-Nanosuspension for intranasal (i.n.) administration. RTG-Nanosuspension was optimized using Box-Behnken design with critical variables affecting the responses, viz. particle size and PDI. The optimized RTG-Nanosuspension showed mean particle size of 73 nm and PDI of 0.286. Lyophilized RTG-Nanosuspension was also characterized for drug crystallinity, interactions, and morphology. The lyophilized RTG-Nanosuspension showed good stability and was a porous structure. The first 15 min of in vitro dissolution showed 95% cumulative drug dissolved from RTG-Nanosuspension formulation. RTG-Nanosuspension showed 20-fold increase in nasal permeation. The nasal ciliotoxicity study showed both RTG-Nanosuspension and drug dispersion were safe for i.n. delivery. An in vivo study showed that optimized RTG-Nanosuspension helped target RTG to the brain following i.n. administration. Overall, the RTG-Nanosuspension formulation showed potential in nose-to-brain delivery for targeted application in Parkinson's disease.Item (Re)Formulating rotigotine: a potential molecule with unmet needs(Future Science Group, 2023-01) Pandey, Murali Monohar; Chitkara, DeepakRotigotine (RTG), a non-ergoline D3/D2/D1 dopamine receptor agonist, is indicated for Parkinson’s disease (PD) and restless leg syndrome (RLS)[1]. It also has an affinity toward serotonin (5-HT1A, 5-HT2B, and 5-HT7) and α2B-adrenergic receptors [2]. At present, RTG is commercially available as an extended-release transdermal patch since it shows poor oral bioavailability because of its extensive first-pass metabolism [3]. Although successfully marketed, RTG potential has not been fully utilized owing to the challenges and drawbacks associated with its delivery. For instance, the absolute bioavailability from the transdermal patch is reported to be only 37%. The absolute bioavailability of transdermal patches varies depending on its site of application [3]. Moreover, RTG forms crystals in the transdermal patch upon storage and shows variations in drug release and bioavailability as wellItem Self-Assembled Lecithin-Chitosan Nanoparticles Improved Rotigotine Nose-to-Brain Delivery and Brain Targeting Efficiency(MDPI, 2023-03) Chitkara, Deepak; Pandey, Murali MonoharRotigotine (RTG) is a non-ergoline dopamine agonist and an approved drug for treating Parkinson’s disease. However, its clinical use is limited due to various problems, viz. poor oral bioavailability (<1%), low aqueous solubility, and extensive first-pass metabolism. In this study, rotigotine-loaded lecithin-chitosan nanoparticles (RTG-LCNP) were formulated to enhance its nose-to-brain delivery. RTG-LCNP was prepared by self-assembly of chitosan and lecithin due to ionic interactions. The optimized RTG-LCNP had an average diameter of 108 nm with 14.43 ± 2.77% drug loading. RTG-LCNP exhibited spherical morphology and good storage stability. Intranasal RTG-LCNP improved the brain availability of RTG by 7.86 fold with a 3.84-fold increase in the peak brain drug concentration (Cmax(brain)) compared to intranasal drug suspensions. Further, the intranasal RTG-LCNP significantly reduced the peak plasma drug concentration (Cmax(plasma)) compared to intranasal RTG suspensions. The direct drug transport percentage (DTP (%)) of optimized RTG-LCNP was found to be 97.3%, which shows effective direct nose-to-brain drug uptake and good targeting efficiency. In conclusion, RTG-LCNP enhanced drug brain availability, showing the potential for clinical application.