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http://hdl.handle.net/10603/386557
Title: | Development and Characterization of Lurasidone Hydrochloride Intranasal Nanoparticulate Drug Delivery System for Brain Delivery |
Researcher: | Annu |
Guide(s): | Ali, Javed and Baboota, Sanjula |
Keywords: | Clinical Pre Clinical and Health Pharmacology and Pharmacy Pharmacology and Toxicology |
University: | Jamia Hamdard University |
Completed Date: | 2022 |
Abstract: | Lurasidone hydrochloride (LH) suffers from poor aqueous solubility and low oral newlinebioavailability which warrants increase of LH doses causing toxicity to normal tissues. newlineTherefore, the current research focused on curtailing the inherent issues of LH by formulating newlineits nanoparticles (NPs) and their conjugation via transferrin (Tf). Chitosan (CH)-NPs were newlineprepared via ionic gelation technique and then optimized using QbD approach. The optimized newlineNPs were further to Tf conjugation via thiolation technique and further prepared using ionic newlinegelation method. The prepared NPs were analyzed for in vitro drug release and in vivo brain newlinetargeting efficiency. newlineChitosan NPs and Tf-conjugated CH-NPs exhibited mean particle size (154.8±4.5 nm; 207.1± newline5.43 nm), mean polydispersity index (0.433± 34.5; 0.411 ± 0.065); % EE (88.5± 0.05; 87.6 ± newline0.06); and % DLC (8.8±0.07; 7.6 ± 0.054) respectively. Transmission electron microscopy newlineexaminations revealed spherical particle size with uniform drug distribution. Physicochemical newlinestability of CH-NPs conducted for 12 weeks and showed good stability at (25 ± 2 °C/60 ± 5% newlineRH). DSC thermogram indicated the complete dispersion of drug within the nanoparticles newlineattributable to the loss of crystallinity of LH. FTIR spectra of NPs showed existence of Tf at newlineNPs surface confirming the conjugation of Tf. CH-NPs and Tf-conjugated NPs of LH showed newlineabsence of drug characteristics diffraction peaks indicating loss of crystallinity due to newlineentrapment of drug within the NPs. In vitro release studies established supremacy of LH-CHNPs newlineand Tf-conjugated CH-NPs compared to drug suspension (LH-DS) with cumulative drug newlinerelease of 85.83% and 89.34 ± 5.65 at pH 7.4 and 89.93±3.78% and 91.93 ± 5.67 at pH 6.4 newlinerespectively. Ex vivo nasal permeation studies revealed a 2.5-fold and 2.7-fold higher nasal newlinepermeation of LH from CH-NPs and Tf-conjugated CH-NPs formulation respectively newlinecompared to DS. Confocal microscopy evinced deeper permeation of Tf-conjugated CH-NPs newline(25 and#956;m), and CH-NPs (20 and#956;m) through nasal mucosa in contrast |
Pagination: | xviii, 146 |
URI: | http://hdl.handle.net/10603/386557 |
Appears in Departments: | Department of Pharmaceutics |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
01_title.pdf.pdf | Attached File | 53.09 kB | Adobe PDF | View/Open |
02_certificate.pdf.pdf | 110.84 kB | Adobe PDF | View/Open | |
03_preliminary pages.pdf.pdf | 373.08 kB | Adobe PDF | View/Open | |
04_chapter 1.pdf.pdf | 348.99 kB | Adobe PDF | View/Open | |
05_chapter 2.pdf.pdf | 187.01 kB | Adobe PDF | View/Open | |
06_chapter 3.pdf.pdf | 185.83 kB | Adobe PDF | View/Open | |
07_chapter 4.pdf.pdf | 333.76 kB | Adobe PDF | View/Open | |
08_chapter 5.pdf.pdf | 2.42 MB | Adobe PDF | View/Open | |
09_chapter 6.pdf.pdf | 708.85 kB | Adobe PDF | View/Open | |
10_bibliography.pdf | 169.85 kB | Adobe PDF | View/Open | |
11_appendices.pdf.pdf | 558.92 kB | Adobe PDF | View/Open | |
80_recommendation.pdf | 751.2 kB | Adobe PDF | View/Open | |
abstract.pdf.pdf | 160.46 kB | Adobe PDF | View/Open |
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