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Development and Evaluation of a Novel Intranasal Spray for the Delivery of Amantadine

Lungare, Shital; Bowen, James and Badhan, Raj (2016). Development and Evaluation of a Novel Intranasal Spray for the Delivery of Amantadine. Journal of Pharmaceutical Sciences, 105(3) pp. 1209–1220.

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URL: http://www.sciencedirect.com/science/article/pii/S...
DOI (Digital Object Identifier) Link: https://doi.org/10.1016/j.xphs.2015.12.016
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Abstract

The aim of this study was to develop and characterise an intranasal delivery system for amantadine (AMT). Optimal formulations (F) consisted of a thermosensitive polymer Pluronic® 127 (P127) and either carboxy methyl cellulose (CMC) or chitosan (CS) which demonstrated gel-transition at nasal cavity temperatures (34 °C ± 1 °C). Rheologically, the loss tangent (Tan δ) confirmed a three-stage gelation phenomena at 34 °C ± 1 °C and non-Newtonian behaviour. Storage of FCMC and FCS at 4 °C for 8 weeks resulted in repeatable release profiles at 34 °C when sampled, with a Fickian mechanism earlier on but moving towards anomalous transport by week 8. Polymers (P127, CMC and CS) demonstrated no significant cellular toxicity to human nasal epithelial cells up to 4 mg/mL and up to 1 mM for AMT (IC50: 4.5 mM ± 0.05 mM). FCMC and FCS demonstrated slower release across an in-vitro human nasal airway model (43-44 % vs 79 % ± 4.58 % for AMT). Using a human nasal cast model, deposition into the olfactory regions (potential nose-to-brain) was demonstrated upon nozzle insertion (5 mm) whereas tilting of the head forward (15°) resulted in greater deposition in the bulk of the nasal cavity.

Item Type: Journal Item
Copyright Holders: 2016 American Pharmacists Association
ISSN: 1520-6017
Keywords: Parkinson's disease; rheology; nasal; RPMI 2650; nose to brain; thermoresponsive
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Engineering and Innovation
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Item ID: 45741
Depositing User: James Bowen
Date Deposited: 22 Mar 2016 15:42
Last Modified: 13 Nov 2016 06:19
URI: http://oro.open.ac.uk/id/eprint/45741
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