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.

Abstract

The aim of this study was to develop and characterize an intranasal delivery system for amantadine hydrochloride (AMT). Optimal formulations consisted of a thermosensitive polymer Pluronic® 127 and either carboxymethyl cellulose or chitosan which demonstrated gel transition at nasal cavity temperatures (34 ± 1°C). Rheologically, the loss tangent (Tan δ) confirmed a 3-stage gelation phenomena at 34 ± 1°C and non-Newtonian behavior. Storage of optimized formulation carboxymethyl cellulose and optimal formulation chitosan at 4°C for 8 weeks resulted in repeatable release profiles at 34°C when sampled, with a Fickian mechanism earlier on but moving toward anomalous transport by week 8. Polymers (Pluronic® 127, carboxymethyl cellulose, and chitosan) 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 ± 0.05 mM). Optimized formulation carboxymethyl cellulose and optimal formulation chitosan 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 on nozzle insertion (5 mm), whereas tilting of the head forward (15°) resulted in greater deposition in the bulk of the nasal cavity.

Publication DOI: https://doi.org/10.1016/j.xphs.2015.12.016
Divisions: Life & Health Sciences > Pharmacy
Life & Health Sciences
Life & Health Sciences > Applied Health Research Group
Additional Information: © 2016, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Uncontrolled Keywords: Parkinson's disease,rheology,thermoresponsive,nose to brain,nasal,RPMI 2650,Pharmaceutical Science
Full Text Link:
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
Published Date: 2016-03
Authors: Lungare, Shital
Bowen, James
Badhan, Raj ( 0000-0002-0904-9324)

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