Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 1209-1220 |
| Number of pages | 12 |
| Journal | Journal of Pharmaceutical Sciences |
| Volume | 105 |
| Issue number | 3 |
| Early online date | 30 Jan 2016 |
| DOIs | |
| Publication status | Published - Mar 2016 |
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Bibliographical note
© 2016, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/Keywords
- Parkinson's disease
- rheology
- thermoresponsive
- nose to brain
- nasal
- RPMI 2650
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Development and evaluation of a novel intranasal spray for the delivery of amantadine. / Lungare, Shital; Bowen, James; Badhan, Raj.
In: Journal of Pharmaceutical Sciences, Vol. 105, No. 3, 03.2016, p. 1209-1220.Research output: Contribution to journal › Article
TY - JOUR
T1 - Development and evaluation of a novel intranasal spray for the delivery of amantadine
AU - Lungare, Shital
AU - Bowen, James
AU - Badhan, Raj
N1 - © 2016, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
PY - 2016/3
Y1 - 2016/3
N2 - 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.
AB - 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.
KW - Parkinson's disease
KW - rheology
KW - thermoresponsive
KW - nose to brain
KW - nasal
KW - RPMI 2650
UR - http://www.scopus.com/inward/record.url?scp=84964484018&partnerID=8YFLogxK
U2 - 10.1016/j.xphs.2015.12.016
DO - 10.1016/j.xphs.2015.12.016
M3 - Article
AN - SCOPUS:84964484018
VL - 105
SP - 1209
EP - 1220
JO - Journal of Pharmaceutical Sciences
JF - Journal of Pharmaceutical Sciences
SN - 0022-3549
IS - 3
ER -