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Preparation of nimodipine-loaded microemulsion for intranasal delivery and evaluation on the targeting efficiency to the brain.

Abstract：

:The purpose of this study was to improve the solubility and enhance the brain uptake of nimodipine (NM) in an o/w microemulsion, which was suitable for intranasal delivery. Three microemulsion systems stabilized by the nonionic surfactants either Cremophor RH 40 or Labrasol, and containing a variety of oils, namely isopropyl myristate, Labrafil M 1944CS and Maisine 35-1 were developed and characterized. The nasal absorption of NM from microemulsion formulation was investigated in rats. The optimal microemulsion formulation consisted of 8% Labrafil M 1944CS, 30% Cremophor RH 40/ethanol (3:1) and water, with a maximum solubility of NM up to 6.4 mg/ml, droplet size of 30.3 +/- 5.3 nm, and no ciliotoxicity. After a single intranasal administration of this preparation at a dose of 2 mg/kg, the plasma concentration peaked at 1 h and the absolute bioavailability was about 32%. The uptake of NM in the olfactory bulb from the nasal route was three folds, compared with intravenous (i.v.) injection. The ratios of AUC in brain tissues and cerebrospinal fluid to that in plasma obtained after nasal administration were significantly higher than those after i.v. administration. These results suggest that the microemulsion system is a promising approach for intranasal delivery of NM for the treatment and prevention of neurodegenerative diseases.

journal_name

Int J Pharm

journal_title

International journal of pharmaceutics

authors

Zhang Q,Jiang X,Jiang W,Lu W,Su L,Shi Z

doi

10.1016/j.ijpharm.2004.01.039

keywords:

subject

Has Abstract

pub_date

2004-05-04 00:00:00

pages

85-96

issue

1-2

eissn

0378-5173

issn

1873-3476

pii

S0378517304000870

journal_volume

275

pub_type

杂志文章

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