Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 576, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ijpharm.2020.119027
Keywords
Flunarizine hydrochloride; Organogel; Intraocular administration; Rheology; Cumulative release; Pharmacokinetic
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Funding
- Natural Science Foundation in Higher Education of Anhui Province [KJ2019A0454]
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We developed a safe and efficacious drug delivery system for treatment of brain diseases. A novel in-situ gel system was prepared using soybean oil, stearic acid and N-methyl-2-pyrrolidinone (NMP) (10:1:3, v/w/v). This system had low viscosity as a sol in vitro and turned into a solid or semi-solid gel in situ after administration. The poorly water-soluble drug flunarizine hydrochloride (FNZ) was incorporated into this organogel system. Organogel-FNZ was characterized by light microscopy, differential scanning calorimetry (DSC) and rheology. Drug release in vitro was investigated. The initial burst effect did not occur in organogel-FNZ, which is different from other gels formed in situ. Pharmacokinetic studies were undertaken in rats using gel administration (14 mg kg(-1)), intravenous administration (5 mg kg(-1)) and administration using drops (14 mg kg(-1)). Organogel-FNZ could reduce the clearance rate and prolong the duration of action, in the plasma and brain tissues of rats. The peak serum concentration, area under the curve and absolute bioavailability of the organogel-FNZ group were higher than those of the intraocular- drops group. Organogel-FNZ is a promising drug-delivery system for treatment of brain diseases by intraocular administration.
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