Formulation and Evaluation of In Situ Gelling Systems for Intranasal Administration of Gastrodin
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Gastrodin is the major bioactive constituent of the traditional Chinese drug “Tianma.” It is used in the treatment of some nervous system diseases and can be transported to the brain via intranasal administration. In the current paper, the development of a novel ion-activated in situ gelling system for the nasal delivery of gastrodin is discussed. An in situ perfusion model was used to determine the absorption-rate constant of gastrodin through rat nasal mucosa. The optimal formulation was determined by measuring the critical cation concentration, anti-dilution capacity, gel expansion coefficient, water-holding capacity, and adhesive capacity. The best formulation consisted of 10% gastrodin, 0.5% deacetylated gellan gum as the gelatinizer, and 0.03% ethylparaben as the preservative. The rheological properties of gastrodin nasal in situ gels were also investigated. The viscosity and elasticity sharply increased at temperatures below 25°C. When physiological concentrations of cations were added into the preparation, the mixture gelled into a semi-solid. The results of an accelerated stability test show that gastrodin nasal in situ gels can be stable for more than 2 years. Mucociliary toxicity was evaluated using the in situ toad palate model and the rat nasal mucociliary method; both models demonstrated no measurable ciliotoxicity. Pharmacodynamic studies suggest that similar acesodyne and sedative effects were induced following intranasal administration of 50 mg/kg gastrodin nasal in situ gels or oral administration of 100 mg/kg gastrodin solution. The in situ gel preparation is a safe and effective nasal delivery system for gastrodin.
KEY WORDSdeacetylated gellan gum gastrodin gelling system intranasal delivery ion-activated
This work was supported by the National Natural Science Foundation of China (no. 30902009) and Guangdong Natural Science Foundation (no. 10451008901004959).
- 2.Zhao H. Advance in clinical application of gastrodin. Strait Pharm J. 2009;21:29–31.Google Scholar
- 4.Guo Z, Tan T, Zhong Y, Wu C. Study of the mechanism of gastrodin and derivatives of gastrodigenin. J West Chin Univ Med Sci. 1991;22:79–82.Google Scholar
- 13.Funami T, Noda S, Nakauma M, Ishihara S, Takahashi R, Al-Assaf S, et al. Molecular structures of gellan gum imaged with atomic force microscopy in relation to the rheological behavior in aqueous systems in the presence or absence of various cations. J Agric Food Chem. 2008;56:8609–18.PubMedCrossRefGoogle Scholar
- 20.Tao T, Zhao Y, Yue P, Dong WX, Chen QH. Preparation of huperzine A nasal in situ gel and evaluation of its brain targeting following intranasal administration. Acta Pharm Sin. 2006;41:1104–10.Google Scholar
- 23.Jiang XG, Lu X, Cui JB, Qiu L, Xi NZ. Studies on octanol-water partition coefficient and nasal drug absorption. Acta Pharm Sin. 1997;32:458–60.Google Scholar