title: Formulation and evaluation of in situ gelling systems for intranasal administration of gastrodin.
abstract: 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.
authors: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
authors: Zheng
authors: Z
authors: Cai
authors: Xiangrong
authors: X
authors: Song
authors: Feng
authors: F
authors: Sun
authors: Zhaoxiang
authors: Z
authors: Yang
authors: Shixiang
authors: S
authors: Hou
authors: Zhongqiu
authors: Z
authors: Liu
mesh_terms: D000042:Absorption; D019342:Acetic Acid; D000268:Adhesiveness; D000281:Administration, Intranasal; D000818:Animals; D001001:Anura; D001592:Benzyl Alcohols / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D002626:Chemistry, Pharmaceutical; D004195:Disease Models, Animal; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D004548:Elasticity; D005782:Gels; D005960:Glucosides / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D008297:Male; D009297:Nasal Mucosa / Q000378:metabolism; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control; D010226:Parabens / Q000737:chemistry; D010539:Permeability; D011135:Polysaccharides, Bacterial / Q000737:chemistry* / Q000633:toxicity; D011310:Preservatives, Pharmaceutical / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012212:Rheology; D012890:Sleep / Q000187:drug effects; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature; D013997:Time Factors; D014783:Viscosity; D014867:Water / Q000737:chemistry
chemical_list: D001592:Benzyl Alcohols; D004337:Drug Carriers; D004365:Drugs, Chinese Herbal; D005782:Gels; D005960:Glucosides; D010226:Parabens; D011135:Polysaccharides, Bacterial; D011310:Preservatives, Pharmaceutical; D014867:Water; C012313:ethyl-p-hydroxybenzoate; C045345:gastrodin; C048288:gellan gum; D019342:Acetic Acid