Study On Preparation Of Levodopa Gel For Nasal Administration And Its Tissue Distribution In Rabbit Brain

Objective Levodopa-2,6-Dimethyl- β - cyclodextrin(DM- β -CD) gel was prepared fornasal administration. We expect that levodopa-DM- β -CD has better fatsoluble thanlevodopa, easy to permeate through the nasal mucous membrane & the olfactory nerve cell in nasal cavity, gets to the brain tissue brings into play its therapeutic action, and lessen its side effects by reduce the dopamine content in peripheral blood.Methods Levodopa-DM- β -CD was prepared with DM- β -CD by saturation solution,ultrasonic, and grinding methods. The best inclusion technology was screened out with orthogonal design by the alteration of the experimental conditions, such as temperature, stirspeed, and ratio of levodopa to DM- β -CD. Used the above-mentioned inclusion complex(Levodopa-DM- β -CD ), levodopa nasal administration gel was prepared with orthogonaldesign by the alteration of the ratio of pharmaceutical aids, and the technology conditions. Rabbits were administrated with the above levodopa gel through nasal cavity, we determined the contents of levodopa in rabbit brain, levodopa oral tablet was administrated for positive contrast.Results The yield and content of levodopa inclusion complex prepared by the saturation solution method were 78.21% and 15.49% respectively, the inclusion conditioninvolved that the mol ratio of levodopa to DM- β -CD was 1:1, stir temperature was 60℃,inclusion time was 4 hours, and stir speed was 300 rpm. The ratio of nasal gel formation included 12% levodopa inclusion complex, 3%carbomer 941, 15% Potyoxyethylene Castoroil ether, 5% HP— ft -CD, 0.2% Sodium Benzoate. The accumulated release in vitro oflevodopa from the gel was 50% at the No.6 hour. Levodopa inclusion complex was easier to be absorbed and distributed into brain by permeation the nasal mucous membrane than the levodopa oral tablet, on the condition of same dosage administration, the levodopa concentrations of inclusion coplex and levodopa oral tablet in rabbit brain were4.38+0.62u￡/g |P 0.71±0.19f.ig/g respectively.Conclusions Levodopa gel was prepared with levodopa-DM- ft -CD, easier to be absorbed and distributed into rabbit brain through nasal mucous membrane than oral tablets administration, the levodopa concentration in rabbit brain tissue of gel was 5-9 times higher than tablets. .