Study On The Drug Delivery System Of Nasal Mucosal Of Pramipexole Microcapsules With Temperature Sensitive Gel

Objective:Pramipexole Hydrochloride is a non-ergot-based selective dopamine receptor agonist that is currently used to treat Parkinson’s disease.Pramipexole hydrochloride has many problems such as daily taking times,fluctuation of peak and valley.In this study,pramipexole hydrochloride is made into temperature-sensitive microcapsule gel,which is administered by nasal mucosa to achieve sustained-release effect,thereby improving patient compliance and reducing peak-valley fluctuation.Methods:The microcapsules of pramipexole hydrochloride were prepared by emulsifying solvent evaporation method.,the drug loading and in vitro cumulative release rate were used as the evaluation indexes to select the capsule;The drug loading rate and the cumulative permeation rate in vitro were used to evaluate the prescription proportion.The temperature sensitive in situ gel was prepared by cold method,the content of gel matrix was determined by the gel temperature(Tgel)and the amount of gel dissolution.;Adhesive strength was selected as the evaluation index;Screening of absorption enhancers with the cumulative drug permeation as the evaluation index.The quality was evaluated by percentage of drug,gel temperature,time,pH,viscosity,spreadability,adhesive strength,membrane dissolution and in vitro permeation,and pharmacokinetic study of thermosensitive microcapsule gel was carried out with rat as experimental animal.Results:Polyacrylic acid resin,Span-80 and pramipexole hydrochloride ratio of(20:3:10)poloxamer 407,poloxamer 188,borneol,carbomer,ethyl paraben and ascorbic acid ratio of(24:6:0.3:0.45:2:1),and drug-containing gel percentage range 0%-8%,gelling temperature(30.90±0.46)℃,time(39.33±2.06)s,pH(3.39±0.01),viscosity(241.50±2.50)mpa.s,spreadability(6.40±0.13)cm,adhesion strength(2 727.67±0.17)dynes·cm-2,12 h filmless dissolution of the drug release(78.50±4.20)%,gel dissolution(26.80±0.90)%,12 h drugs through in vitro 410.60±4.50)μg·cm-2.Pharmacokinetic experiments with pramipexole-sensitive microcapsules at 2 h in the brain drug concentration reached the maximum(0.29±0.10)μg·mL-1,while poprazole hydrochloride drug 1 h in the brain when the maximum concentration of drugs(0.17±0.10)μg·mL-1.Conclusions:The temperature-sensitive microcapsule gel of pramipexole hydrochloride was prepared by the method of emulsifying solvent evaporation and cooling,the preparation process was simple,it was optimized,and the basic properties(percentage of drug,gel temperature,time,pH,viscosity,spreadability,adhesion strength,membrane dissolution and in vitro penetration)were investigated.And by pharmacokinetic studies,pramipexole hydrochloride microencapsulated gel can achieve sustained release compared with the original drug and improve patient compliance.