论文部分内容阅读
Apomorphine-HCl is a potent D1 and D2 dopamine receptor agonist,which is effective in the treatment of Parkinsonism for on-offphenomenon.Currently available dosage form is only in injection form.Up oral administration,the drug is rapidly degraded in the gastrointestinal tract and subjected to a high first-pass effect,resulting in a lower bioavailability about 1.7%.Therefore we have designed an oral apomorphine-HC1 loaded solid lipid nanoparticles (SLN) which could be better tolerated.The formulation of solid lipid nanoparticles prepared with triglyceride,phospholipid and surfactant (hydrophobic and hydrophilic).The product of solid lipid nanoparticles contained apomorphine-HCl.Was evaluated by measuring the mean particle size,zeta potential,entrapment efficiency and stability in simulated gastrointestinal fluids.The optimization of solid lipid nanoparticles contained apomorphine-HCl was orally administrated into the rat model of Parkinson disease.The pharmacokinetics and phrmacodynamics of apomorphine SLN and control solution were evaluated in rat of Parkinson disease by oral administration of 20 mg/kg apomorphine.The AUC0-8 of apomorphine-SLN (238.61 ng-hr/mL) was higher than apomorphine-solution (20.4 ng-hr/mL).The mean contralateral rotation counts (109.25 counts) of apomorphine-SLN was higher than control solution (23.75 counts) at duration time.It proved that the treatment of Parkinson for on-off phenomenon was effective by oral administration of apomorphine-SLN dosage form.