盐酸普拉克索亲水凝胶骨架缓释片的剂量倾泻研究

Dose Dumping Study for Pramipexole Hydrochloride Sustained Release Hydrophilic Matrix Tablets

关键词:  剂量倾泻  盐酸普拉克索缓释片  乙醇  羟丙甲纤维素  释放曲线

Key words:  dose dumping  pramipexole hydrochloride sustained release tablets  ethanol  HPMC  release profile

摘要:

目的 研究体外溶出释放条件对盐酸普拉克索亲水凝胶骨架缓释片释放的影响，并对其发生剂量倾泻的风险进行评估。方法 采用HPLC测定其在规定时间内不同水醇浓度介质以及不同转速下的累积释放度，并通过相似因子评价其与市售制剂Sifrol^®的相似度。结果 在pH 6.8 PBS介质中75，100和200 r·min^-1条件下以及在含5%，20%，40%乙醇的0.1 mol·L^-1盐酸介质中100 r·min^-1条件下，市售制剂与自制制剂在规定时间内的累积释放度相似。结论 不同水醇浓度介质以及不同转速对盐酸普拉克索亲水凝胶骨架缓释片体外的释放度影响不大，该处方发生剂量倾泻的风险可控。

Abstract:

OBJECTIVE To evaluate the effects of in vitro dissolution release conditions for pramipexole hydrochloride sustained release hydrophilic matrix tablets and conduct the risk assessment for the dose dumping. METHODS Different conditions such as different hydroalcohol concentration in the release media and rotation speed of paddle were evaluated. The cumulative drug release within the sepcified duration was determined by HPLC. The in vitro dissolution equivalence through profile comparison to the commercial product Sifrol^® was conducted using similarity factor method. RESULTS The cumulative release degree between the test and reference formulations under several conditions such as in pH 6.8 PBS media at 75, 100, 200 r·min^-1 and in the presence of 5%, 20% and 40% ethanol of 0.1 mol·L^-1 hydrochloric acid media at 100 r·min^-1 was similar. CONCLUSION There is little impact on the in vitro dissolution profile for pramipexole hydrochloride sustained release hydrophilic matrix tablets between various hydroalcohol concentrations and roation speed of paddle. The risk of dose dumping from the developed formulation is controllable.