醋氨酚缓释包衣颗粒研究

包衣颗粒体外溶出试验证明在释放量达66%以前为零级恒速释放,此后释放速率降低为非零级释放。颗粒在室温下密闭贮存21个月后,释放速率增快,但仍为零级释放,也是在释放量达66%以后转变为非零级释放。用尿药排泄速率法研究了包衣颗粒的体内动力学并与常规片剂作比较,并测出两者的消除速率常数。常规片剂所得药物t 1/2=3.21h,而包衣颗粒剂所得半衰期约延长2.5倍。通过吸收百分率与体外溶出百分率在不同时间下数值的比较得到线性关系,相关系数r=0.9886。说明体外溶出数据可以作为控制吸收率的依据。按一级吸收一室模型公式计算了一定剂量下的血药浓度,在13h以内血药浓度都在治疗浓度范围(5～20μg/ml)以内。最高浓度为10.5μg/ml,达峰时间为3.27h。本品一次服1.1g可延效12h。

STUDIES ON THE CONTROLLED RELEASE OF ACETAMINOPHEN FROM COATED GRANULES

Acetaminophen is one of the most important non-steriodal anti-inflammatory drugs currently used in clinics. However, its short half-life and frequency of administration made it inconvenient for patients, so there is a need to search for new preparations which may be taken not more than once or twice a day. We prepared coated granules by fluidize-coating method.In in vitro dissolution study, zero order release was observed up to the time when 66% was released. After that, non-zero order release followed, when the rate decressed quickly with time. The absorption and excretion rates were determined by analysing the total amount of acetaminophen and its metabolites in the urine collected at different intervals.It was found that the apparent half-life was prolonged to 8.29 h by oral administration of the coated granules. Using the parameters, the blood concentrations were calculated at different times after oral administration of 1.1 g of coated granules. From the data, it appears reasonable to expect to keep the blood level within the effective therapeutic window of the drug for 12 h by a dose of 1.1 g of the coated granule.