阿司匹林缓释片的研制及药代动力学

 目的：制备阿司匹林缓释片，评价人体内动力学、相对生物利用度及血药浓度。方法：以羟丙甲纤维素，聚丙烯酸树脂Ⅱ为释放阻滞剂制备缓释片，转篮法测释放度，高效液相色谱法测10名男性健康志愿者交叉po 50mg肠溶片和缓释片后的血药浓度，数据经3P87软件微机处理。结果：体外释药：肠溶片t₅₀=2.4h，缓释片t₅₀=4.5h。释药9h以上。单剂量 po 加肠溶片和缓释片c_max分别为(7.96士1.65)μg·ml^-1和(3.03士0.22)μg·ml^-1(P<0.01)。t_1/2R分别为(2.89士0.93)h和(7.81士2.16)h。(P<0.01)。AUC_o～２4h为(64.53土8.86)μg·h·ml^-1和(66.49士12.55)μg·h·ml^-1(P>0.05)，相对生物利用度为(103.49士12.32)%。多剂量po加肠溶片和缓释片。C_min分别为(0.54士0.20)μg·ml^-1和(1.25士0.27)μg·ml^-1(P<0.01)0。分别为(6.86士1.09)μg·ml^-1和(3.29士0.41)μg·ml^-1(P<0.01)。FI分别为(1.73士0.16)和(0.86士0.23)(P<0.01)。结论：该缓释片处方合理，工艺简单，适合于工业化生产，为预防和治疗血栓形成提供一个新的剂型。

Studies on preparation,release and pharmacokinetics of aspirin sustained release tablets

OBJECTIVE:To prepare aspirin sustained release tablets and study the pharmacokinetics and relative bioavailability in volunteers. METHODS:Hypromellose and poplyacrglic resin Ⅱ were used as blocking agent for the preparation of sustained-release tablets.The release experiments were performed in a rotating shaker.The aspirin in concentrations in serum were assayed by HPLC mothod.A single oral does of sustained-release tablets and enteric coated tablet were given to 10 volunteers respectively in an open randomized cross-over test.3P87 was used to process main pharmacokinetic parameters. RESULTS:The sustained-release of tablet and enteric coated tablets in vitro,t₅₀ was 4.5 h and 2.4 h respectively.The drug in sustained-release tablets was released over 9 h.The main parameters of daily dose were as following.c_maxof enteric tablets and sustained-release tablets were (7.96±1.65)μg·ml^-1and (3.03±0.22)μg·ml^-1(P＜0.01).t_1/2K(2.89±0.93) h and (7.81±2.16)h.(P＜0.01).AUC_0～24h(64.53±8.86)μg·h·ml^-1and (66.49±12.55)μg·h·ml^-1(P＞0.05).The relative bioavailability of sustained-release tablets was (103.49±12.32)%.The main parameters of cumulative dose in body,c_minof enteric coated tablets and sustained-release tablets were (0.54±0.20)μg·ml^-1and (125±0.27)μg·ml^-1(P＜0.01)。c_max(6.86±1.09)μg·ml^-1and (3.29±0.41)μg·ml^-1(P＜0.01)。FI(1.73±0.16) and (0.86±0.23),respectively (P＜0.01). CONCLUSION:The sustained-release tablets may play an important role in prevention and treatment of thrombogenesis as the result of its reasonable formulation and simple technology.