Halsas M, Ervasti P, Veski P, Jürjenson H, Marvola M
Department of Pharmacy, University of Helsinki, Finland.
Eur J Drug Metab Pharmacokinet. 1998 Apr-Jun;23(2):190-6. doi: 10.1007/BF03189338.
This paper deals with press-coated modified release tablets in which the drug dose is situated in the core or is divided between the core and the coat. The coat contains polymer (sodium alginate or hydroxypropylmethyl cellulose, HPMC) to control drug release. The main objective was to investigate how the pharmacokinetic profile of the model drug could be modified by altering the proportion of the drug between the core and the coat. The effect of the amount of the polymer in the coat was also studied. Bioavailability tests were carried out on healthy volunteers. In the absorption curves of the tablets containing 50%, 67% and 80% of the drug in the core and 180 mg HPMC in the coat a bimodal profile was observed. No bimodal release pattern in the in vitro dissolution studies was found. If the whole dose was incorporated in the core the absorption curve has only one clear t(max) value at about 10 h. Doubling the amount of HPMC in the coat dramatically decreased drug absorption. It was concluded that, if a slightly reduced t(max)-value was required, the viscosity grade of HPMC used should be lowered.
本文涉及压制包衣的缓释片，其中药物剂量位于片芯中或在片芯与包衣之间分配。包衣含有聚合物（海藻酸钠或羟丙基甲基纤维素，HPMC）以控制药物释放。主要目的是研究如何通过改变片芯与包衣之间药物的比例来改变模型药物的药代动力学特征。还研究了包衣中聚合物用量的影响。对健康志愿者进行了生物利用度测试。在片芯中含有50%、67%和80%药物且包衣中含有180mg HPMC的片剂的吸收曲线中观察到双峰特征。在体外溶出研究中未发现双峰释放模式。如果将全部剂量都加入片芯中，吸收曲线在约10小时处只有一个明显的t(max)值。将包衣中HPMC的量加倍会显著降低药物吸收。得出的结论是，如果需要略微降低t(max)值，应降低所用HPMC的粘度等级。
