Theeuwes F, Swanson D, Wong P, Bonsen P, Place V, Heimlich K, Kwan K C
J Pharm Sci. 1983 Mar;72(3):253-8. doi: 10.1002/jps.2600720313.
Based on the principles of an elementary osmotic pump, systems were designed to deliver indomethacin in solution at a constant rate, Z, to contain a total amount of drug, Mt, and to deliver 80% of their content at time t80. To allow selection of the optimal delivery rate into the body, three different prototypes were prepared with respective values for Z, Mt, and t80 of: 7 mg/hr, 85 mg, 11 hr; 9 mg/hr, 85 mg, 8 hr; and 12 mg/hr, 85 mg, 6 hr. These systems were found to deliver 70% of each system's contents at zero-order rates. Delivery rates were independent of pH, method of measurement, and stirring rate. In keeping with these results, the systems in the GI tract of dogs delivered at the same rate as in vitro, which qualifies the in vitro test as a bioanalogous method predictive of the in vivo performance of the dosage forms. Preliminary results in normal volunteers yielded similar urinary recoveries, while plasma profiles were different from each other and distinct from those following conventional capsules.
基于基本渗透泵原理，设计了一些系统，以恒定速率Z输送吲哚美辛溶液，使其含有总量为Mt的药物，并在时间t80时输送其80%的含量。为了选择进入体内的最佳给药速率，制备了三种不同的原型，其Z、Mt和t80的各自值分别为：7mg/小时、85mg、11小时；9mg/小时、85mg、8小时；以及12mg/小时、85mg、6小时。发现这些系统以零级速率输送每个系统70%的内容物。给药速率与pH值、测量方法和搅拌速率无关。与这些结果一致，狗胃肠道中的系统与体外给药速率相同，这使得体外试验成为一种可预测剂型体内性能的生物类似方法。正常志愿者的初步结果显示尿回收率相似，而血浆曲线彼此不同，且与服用传统胶囊后的曲线不同。
