Abstract：
In this final part, the models of drug concentration in blood developed in Part 3 are validated on dogs. Both slow-release gastroretentive fibrous and immediate-release particulate dosage forms containing 200 mg nilotinib were tested. After administering, the fibrous dosage form expanded linearly with time in the stomach, to about 1.5 times the initial radius by 4 h. The expanded dosage form fractured after 10 h, and then passed into the intestines. The drug concentration in blood exhibited a broad peak with a maximum of 0.51 μg/ml and a width at half-height of 10.2 h. By contrast, after administering the immediate-release capsule the drug concentration in blood exhibited a sharp peak with a maximum of 0.68 μg/ml and a width at half-height of just 3.6 h. The experimental data validate the theoretical models reasonably. The gastroretentive fibrous dosage forms designed in this study enable a steady drug concentration in blood for increasing the efficacy and mitigating side effects of drug therapies.
摘要：
在这最后一部分,第3部分开发的血液中药物浓度模型在狗上进行了验证。测试了含有200mg尼洛替尼的缓释胃滞留纤维和速释微粒剂型。管理后,纤维剂型在胃中随时间线性膨胀，到4小时时，约为初始半径的1.5倍。膨胀的剂型在10小时后破裂，然后进入肠道.血液中的药物浓度显示出一个宽峰，最大值为0.51μg/ml，半高宽度为10.2h。给药速释胶囊后，血液中的药物浓度出现一个尖峰，最大为0.68μg/ml，半高宽度仅为3.6h。实验数据合理地验证了理论模型。本研究中设计的胃滞留纤维剂型能够在血液中稳定的药物浓度，以增加疗效并减轻药物治疗的副作用。
