Gastroretentive fibrous dosage forms for prolonged delivery of sparingly-soluble tyrosine kinase inhibitors. Part 4: Experimental validation of the models of drug concentration in blood

Abstract

In this final part, the models of drug concentration in blood developed in Part 3 are validated on dogs. Both 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 hours. The expanded dosage form fractured after 10 hours, and then passed into the intestine. 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 hours. By contrast, after administering the immediate-release particulate dosage form 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 hours. The experimental data validate the theoretical models reasonably. Thus, upon repeated dosing, the gastroretentive fibrous dosage forms presented in this study enable a constant drug concentration in blood for enhancing the efficacy and mitigating side effects of cancer therapies.