%0 Journal Article
%T Gastroretentive fibrous dosage forms for prolonged delivery of sparingly-soluble tyrosine kinase inhibitors. Part 3: Theoretical models of drug concentration in blood.
%A Blaesi AH
%A Saka N
%J Int J Pharm
%V 0
%N 0
%D 2024 Jun 18
%M 38901538
%F 6.51
%R 10.1016/j.ijpharm.2024.124362
%X In this part, drug concentration in blood after ingesting slow-release gastroretentive fibrous dosage forms and immediate-release particulate forms is modeled. The tyrosine kinase inhibitor nilotinib, which is slightly soluble in low-pH gastric fluid but practically insoluble in pH-neutral intestinal fluid is used as drug. The models suggest that upon ingestion, the fibrous dosage form expands, is retained in the stomach for prolonged time, and releases drug into the gastric fluid at a constant rate. The released drug molecules flow into the duodenum with the gastric fluid, and are absorbed by the blood. The drug is eliminated from the blood by the liver at a rate proportional to its concentration. Eventually, the elimination and absorption rates will be equal, and the drug concentration in blood plateaus out. After the gastric residence time drug absorption stops, and the drug concentration in blood drops to zero. By contrast, after administering an immediate-release particulate dosage form the drug particles are swept out of the stomach rapidly, and drug absorption stops much earlier. The drug concentration in blood rises and falls without attaining steady state. The gastroretentive fibrous dosage forms enable a constant drug concentration in blood for drugs that are insoluble in intestinal fluids.