The effect of a semi-permeable, strengthening fiber coating on the expansion, mechanical properties, and residence time of gastroretentive fibrous dosage forms

Recently, we have shown in dogs that the gastric residence time of expandable fibrous dosage forms can be prolonged by coating the fibers with a semi-permeable, strengthening coating. In this work on pigs, the effect of the volume fraction of the coating, φc , on the expansion, mechani...
Ausführliche Beschreibung

Recently, we have shown in dogs that the gastric residence time of expandable fibrous dosage forms can be prolonged by coating the fibers with a semi-permeable, strengthening coating. In this work on pigs, the effect of the volume fraction of the coating, φc , on the expansion, mechanical strength, and gastric residence time is investigated. Three methacrylic acid-ethyl acrylate-coated fibrous dosage forms with φc  = 0.025, 0.041, and 0.068 were prepared and tested. Upon administering to a pig, the dosage forms expanded to a normalized radial expansion of 0.5–0.6 in 5, 8, and 10 h, respectively. The expanded dosage forms resided in the stomach and fragmented after 11, 25, and 31 h. The fragments then passed into the intestines and dissolved in 2–3 h. Models suggest that upon contact with gastric fluid, a hydrostatic pressure develops in the fibers due to the inward diffusion of water. The hydrostatic pressure in turn induces a tensile stress in the coating and the dosage form expands. The tensile stress and the expansion rate are inversely proportional to φc . The expanded dosage form eventually fractures due to the loads applied by the contracting stomach walls. The post-expansion mechanical strength and the time to fracture increase steeply with φc . The models predict the experimental results reasonably well. Thus, by increasing φc , dosage form fracture is delayed and the gastric residence time prolonged. Ausführliche Beschreibung