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 a strengthening enteric coating on the fibers. In this work, the effect of the volume fraction of the coating, φc, on the expansion, mechanical properties, and gastric residence time in pigs 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 normalized radial expansion of the dosage forms was 0.5-0.6 in 5, 8, and 10 hours. The expanded dosage forms were retained in the stomach for 11, 25, and 31 hours. Thereafter, they fragmented; the fragments passed into the intestines and dissolved in 2-3 hours. Models suggest that upon contact with gastric fluid, a hydrostatic pressure develops in the fibers due to osmosis, which in turn induces a tensile stress in the coating, and causes the coating and dosage form to expand. The expansion rate is inversely proportional to the coating thickness or volume fraction. Diametral compression tests show that immediately after expansion the fracture strength of the dosage forms is greater than the stress due to the loads applied by the contracting stomach walls. But because the fracture strength decreases with soaking time, in the stomach the dosage form fractures eventually. The time to fracture increases with φc. Thus, by varying φc, the expansion rate and mechanical properties of the fibrous dosage forms can be readily optimized to control gastric residence time.