The release rate and simulation of heparin-filled hollow fiber patch

Abstract

Purpose: To develop a new drug delivery system made of hollow fiber fabric. We report preliminary in-vitro results of heparin-impregnated hollow fiber and simulation of local in-vivo concentration. Methods: A knitted patch (5 × 30 mm) made of Dacron hollow fiber (T-334W, 1 hole with 15% void, 5.5 Denier per filament,) was impregnated with 10,000 IU/3 ml of Fragmin using a vacuum chamber. The infused patch was placed in 50 ml distilled water and the conductivity was measured over 4 weeks. The release rate of Fragmin from the patch was estimated using the compartmental modeling software SAAMII. We simulated the time course of heparin concentration in human plasma for the following: 1) whole-body heparin concentration following a constant infusion of 1000 IU heparin/hour, 2) whole-body heparin concentration following the release of heparin from a 8×70 mm heparin-infused hollow fiber patch, 3) local concentration (over 5 ml blood) following the same heparin-infused patch. Results: Release rate of Fragmin from the 5 × 30mm patch is estimated to be proportional to the amount of heparin in the patch with a constant of proportion 0.3444 (SD 0.05). The simulated local concentration of Fragmin released by the 5 × 70 mm patch impregnated in 20000IU/ml solution remains higher than that of a constant infusion for up to 2 days. Systemic concentration resulting from the patch is negligible. Conclusions: Fragmin was released continuously from the hollow fiber fabric models for more than 2 weeks. The simulation demonstrates that local concentration resulting from the patch remains higher than that of constant infusion for up to 2 days, and argues that a hollow fiber patch is an effective method for localized delivery of heparin.