Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2506779 | International Journal of Pharmaceutics | 2006 | 6 Pages |
Oral anticoagulant therapy with heparin has been challenged by formulating heparin in oral solid preparation. As heparin, low molecular weight heparin (LMWH) was used. LMWH was dispersed with a surfactant used for the self-microemulsifying drug delivery system (SMEDDS), PEG-8 caprylic/capric glycerides (Labrasol), and the mixture was solidified with three kinds of adsorbents, microporous calcium silicate (Florite™ RE), magnesium alminometa silicate (Neusilin™ US2) and silicon dioxide (Sylysia™ 320). The in vitro release study showed that the T50%s were 3.2 ± 0.1 min for Sylysia 320, 4.6 ± 0.2 min for Florite RE, 13.7 ± 0.1 min for Neusilin US2. The in vivo rat absorption study showed that Florite RE system had the highest Cmax, 0.42 ± 0.01 IU/mL and AUC, 0.59 ± 0.06 IU h/mL, where plasma LMWH levels were measured as anti-Xa activity. Other preparations had the Cmax and AUC, 0.12 ± 0.01 IU/mL and 0.15 ± 0.02 IU h/mL for Neusilin US2 and 0.25 ± 0.02 IU/mL and 0.40 ± 0.03 IU h/mL for Sylysia 320, respectively. The bioavailability (BA) of LMWH from the microporous calcium silicate preparation, Florite RE, was 18.8% in rats by comparing the AUC obtained after i.v. injection of LMWH, 40 IU/kg to another group of rats. Florite RE system was evaluated in dogs after oral administration in an enteric capsule made of Eudragit S100 at the LMWH dose of 200 IU/kg. High plasma anti-Xa activity levels were obtained, i.e., the Cmax was 0.48 ± 0.11 IU/mL and AUC was 1.64 ± 0.32 IU h/mL. These results suggest that adsorbent system is useful as an oral solid delivery system of poorly absorbable drugs such as LMWH.