Tomohiro Kusawake | PubMed Health

PubMed2006

Preparation and evaluation of oral solid heparin using emulsifier and adsorbent for in vitro and in vivo studies.

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 US(2)) and silicon dioxide (Sylysia 320). The in vitro release study showed that the T50%s were 3.2+/-0.1min for Sylysia 320, 4.6+/-0.2min for Florite RE, 13.7+/-0.1min for Neusilin US(2). The in vivo rat absorption study showed that Florite RE system had the highest C(max), 0.42+/-0.01IU/mL and AUC, 0.59+/-0.06IUh/mL, where plasma LMWH levels were measured as anti-Xa activity. Other preparations had the C(max) and AUC, 0.12+/-0.01IU/mL and 0.15+/-0.02IUh/mL for Neusilin US(2) and 0.25+/-0.02IU/mL and 0.40+/-0.03IUh/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, 40IU/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 200IU/kg. High plasma anti-Xa activity levels were obtained, i.e., the C(max) was 0.48+/-0.11IU/mL and AUC was 1.64+/-0.32IUh/mL. These results suggest that adsorbent system is useful as an oral solid delivery system of poorly absorbable drugs such as LMWH.

Administration, Oral↗

PubMed2005

Oral solid gentamicin preparation using emulsifier and adsorbent.

Oral gentamicin (GM) therapy has been challenged by formulating GM in oral solid preparation. GM 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 several kinds of adsorbents. The used adsorbents were microporous calcium silicate (Florite RE), magnesium alminometa silicate (Neusilin US2), and silicon dioxide (Sylysia 320). In vitro release study showed that the percentage released of GM from each preparation per 2 h was 99.8+/-0.06% for Florite RE 10 mg, 96.7+/-1.16% for Florite RE 20 mg, 98.3+/-0.32% for Neusilin US2, and 94.4+/-0.23% for Sylysia 320. The T50% values were 0.35+/-0.05 h for Florite RE 10 mg, 0.34+/-0.03 h for Florite RE 20 mg, 0.26+/-0.03 h for Neusilin US2, and 0.15+/-0.01 h for Sylysia 320. The in vivo rat absorption study showed that Florite RE 10 mg preparation had the highest C(max) (2.14+/-0.67 microg/ml) and AUC (4.74+/-1.21 microg h/ml). Other preparations had C(max) and AUC of 0.69+/-0.10 microg/ml and 1.56+/-0.43 microg h/ml for Florite RE 20 mg, 1.07+/-0.31 microg/ml and 1.80+/-0.33 microg h/ml for Neusilin US2, and 0.99+/-0.21 microg/ml and 1.77+/-0.50 micorg h/ml for Sylysia 320, respectively. The bioavailability (BA) of GM from the microporous calcium silicate preparation, Florite RE 10 mg, was 14.1% in rats, derived by comparing the AUC obtained after intravenous injection of GM, 1.0 mg/kg, to another group of rats. The microporous calcium silicate preparation using Florite RE 10 mg was evaluated in dogs after oral administration in an enteric capsule, Eudragit S100 (50 mg/dog). High plasma GM levels were obtained (i.e., the C(max) was 1.26+/-0.20 microg/ml and the AUC was 2.59+/-0.33 microg h/ml). These results suggest that an adsorbent system is useful as an oral solid delivery system of poorly absorbable drugs such as GM.

Adsorption↗