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 (TM) RE), magnesium alminometa silicate (Neusilin (TM) USA and silicon dioxide (Sylysia (TM) 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 T-50% 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 mu g/ml) and AUC (4.74 +/- 1.21 mu g h/ml). Other preparations had C-max and AUC of 0.69 +/- 0. 10 mu g/ml and 1.56 +/- 0.43 mu g/ml for Florite RE 20 mg, 1.07 +/- 0.31 mu g/ml and 1.80 +/- 0.33 mu g/ml for Neusilin US2, and 0.99 +/- 0.21 mu g/ml and 1.77 +/- 0.50 mu g/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 mu g/ml and the AUC was 2.59 +/- 0.33 mu g/ml). These results suggest that an adsorbent system is useful as an oral solid delivery system of poorly absorbable drugs such as GM. (c) 2005 Elsevier B.V. All rights reserved.