Oral solid gentamicin preparation using emulsifier and adsorbent

Abstract

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™ US 2), 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 US 2, 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 US 2, 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 μg/ml) and AUC (4.74 ± 1.21 μg h/ml). Other preparations had C max and AUC of 0.69 ± 0.10 μg/ml and 1.56 ± 0.43 μg h/ml for Florite RE 20 mg, 1.07 ± 0.31 μg/ml and 1.80 ± 0.33 μg h/ml for Neusilin US 2, and 0.99 ± 0.21 μg/ml and 1.77 ± 0.50 μg 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 μg/ml and the AUC was 2.59 ± 0.33 μg h/ml). These results suggest that an adsorbent system is useful as an oral solid delivery system of poorly absorbable drugs such as GM.